Publications by category
Journal articles
Sabatini S, Martyr A, Ukoumunne OC, Ballard C, Collins R, Pentecost C, Rusted JM, Quinn C, Anstey KJ, Kim S, et al (In Press). Attitudes Toward Own Aging and Cognition among Individuals Living with and without Dementia: Findings from the IDEAL Programme and the PROTECT Study.
Abstract:
Attitudes Toward Own Aging and Cognition among Individuals Living with and without Dementia: Findings from the IDEAL Programme and the PROTECT Study
Abstract
. Background: it is unclear whether people with dementia (PwD) have more negative attitudes toward own aging (ATOA) than people without dementia and what factors influence ATOA among PwD. We investigated whether PwD have more negative ATOA than individuals without dementia and whether cognition and dementia subtype are associated with ATOA in PwD.Methods: Data from the IDEAL and PROTECT studies were used to compare ATOA between 1,502 PwD (mean (SD) age = 76.3 (8.5)) and 6,377 individuals without dementia (mean (SD) age = 66.1 (7.1)). Linear regressions and ANOVA were used.Results: PwD reported slightly more negative ATOA than people without dementia; this relationship disappeared after controlling for depression and self-rated health. In PwD more positive ATOA showed negligible associations with better general cognition, memory performance, verbal fluency, and visuospatial ability. However, after adjusting for covariates only better visuospatial ability predicted more positive ATOA. Additional analyses showed that before and after controlling for covariates, individuals with poorer self-reported visual acuity have more negative ATOA. Amongst dementia subtypes, people with Parkinson’s disease dementia and dementia with Lewy bodies reported most negative ATOA. Conclusions: ATOA between PwD and people without dementia do not differ. ATOA in PwD appear to be affected not by cognitive impairment but by other characteristics that vary across dementia subtypes. Among PwD, those with Parkinson’s disease dementia and dementia with Lewy bodies may have higher risk of experiencing negative ATOA due to the motor and visual impairments that they experience.
Abstract.
Sabatini S, Ukoumunne O, Ballard C, Collins R, Anstey K, Diehl M, Brothers A, Wahl H-W, Corbett A, Hampshire A, et al (In Press). Cross-Sectional Association between Objective Cognitive Performance and Perceived Age-related Gains and Losses in Cognition. International Psychogeriatrics
Sabatini S, Ukoumunne O, Brothers A, Diehl M, Wahl H-W, Ballard C, Collins R, Corbett A, Brooker H, Clare L, et al (In Press). Differences in Awareness of Positive and Negative Age-Related Changes Account for Variability in Health Outcomes.
Abstract:
Differences in Awareness of Positive and Negative Age-Related Changes Account for Variability in Health Outcomes
Abstract
. Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health. We used cross-sectional data from the PROTECT study (N= 6,192; mean(SD) age= 66.1(7.0)). Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-square tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4. Experiencing one’s ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
Abstract.
Sabatini S, Ukoumunne O, Brothers A, Diehl M, Wahl H-W, Clive B, Collins R, Corbett A, Brooker H, Clare L, et al (In Press). Differences in awareness of positive and negative age-related changes account for variability in health outcomes.
European Journal of AgeingAbstract:
Differences in awareness of positive and negative age-related changes account for variability in health outcomes
Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health.
We used cross-sectional data from the PROTECT study (N= 6,192; mean (SD) age= 66.1(7.0)).
Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-squared tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4.
Experiencing one’s ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
Abstract.
Ballard C, Brooker H, Corbett A, Ismail Z, Creese B, Wesnes K (In Press). FLAME: a computerized neuropsychological composite for trials in early dementia. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Creese B, Brooker H, Aarsland D, Corbett A, Ballard C, Ismail Z (In Press). Genetic risk for Alzheimer disease, cognition and Mild Behavioral Impairment in healthy older adults.
Abstract:
Genetic risk for Alzheimer disease, cognition and Mild Behavioral Impairment in healthy older adults
BACKGROUND: Mild Behavioral Impairment (MBI) is a neuropsychiatric syndrome describing later-life emergent apathy, mood/anxiety symptoms, impulse dyscontrol, social inappropriateness and psychosis that are not attributable to psychiatric diagnoses. MBI is an at-risk state for incident cognitive decline and dementia, and is associated with dementia biomarkers including amyloid beta; and neurofilament light. Thus, MBI may be an early clinical marker of neurodegenerative disease. In this study, we hypothesized that stratification by MBI in a cognitively normal sample would moderate the signal between Alzheimer disease (AD) genetic risk and cognition.
METHODS: Genetic, cognitive and MBI data was available for 3,126 PROTECT study participants over 50 without dementia. A general cognitive composite score was constructed based on scores on paired associates learning, digit span, self-ordered search and verbal reasoning. MBI was assessed using the MBI Checklist. Polygenic scores for AD were split by tertile (representing low, medium and high risk) and the sample was stratified by MBI into those with no symptoms and those with any symptoms.
RESULTS: AD genetic risk was associated with poorer cognition in the MBI strata only (MBI: F(2,1746)=4.95, p=0.007; no MBI: F(2,1366)=0.72, p=0.49). The mean difference between low and high genetic risk groups was significant (p=0.005) and the standardised effect size in the MBI sample was higher than in the whole sample.
CONCLUSIONS: These findings justify MBI screening to enrich samples with at-risk individuals, and underscore the importance of late-life neuropsychiatric symptoms in cognitive ageing.
Abstract.
Creese B, Arathimos R, Brooker H, Aarsland D, Corbett A, Lewis C, Ballard C, Ismail Z (In Press). Genetic risk for Alzheimer’s disease, cognition and Mild Behavioral Impairment in healthy older adults. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Clare L, Kudlicka A, Oyebode JR, Jones RW, Bayer A, Leroi I, Kopelman M, James IA, Culverwell A, Pool J, et al (In Press). Goal-oriented cognitive Rehabilitation in Early-stage Alzheimer’s and related dementias: a multi-centre single-blind randomised controlled Trial (GREAT). Health Technology Assessment
Ballard C, Creese B, Gatt A, Doherty P, Francis PT, Whitfield D, Corbett A, Corcoran J, Hanger D, Thuret S, et al (In Press). Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease.
Abstract:
Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease
AbstractThe current paper describes the identification of novel candidate compounds for repositioning as treatments for Alzheimer’s disease (AD) from the CMAP library. Candidate compounds were identified based on inverse correlation with transcriptome signatures developed from meta-analyses of Alzheimer RNA expression studies using the SPIED platform. The 78 compounds with a significant inverse correlation were taken forward into an in vitro programme using 6 well validated screening assays relevant to potential treatment targets in AD. Nineteen pf the compounds were hits in at least 2 of these assays. A description of each of these compounds is presented.
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sabatini S, Ukoumunne OC, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (In Press). International relevance of Two Measures of Awareness of Age-Related Change (AARC).
Abstract:
International relevance of Two Measures of Awareness of Age-Related Change (AARC)
Abstract
. Background: a questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over. Methods: Data from 9,410 participants (Mean (SD) age= 65.9 (7.1)) in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across men and women, individuals with and without a university degree, and in middle age, early old age, and advanced old age; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We explored the relationship between demographic variables (age, sex, marital status, employment, and university education) and AARC. Results: We confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability and good convergent validity for AARC losses, but weak convergent validity for AARC gains. For both scales metric invariance was held for the two subgroups defined by education level and age. For the AARC-50 subscale, but not for the AARC-10 SF, strong invariance was also held for the two subgroups defined by sex. Age, sex, marital status, employment, and university education predicted AARC gains and losses. Conclusions: the AARC-10 SF and AARC-50 cognitive functioning subscale identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
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Arathimos R, Fabbri C, Vassos E, Davis KAS, Pain O, Gillett A, Coleman JRI, Hanscombe K, Hagenaars S, Jermy B, et al (In Press). Latent subtypes of manic or irritable episode symptoms in two population-based cohorts.
Abstract:
Latent subtypes of manic or irritable episode symptoms in two population-based cohorts
AbstractBackgroundEpisodic changes in mood characterise disorders such as bipolar disorder, which includes distinct periods of manic excitability or irritability, along with additional symptoms experienced during these periods. Common clinical understanding informs diagnostic criteria and epidemiological studies reflect clinical thresholds.AimsTo use a data-driven approach to defining groupings of symptoms experienced during periods of manic or irritable mood, which could inform understanding of mood disorders and guide case classification by identifying subgroups with homogeneous clinical/functional outcomes.MethodsWe used latent class analysis (LCA) to conduct an exploration of the latent structure in symptom responses in the UK Biobank and PROTECT studies, by investigating how symptoms, experienced during periods of manic or irritable mood, formed latent subgroups. We tested associations of latent subgroups with sociodemographic characteristics, diagnoses of psychiatric disorders and polygenic risk scores (PRS).ResultsFive latent classes were identified that captured patterns of symptoms experienced during periods of manic or irritable mood (N=42,183) in UK Biobank. We identified one class that experienced disruptive episodes of mostly irritable mood that was largely comprised of cases of depression/anxiety, and a class of individuals with increased confidence/creativity that reported lower disruptiveness and lower functional impairment. The five latent classes were replicated in an independent cohort, the PROTECT study (N=4,445), with similar distinctions between classes.ConclusionOur data-driven approach to grouping individuals identified distinct latent classes. A dimensional classification of mood disorders informed by our findings will be able to better assess or subtype these disorders in future studies.
Abstract.
Creese B, Khan Z, Henley W, O'Dwyer S, Corbett A, Vasconcelos Da Silva M, Mills K, Wright N, Testad I, Aarsland D, et al (In Press). Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety in adults over 50 between 2015 and 2020. International Psychogeriatrics
Creese BA, Brooker H, Ismail Z, Wesnes K, Adam H, Khan Z, Maria M, Corbett A, Aarsland D, Ballard C, et al (In Press). Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults. American Journal of Geriatric Psychiatry
Rao R, Creese B, Aarsland D, Kalafatis C, Khan Z, Corbett A, Ballard C (In Press). Risky drinking and cognitive impairment in community residents. aged 50 and over. Aging and Mental Health
Wolfova K, Creese B, Aarsland D, Ismail Z, Corbett A, Ballard C, Hampshire A, Cermakova P (In Press). Sex differences in the association of mild behavioral impairment with cognitive aging.
Abstract:
Sex differences in the association of mild behavioral impairment with cognitive aging
ABSTRACTINTRODUCTIONWe aimed to explore sex differences in the association of mild behavioral impairment (MBI) with the level of cognitive performance and its rate of decline in a cohort of people without dementia with the longest term follow up of cognition.METHODSWe studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models.RESULTSMales exhibited more often symptoms of decreased motivation, impulse dyscontrol and social inappropriateness, while less often symptoms of emotional dysregulation. The associations of MBI domains with some measures of cognitive performance and decline was stronger in males than females, with the exception of emotional dysregulation.DISCUSSIONMBI may influence cognition to a greater extent in males than in females.
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Allan L, Corbett A, Valderas Martinez J (In Press). Social prescribing programmes to prevent or delay frailty in community-dwelling older adults. Geriatrics
Sabatini S, Ukoumunne O, Ballard C, Collins R, Corbett A, Brooker H, Clare L (In Press). The Cross-sectional Relationship between Pain and Awareness of Age-Related Changes. British Journal of Pain
Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, et al (In Press). The Dementias Platform UK (DPUK) Data Portal.
Abstract:
The Dementias Platform UK (DPUK) Data Portal
AbstractThe Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data.The Data Portal uses UK Secure eResearch Platform (UKSeRP) infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication.Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Project are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
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Stewart G, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Brooker H, Charlton R, Happe F (In Press). The cognitive profile of middle-aged and older adults with high vs. low autistic traits. Autism Research
Creese B, Corbett A, Ballard C (In Press). The mental and physical health of older adults with a genetic predisposition for autism. Autism Research: official journal of the International Society for Autism Research
sabatini S, Ukoumunne O, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (In Press). UK Validation of Two Measures of Awareness of Age-Related Change (AARC).
Abstract:
UK Validation of Two Measures of Awareness of Age-Related Change (AARC)
Abstract
. Background: a questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over. Methods: Data from 14,797 participants in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across males and females and across individuals with and without a university degree; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We also explored the relationship between demographic variables and AARC. Results: We confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability and convergent validity. The meaning of AARC gains and losses was the same across males and females and across individuals with and without a university degree. Items composing AARC scales had the same meaning across individuals with and without a university degree. Items composing the AARC-50 cognitive functioning subscale had the same meaning across males and females. Two items in the AARC-10 SF had different meaning across males and females. Demographic variables significantly predicted AARC gains and losses. Conclusions: the AARC-10 SF and AARC-50 cognitive functioning subscale can help to identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
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O'Nions E, Petersen I, Buckman JEJ, Charlton R, Cooper C, Corbett A, Happé F, Manthorpe J, Richards M, Saunders R, et al (2023). Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data. The Lancet Regional Health - Europe, 29, 100626-100626.
McDermid J, Ballard C, Khan Z, Aarsland D, Fox C, Fossey J, Clare L, Moniz-Cook E, Soto-Martin M, Sweetnam A, et al (2023). Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.
Int J Geriatr Psychiatry,
38(1).
Abstract:
Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.
OBJECTIVES: This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS: This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS: Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p
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Sabatini S, Dritschel B, Rupprecht FS, Ukoumunne OC, Ballard C, Brooker H, Corbett A, Clare L (2023). Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.
Aging Ment Health, 1-9.
Abstract:
Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.
OBJECTIVE: Lower awareness of age-related gains (AARC-gains) and higher awareness of age-related losses (AARC-losses) may be risk factors for depressive and anxiety symptoms. We explored whether: (1) Baseline AARC-gains and AARC-losses predict depressive and anxiety symptoms at one-year follow-up; (2) age and rumination moderate these associations; (3) levels of AARC-gains and AARC-losses differ among individuals with different combinations of current and past depression and/or with different combinations of current and past anxiety. METHODS: in this one-year longitudinal cohort study participants (N = 3386; mean age = 66.0; SD = 6.93) completed measures of AARC-gains, AARC-losses, rumination, depression, anxiety, and lifetime diagnosis of depression and anxiety in 2019 and 2020. Regression models with tests of interaction were used. RESULTS: Higher AARC-losses, but not lower AARC-gains, predicted more depressive and anxiety symptoms. Age did not moderate these associations. Associations of lower AARC-gains and higher AARC-losses with more depressive symptoms and of higher AARC-losses with more anxiety symptoms were stronger in those with higher rumination. Individuals with both current and past depression reported highest AARC-losses and lowest AARC-gains. Those with current, but not past anxiety, reported highest AARC-losses. CONCLUSION: Perceiving many age-related losses may place individuals at risk of depressive and anxiety symptoms, especially those who frequently ruminate.
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Sabatini S, Ukoumunne OC, Brothers A, Diehl M, Wahl H-W, Ballard C, Collins R, Corbett A, Brooker H, Clare L, et al (2022). Differences in awareness of positive and negative age-related changes accounting for variability in health outcomes.
Eur J Ageing,
19(4), 1087-1097.
Abstract:
Differences in awareness of positive and negative age-related changes accounting for variability in health outcomes.
Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health. We used cross-sectional data from the PROTECT study (N = 6192; mean (SD) age = 66.1 (7.0)). Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-squared tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4. Experiencing one's ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
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Sabatini S, Ukoumunne OC, Ballard C, Collins R, Corbett A, Brooker H, Clare L (2022). Exploring awareness of age-related changes among over 50s in the UK: findings from the PROTECT study.
Int Psychogeriatr,
34(9), 789-803.
Abstract:
Exploring awareness of age-related changes among over 50s in the UK: findings from the PROTECT study.
OBJECTIVES: Older people describe positive and negative age-related changes, but we do not know much about what contributes to make them aware of these changes. We used content analysis to categorize participants' written comments and explored the extent to which the identified categories mapped onto theoretical conceptualizations of influences on awareness of age-related change (AARC). DESIGN: Cross-sectional observational study. PARTICIPANTS: the study sample comprised 609 UK individuals aged 50 years or over (mean (SD) age = 67.9 (7.6) years), enrolled in the PROTECT study. MEASUREMENTS: Between January and March 2019, participants provided demographic information, completed a questionnaire assessing awareness of age-related change (AARC-10 SF), and responded to an open-ended question asking them to comment on their responses. RESULTS: While some of the emerging categories were in line with the existing conceptual framework of AARC (e.g. experiencing negative changes and attitudes toward aging), others were novel (e.g. engagement in purposeful activities or in activities that distract from age-related thoughts). Analysis revealed some of the thought processes involved in selecting responses to the questionnaire items, demonstrating different ways in which people make sense of specific items. CONCLUSIONS: Results support the ability of the AARC questionnaire to capture perceived age-related changes in cognitive functioning, physical and mental health, and engagement in social activities and in healthy and adaptive behaviors. However, findings also suggest ways of enriching the theoretical conceptualization of how AARC develops and offer insights into interpretation of responses to measures of AARC.
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Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2022). Traumatic life experiences and post‐traumatic stress symptoms in middle‐aged and older adults with and without autistic traits. International Journal of Geriatric Psychiatry, 37(2).
Wilson KE, Corbett A, Van Horn A, Guevara Beltran D, Ayers JD, Alcock J, Aktipis A (2021). Associations Between Change over Time in Pandemic-Related Stress and Change in Physical Activity.
J Phys Act Health,
18(11), 1419-1426.
Abstract:
Associations Between Change over Time in Pandemic-Related Stress and Change in Physical Activity.
BACKGROUND: Physical activity (PA) mitigated psychological distress during the initial weeks of the COVID-19 pandemic, yet not much is known about whether PA had effects on stress in subsequent months. We examined the relationship between change over time in COVID-related stress and self-reported change in PA between March and July 2020. METHODS: Latent growth modeling was used to examine trajectories of change in pandemic-related stress and test their association with self-reported changes in PA in an international sample (n = 679). RESULTS: the participants reported a reduction in pandemic-related stress between April and July of 2020. Significant linear (factor mean = -0.22) and quadratic (factor mean = 0.02) changes (Ps <. 001) were observed, indicating a deceleration in stress reduction over time. Linear change was related to change in PA such that individuals who became less active during the pandemic reported less stress reduction over time compared with those who maintained or increased their PA during the pandemic. CONCLUSIONS: Individuals who experienced the greatest reduction in stress over time during the pandemic were those who maintained their activity levels or became more active. Our study cannot establish a causal relationship between these variables, but the findings are consistent with other work showing that PA reduces stress.
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Sabatini S, Ukoumunne O, Ballard C, Collins R, Corbett A, Brooker H, Clare L (2021). Cross-sectional and longitudinal associations between subjective sleep difficulties and self-perceptions of aging. Behavioral Sleep Medicine
Ritchie S, Lawrence V, Jones J, Corbett A (2021). Engaging older adults in an online physical activity programme to improve cognition: a qualitative study. International Journal of Geriatric Psychiatry, 36(12), 1942-1949.
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2021). Predictors of activities of daily living in heathy older adults: Who benefits most from online cognitive training?.
Brain Behav,
11(11).
Abstract:
Predictors of activities of daily living in heathy older adults: Who benefits most from online cognitive training?
OBJECTIVES: to investigate the course of activities of daily living (IADL) functioning and possible predictors of performance changes in healthy older adults conducting either a General Cognitive Training (GCT) or a Reasoning Cognitive Training (ReaCT) or no training (control group, CG) over a period of 6 weeks, 3 months, and 6 months. SETTING AND PARTICIPANTS: an online, home-based GCT and ReaCT including n = 2913 healthy participants (GCT: n = 1096; ReaCT: n = 1022; CG: n = 794) aged 60 years and older. METHODS: Multilevel analysis were calculated to explore the nature of our outcome variables of IADL part a (independence) and part B (difficulty of tasks), and to detect possible predictors for participants' performance on IADL after CT. RESULTS: the random slopes models fitted better for the outcomes IADL Part B in the GCT group (χ2 (2) = 18.78, p
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Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2021). The Mental and Physical Health Profiles of Older Adults Who Endorse Elevated Autistic Traits.
J Gerontol B Psychol Sci Soc Sci,
76(9), 1726-1737.
Abstract:
The Mental and Physical Health Profiles of Older Adults Who Endorse Elevated Autistic Traits.
OBJECTIVES: the mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits and in older age. METHODS: a total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent sociocommunicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the "Autism Spectrum Trait" (AST) group. An age- and gender-matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the "Control Older Adults" (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. RESULTS: the AST group reported significantly elevated rates of psychiatric diagnoses compared to the COA group. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than the COA group. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. DISCUSSION: These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between the propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care.
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Sabatini S, Ukoumunne OC, Ballard C, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, Brooker H, Clare L, et al (2021). What does feeling younger or older than one’s chronological age mean to men and women? Qualitative and quantitative findings from the PROTECT study. Psychology & Health, 38(3), 324-347.
Ballard C, Corbett A, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Wiliams G, Doherty P, et al (2020). Drug repositioning and repurposing. for Alzheimer disease. Nature Reviews Neurology
Ballard C, Orrell M, Moniz-Cook E, Woods R, Whitaker R, Corbett A, Aarsland D, Murray J, Lawrence V, Testad I, et al (2020). Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs.
Programme Grants for Applied Research,
8(6), 1-98.
Abstract:
Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs
. Background
. The effective management of agitation and other neuropsychiatric and behavioural symptoms in people with dementia is a major challenge, particularly in care home settings, where dementia severity is higher and there is limited training and support for care staff. There is evidence for the value of staff training and the use of psychosocial approaches; however, no intervention currently exists that combines these elements into an intervention that is fit for purpose and effective in these settings based on evidence from a randomised controlled trial.
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. Objective
. The objective was to develop and evaluate a complex intervention to improve well-being, reduce antipsychotic use and improve quality of life in people with dementia in care homes through person-centred care, management of agitation and non-drug approaches.
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. Design
. This was a 5-year programme that consisted of six work packages. Work package 1 consisted of two systematic reviews of personalised psychosocial interventions for behavioural and psychological symptoms for people with dementia in care homes. Work package 2 consisted of a metasynthesis of studies examining implementation of psychosocial interventions, in addition to developing a draft Well-being and Health for people with Dementia (WHELD) programme. Work package 3 consisted of a factorial study of elements of the draft WHELD programme in 16 care homes. Work package 4 involved optimisation of the WHELD programme based on work package 3 data. Work package 5 involved a multicentre randomised controlled trial in 69 care homes, which evaluated the impact of the optimised WHELD programme on quality of life, agitation and overall neuropsychiatric symptoms in people with dementia. Work package 6 focused on dissemination of the programme.
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. Setting
. This programme was carried out in care homes in the UK.
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. Participants
. Participants of this programme were people with dementia living in care homes, and the health and care professionals providing treatment and care in these settings.
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. Results
. Work package 1: reviews identified randomised controlled trials and qualitative evidence supporting the use of psychosocial approaches to manage behavioural symptoms, but highlighted a concerning lack of evidence-based training manuals in current use. Work package 2: the meta-analysis identified key issues in promoting the use of interventions in care homes. The WHELD programme was developed through adaptation of published approaches. Work package 3: the factorial trial showed that antipsychotic review alone significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval 0.05 to 0.60). Antipsychotic review plus social interaction significantly reduced mortality (odds ratio 0.36, 95% confidence interval 0.23 to 0.57), but this group showed significantly worse outcomes in behavioural and psychological symptoms of dementia than the group receiving neither antipsychotic review nor social interaction (mean difference 7.37 symptoms, 95% confidence interval 1.53 to 13.22 symptoms). This detrimental impact was reduced when combined with social interaction (mean difference –0.44 points, 95% confidence interval –4.39 to 3.52 points), but with no significant benefits for agitation. The exercise intervention significantly improved neuropsychiatric symptoms (mean difference –3.58 symptoms, 95% confidence interval –7.08 to –0.09 symptoms) but not depression (mean difference –1.21 points, 95% confidence interval –4.35 to 1.93 points). Qualitative work with care staff provided additional insights into the acceptability and feasibility of the intervention. Work package 4: optimisation of the WHELD programme led to a final version that combined person-centred care training with social interaction and pleasant activities. The intervention was adapted for delivery through a ‘champion’ model. Work package 5: a large-scale, multicentre randomised controlled trial in 69 care homes showed significant benefit to quality of life, agitation and overall neuropsychiatric symptoms, at reduced overall cost compared with treatment as usual. The intervention conferred a statistically significant improvement in quality of life (Dementia Quality of Life Scale – Proxy z-score of 2.82, mean difference 2.54, standard error of measurement 0.88, 95% confidence interval 0.81 to 4.28, Cohen’s d effect size of 0.24; p = 0.0042). There were also statistically significant benefits in agitation (Cohen-Mansfield Agitation Inventory z-score of 2.68, mean difference –4.27, standard error of measurement 1.59, 95% confidence interval –7.39 to –1.15, Cohen’s d effect size of 0.23; p = 0.0076) and overall neuropsychiatric symptoms (Neuropsychiatric Inventory – Nursing Home version z-score of 3.52, mean difference –4.55, standard error of measurement 1.28, 95% confidence interval –7.07 to –2.02, Cohen’s d of 0.30; p < 0.001). The WHELD programme contributed to significantly lower health and social care costs than treatment as usual (cost difference –£4740, 95% confidence interval –£6129 to –£3156). Focus groups were conducted with 47 staff up to 12 months after the end of work package 5, which demonstrated sustained benefits. Work package 6: the outputs of the programme were translated into general practitioner workshops and a British Medical Journal e-learning module, an updated national best practice guideline and a portfolio of lay and care home outreach activities.
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. Limitations
. Residents with dementia were not involved in the qualitative work.
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. Conclusions
. The WHELD programme is effective in improving quality of life and reducing both agitation and overall neuropsychiatric symptoms in people with dementia in care homes. It provides a structured training and support intervention for care staff, with lower overall costs for resident care than treatment as usual.
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. Future work
. It will be important to consider the long-term sustainability of the WHELD programme and cost-effective means of long-term implementation.
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. Trial registration
. Current Controlled Trials ISRCTN40313497 and ISRCTN62237498.
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. Funding
. This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 6. See the NIHR Journals Library website for further project information.
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Abstract.
Sabatini S, Ukoumunne O, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (2020). International relevance of Two Measures of Awareness of Age-Related Change (AARC). BMC Geriatrics, 20
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2020). Lower cognitive baseline scores predict cognitive training success after 6 months in healthy older adults: Results of an online. <scp>RCT</scp>. International Journal of Geriatric Psychiatry, 35(9), 1000-1008.
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2020). Predictors of changes after reasoning training in healthy adults. Brain and Behavior, 10(12).
Ballard C, Corbett A (2020). Reducing psychotropic drug use in people with dementia living in nursing homes. International Psychogeriatrics, 32(3), 291-294.
Creese B, Brooker H, Aarsland D, Corbett A, Ballard C, Ismail Z (2020). Relationship between genetic risk for Alzheimer's, cognition and neuropsychiatric symptoms: a case study of DNA sampling and analysis through digital platform cohort studies. Alzheimer's & Dementia, 16(S10).
Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2020). Sleep problems and mental health difficulties in older adults who endorse high autistic traits.
Research in Autism Spectrum Disorders,
77Abstract:
Sleep problems and mental health difficulties in older adults who endorse high autistic traits
Background: Sleep problems and mental health difficulties are common in autistic children and young adults. However, these problems have seldom been studied in older autistic adults, or in older adults with elevated autistic traits. Method: Cross-sectional data was examined from 13,897 adults aged 50–81 years taking part in the PROTECT study, who reported whether they experienced persistent socio-communicative autistic traits. Approximately 1%, 187 individuals, were identified as endorsing high autistic traits in childhood and currently, henceforth ‘Autism Spectrum Trait’ (AST) group. An age- and gender-matched comparison group was formed of 6740 individuals who endorsed no autistic traits, henceforth ‘Control Older Adults’ (COA) group. Differences between AST and COA groups were explored in self-reported sleep behaviors, and in depression and anxiety symptoms. Results: AST and COA groups reported similar sleep duration and depth, and nighttime waking frequency. However, the AST group reported significantly more problems with falling asleep, morning drowsiness, and lower sleep quality/satisfaction than COA. More AST adults reported sleep problems past cut-off, as well as clinical levels of depression and anxiety, compared to COA. Adults in both groups who met criteria for high sleep problems experienced more mental health difficulties than those with few sleep problems. However, even amongst those without depression/anxiety, the AST group reported more sleep problems than the COA. Conclusions: These associations suggest that older adults with high autistic traits, like diagnosed autistic children/young adults, may experience poorer sleep and more mental health difficulties than those with low autistic traits. Further work is needed to see whether these results extend to older individuals meeting diagnostic criteria for autism.
Abstract.
Robinson L, Poole M, McLellan E, Lee R, Amador S, Bhattarai N, Bryant A, Coe D, Corbett A, Exley C, et al (2020). Supporting good quality, community-based end-of-life care for people living with dementia: the SEED research programme including feasibility RCT.
Programme Grants for Applied Research,
8(8), 1-254.
Abstract:
Supporting good quality, community-based end-of-life care for people living with dementia: the SEED research programme including feasibility RCT
BackgroundIn the UK, most people with dementia die in the community and they often receive poorer end-of-life care than people with cancer.ObjectiveThe overall aim of this programme was to support professionals to deliver good-quality, community-based care towards, and at, the end of life for people living with dementia and their families.DesignThe Supporting Excellence in End-of-life care in Dementia (SEED) programme comprised six interlinked workstreams. Workstream 1 examined existing guidance and outcome measures using systematic reviews, identified good practice through a national e-survey and explored outcomes of end-of-life care valued by people with dementia and family carers (n = 57) using a Q-sort study. Workstream 2 explored good-quality end-of-life care in dementia from the perspectives of a range of stakeholders using qualitative methods (119 interviews, 12 focus groups and 256 observation hours). Using data from workstreams 1 and 2, workstream 3 used co-design methods with key stakeholders to develop the SEED intervention. Worksteam 4 was a pilot study of the SEED intervention with an embedded process evaluation. Using a cluster design, we assessed the feasibility and acceptability of recruitment and retention, outcome measures and our intervention. Four general practices were recruited in North East England: two were allocated to the intervention and two provided usual care. Patient recruitment was via general practitioner dementia registers. Outcome data were collected at baseline, 4, 8 and 12 months. Workstream 5 involved economic modelling studies that assessed the potential value of the SEED intervention using a contingent valuation survey of the general public (n = 1002). These data informed an economic decision model to explore how the SEED intervention might influence care. Results of the model were presented in terms of the costs and consequences (e.g. hospitalisations) and, using the contingent valuation data, a cost–benefit analysis. Workstream 6 examined commissioning of end-of-life care in dementia through a narrative review of policy and practice literature, combined with indepth interviews with a national sample of service commissioners (n = 20).SettingThe workstream 1 survey and workstream 2 included services throughout England. The workstream 1 Q-sort study and workstream 4 pilot trial took place in North East England. For workstream 4, four general practices were recruited; two received the intervention and two provided usual care.ResultsCurrently, dementia care and end-of-life care are commissioned separately, with commissioners receiving little formal guidance and training. Examples of good practice rely on non-recurrent funding and leadership from an interested clinician. Seven key components are required for good end-of-life care in dementia: timely planning discussions, recognising end of life and providing supportive care, co-ordinating care, effective working with primary care, managing hospitalisation, continuing care after death, and valuing staff and ongoing learning. Using co-design methods and the theory of change, the seven components were operationalised as a primary care-based, dementia nurse specialist intervention, with a care resource kit to help the dementia nurse specialist improve the knowledge of family and professional carers. The SEED intervention proved feasible and acceptable to all stakeholders, and being located in the general practice was considered beneficial. None of the outcome measures was suitable as the primary outcome for a future trial. The contingent valuation showed that the SEED intervention was valued, with a wider package of care valued more than selected features in isolation. The SEED intervention is unlikely to reduce costs, but this may be offset by the value placed on the SEED intervention by the general public.LimitationsThe biggest challenge to the successful delivery and completion of this research programme was translating the ‘theoretical’ complex intervention into practice in an ever-changing policy and service landscape at national and local levels. A major limitation for a future trial is the lack of a valid and relevant primary outcome measure to evaluate the effectiveness of a complex intervention that influences outcomes for both individuals and systems.ConclusionsAlthough the dementia nurse specialist intervention was acceptable, feasible and integrated well with existing care, it is unlikely to reduce costs of care; however, it was highly valued by all stakeholders (professionals, people with dementia and their families) and has the potential to influence outcomes at both an individual and a systems level.Future workThere is no plan to progress to a full randomised controlled trial of the SEED intervention in its current form. In view of new National Institute for Health and Care Excellence dementia guidance, which now recommends a care co-ordinator for all people with dementia, the feasibility of providing the SEED intervention throughout the illness trajectory should be explored. Appropriate outcome measures to evaluate the effectiveness of such a complex intervention are needed urgently.Trial registrationCurrent Controlled Trials ISRCTN21390601.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 8, No. 8. See the NIHR Journals Library website for further project information.
Abstract.
Desai R, Charlesworth GM, Brooker HJ, Potts HWW, Corbett A, Aarsland D, Ballard CG (2020). Temporal Relationship Between Depressive Symptoms and Cognition in Mid and Late Life: a Longitudinal Cohort Study.
Journal of the American Medical Directors Association,
21(8), 1108-1113.
Abstract:
Temporal Relationship Between Depressive Symptoms and Cognition in Mid and Late Life: a Longitudinal Cohort Study
Objectives: to examine the bidirectional temporal relationship between depressive symptoms and cognition in relation to risk, reaction, and prodrome. Design: Cross-lag analysis of longitudinal data collected online at baseline and 12-month follow-up. Setting and Participants: a United Kingdom population cohort of 11,855 participants aged 50 years and over. Measures: Patient Health Questionnaire-9 (depressive symptoms), cognitive measures: Paired Associate Learning, Verbal Reasoning, Spatial Working Memory, and Digit Span. Results: Depressive symptoms predicted a decline in paired associates learning [β = −.020, P =. 013, (95% confidence interval [CI], ‒.036, −.004)] and verbal reasoning [β = −.014, P =. 016, (95% CI ‒.025, −.003)] but not vice versa. Depressive symptoms predicted [β = −.043, P <. 001, (95% CI ‒.060, −.026); β = −.029, P <. 001, (95% CI ‒.043, −.015)] and were predicted by [β = −.030, P = <. 001, (95% CI ‒.047, −.014); β = −.025, P =. 003, (95% CI ‒.041, −.009)], a decline in spatial working memory and verbal digit span, respectively. Conclusions and Implications: Depressive symptoms may be either a risk factor or prodrome for cognitive decline. In addition, a decline in attention predicts depressive symptoms. Clinical implications and implications for further research are discussed.
Abstract.
Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, et al (2020). The Dementias Platform UK (DPUK) Data Portal.
Eur J Epidemiol,
35(6), 601-611.
Abstract:
The Dementias Platform UK (DPUK) Data Portal.
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Abstract.
Author URL.
Brooker H, Wesnes KA, Ballard C, Hampshire A, Aarsland D, Khan Z, Stenton R, McCambridge L, Corbett A (2019). An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults.
Int J Geriatr Psychiatry,
34(7), 921-931.
Abstract:
An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults.
OBJECTIVE: the identification of modifiable lifestyle factors to preserve cognitive function in older individuals becomes increasingly of importance. This study examines whether word puzzle use is related to cognitive function in older adults. METHODS: Cognitive data from 19 078 cognitively healthy individuals aged 50 to 93 years enrolled into the online PROTECT study were evaluated for self-reported frequency of performing word puzzles on a six-point scale, ranging from "more than once per day" to "never". Nine cognitive tests covered a range of domains including focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analyses of covariance were used to determine any differences between the six response groups. RESULTS: Each of the 14 cognitive measures analysed showed highly statistically significant main effects of the frequency of performing word puzzles. For each measure, the group who never performed word puzzles performed most poorly, with the group who reported occasional puzzle use also performing more poorly than virtually every other group. Measures of speed provided the greatest discriminations, with a grammatical reasoning score differentiating the two highest frequency groups, performing word puzzles daily or more than once daily. CONCLUSIONS: the frequency of word puzzle use is directly related to cognitive function in adults aged 50 and over. Future work needs to determine whether engaging in such puzzles can favourably influence cognitive trajectory with age.
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Author URL.
Ballard C, Corbett A (2019). Commentary: Opportunities for Combination Trials.
J Prev Alzheimers Dis,
6(3), 177-178.
Author URL.
Newman L, Stoner C, Corbett A, Megalogeni M, Khan Z, Spector A (2019). Development of the ‘SNS older adults measure’ (SNS-OA) to examine social network site use in older adults. Aging & Mental Health, 25(1), 68-77.
Eraydin IE, Mueller C, Corbett A, Ballard C, Brooker H, Wesnes K, Aarsland D, Huntley J (2019). Investigating the relationship between age of onset of depressive disorder and cognitive function.
Int J Geriatr Psychiatry,
34(1), 38-46.
Abstract:
Investigating the relationship between age of onset of depressive disorder and cognitive function.
OBJECTIVES: Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance. METHODS: This study examined baseline cross-sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early-onset, midlife-onset, and late-onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models. RESULTS: the late-onset depression group scored significantly lower on the verbal reasoning task than the early-onset group while there were no significant differences found on the other tasks. Midlife-onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early-onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks. CONCLUSIONS: the most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late-onset depression may be associated with more executive impairment than an early-onset depression.
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Author URL.
Testad I, Kajander M, Froiland CT, Corbett A, Gjestsen MT, Anderson JG (2019). Nutritional Interventions for Persons with Early-Stage Dementia or Alzheimer's Disease: an Integrative Review.
Res Gerontol Nurs,
12(5), 259-268.
Abstract:
Nutritional Interventions for Persons with Early-Stage Dementia or Alzheimer's Disease: an Integrative Review.
Persons with Alzheimer's disease and related dementias (ADRD) are at particular risk of malnutrition and weight loss. Clinical research concerning the role and impact of nutritional intervention in early-stage ADRD, specifically on cognition and key symptoms such as behavior, is less straightforward. Thus, an integrative review was conducted to examine the literature pertaining to nutritional interventions for persons with ADRD and to make recommendations for priority areas for future research and practice. Findings from the studies reviewed highlight multiple potential opportunities for improving nutritional status and support for persons with ADRD living in the community. Despite the small amount of evidence, the six studies identified in the current review suggest a broad benefit may be conferred through educational approaches and nutritional supplementation. [Res Gerontol Nurs. 2019; 12(5):259-268.].
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Creese BA, Griffiths A, Brooker H, Corbett A, Aarsland D, Ballard C, Ismail Z (2019). Profile of Mild Behavioral Impairment and Factor Structure of the Mild Behavioral Impairment Checklist in Cognitively Normal Older Adults. International Psychogeriatrics
Creese B, Griffiths A, Brooker H, Corbett A, Aarsland D, Ballard C, Ismail Z (2019). Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults.
International Psychogeriatrics,
32(6), 705-717.
Abstract:
Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults
ABSTRACTObjectives:In this large population study, we set out to examine the profile of mild behavioral impairment (MBI) by using the Mild Behavioral Impairment Checklist (MBI-C) and to explore its factor structure when employed as a self-reported and informant-rated tool.Design:This was a population-based cohort study.Setting:Participants were recruited from the Platform for Research Online to Investigate Genetics and Cognition in Aging study (https://www.protect-exeter.org.uk).Participants:A total of 5,742 participant-informant dyads participated in the study.Measurements:Both participants and informants completed the MBI-C. The factor structure of the MBI-C was evaluated by exploratory factor analysis.Results:The most common MBI-C items, as rated by self-reported and informants, related to affective dysregulation (mood/anxiety symptoms), being present in 34% and 38% of the sample, respectively. The least common items were those relating to abnormal thoughts and perception (psychotic symptoms) (present in 3% and 6% of the sample, respectively). Only weak correlations were observed between self-reported and informant-reported MBI-C responses. Exploratory factor analysis for both sets of respondent answers indicated that a five-factor solution for the MBI-C was appropriate, reflecting the hypothesized structure of the MBI-C.Conclusion:This is the largest and most detailed report on the frequency of MBI symptoms in a nondementia sample. The full spectrum of MBI symptoms was present in our sample, whether rated by self-reported or informant report. However, we show that the MBI-C performs differently in self-reported versus informant-reported situations, which may have important implications for the use of the questionnaire in clinic and research.
Abstract.
Brooker H, Wesnes KA, Ballard C, Hampshire A, Aarsland D, Khan Z, Stenton R, Megalogeni M, Corbett A (2019). The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over.
Int J Geriatr Psychiatry,
34(7), 932-940.
Abstract:
The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over.
OBJECTIVE: Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number-puzzle use is related to cognitive function in older adults. METHODS: Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self-reported frequency of performing number puzzles. Two cognitive-test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups. RESULTS: Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant. CONCLUSIONS: This study has identified a close relationship between frequency of number-puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.
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Author URL.
Lane CA, Hardy J, Schott JM (2018). Alzheimer's disease.
EUROPEAN JOURNAL OF NEUROLOGY,
25(1), 59-70.
Author URL.
Nunez KM, Khan Z, Testad I, Lawrence V, Creese B, Corbett A (2018). Current practice and challenges in night-time care for people with dementia living in care homes: a qualitative study.
Int J Geriatr Psychiatry,
33(1), e140-e149.
Abstract:
Current practice and challenges in night-time care for people with dementia living in care homes: a qualitative study.
OBJECTIVE: to explore the current practices and challenges in night-time care for people with dementia living in care homes in the UK. METHODS: Focus group discussions (FGD) were held with care staff and family carers from five care homes in South London. To supplement the FGD data, an online survey was circulated to family carers (n = 16), and informal interviews were conducted with night-time care staff and nurses (n = 19). The questions for the online survey were designed to specifically explore the themes that emerged from the FGD. RESULTS: Thematic analysis revealed eight key themes in the management of sleep disturbance in people with dementia living in care homes: current night-time care practices, dissonance in perceived causes of sleep disturbances, inconsistencies in treatment options, insufficient staffing levels, working relationships between shifts, nurse burden and responsibility, communication as a critical challenge, connecting with residents and one overarching theme of balance. CONCLUSIONS: the findings of this study highlight the need for an evidence-based sleep disturbance management programme designed for use in care homes and informed by stakeholders. The key themes identified represent the major barriers to good quality care and areas which future programmes will need to address to improve the quality of night-time care in care homes. There are clearly opportunities for future examination of non-pharmacological night-time care management programmes for use in the population. Copyright © 2017 John Wiley & Sons, Ltd.
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Petyaeva A, Kajander M, Lawrence V, Clifton L, Thomas AJ, Ballard C, Leroi I, Briggs M, Closs J, Dening T, et al (2018). Feasibility of a staff training and support programme to improve pain assessment and management in people with dementia living in care homes.
Int J Geriatr Psychiatry,
33(1), 221-231.
Abstract:
Feasibility of a staff training and support programme to improve pain assessment and management in people with dementia living in care homes.
OBJECTIVES: the objective of this study was to establish the feasibility and initial effectiveness of training and support intervention for care staff to improve pain management in people with dementia living in care homes (PAIN-Dem). METHODS: PAIN-Dem training was delivered to care staff from three care homes in South London, followed by intervention support and resources to encourage improved pain management by staff over 4 weeks. Feasibility was assessed through fidelity to intervention materials and qualitative approaches. Focus group discussions with staff explored the use of the PAIN-Dem intervention, and interviews were held with six residents and family carers. Pain was assessed in all residents at baseline, 3 and 4 weeks, and goal attainment scaling was assessed at 4 weeks. RESULTS: Delivery of training was a key driver for success and feasibility of the PAIN-Dem intervention. Improvements in pain management behaviour and staff confidence were seen in homes where training was delivered in a care home setting across the care team with good manager buy-in. Family involvement in pain management was highlighted as an area for improvement. Goal attainment in residents was significantly improved across the cohort, although no significant change in pain was seen. CONCLUSIONS: This study shows good initial feasibility of the PAIN-Dem intervention and provides valuable insight into training and support paradigms that deliver successful learning and behaviour change. There is a need for a larger trial of PAIN-Dem to establish its impact on resident pain and quantifiable staff behaviour measures. Copyright © 2017 John Wiley & Sons, Ltd.
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Author URL.
Ballard C, Corbett A, Orrell M, Williams G, Moniz-Cook E, Romeo R, Woods B, Garrod L, Testad I, Woodward-Carlton B, et al (2018). Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial.
PLoS Med,
15(2).
Abstract:
Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial.
BACKGROUND: Agitation is a common, challenging symptom affecting large numbers of people with dementia and impacting on quality of life (QoL). There is an urgent need for evidence-based, cost-effective psychosocial interventions to improve these outcomes, particularly in the absence of safe, effective pharmacological therapies. This study aimed to evaluate the efficacy of a person-centred care and psychosocial intervention incorporating an antipsychotic review, WHELD, on QoL, agitation, and antipsychotic use in people with dementia living in nursing homes, and to determine its cost. METHODS AND FINDINGS: This was a randomised controlled cluster trial conducted between 1 January 2013 and 30 September 2015 that compared the WHELD intervention with treatment as usual (TAU) in people with dementia living in 69 UK nursing homes, using an intention to treat analysis. All nursing homes allocated to the intervention received staff training in person-centred care and social interaction and education regarding antipsychotic medications (antipsychotic review), followed by ongoing delivery through a care staff champion model. The primary outcome measure was QoL (DEMQOL-Proxy). Secondary outcomes were agitation (Cohen-Mansfield Agitation Inventory [CMAI]), neuropsychiatric symptoms (Neuropsychiatric Inventory-Nursing Home Version [NPI-NH]), antipsychotic use, global deterioration (Clinical Dementia Rating), mood (Cornell Scale for Depression in Dementia), unmet needs (Camberwell Assessment of Need for the Elderly), mortality, quality of interactions (Quality of Interactions Scale [QUIS]), pain (Abbey Pain Scale), and cost. Costs were calculated using cost function figures compared with usual costs. In all, 847 people were randomised to WHELD or TAU, of whom 553 completed the 9-month randomised controlled trial. The intervention conferred a statistically significant improvement in QoL (DEMQOL-Proxy Z score 2.82, p = 0.0042; mean difference 2.54, SEM 0.88; 95% CI 0.81, 4.28; Cohen's D effect size 0.24). There were also statistically significant benefits in agitation (CMAI Z score 2.68, p = 0.0076; mean difference 4.27, SEM 1.59; 95% CI -7.39, -1.15; Cohen's D 0.23) and overall neuropsychiatric symptoms (NPI-NH Z score 3.52, p < 0.001; mean difference 4.55, SEM 1.28; 95% CI -7.07,-2.02; Cohen's D 0.30). Benefits were greatest in people with moderately severe dementia. There was a statistically significant benefit in positive care interactions as measured by QUIS (19.7% increase, SEM 8.94; 95% CI 2.12, 37.16, p = 0.03; Cohen's D 0.55). There were no statistically significant differences between WHELD and TAU for the other outcomes. A sensitivity analysis using a pre-specified imputation model confirmed statistically significant benefits in DEMQOL-Proxy, CMAI, and NPI-NH outcomes with the WHELD intervention. Antipsychotic drug use was at a low stable level in both treatment groups, and the intervention did not reduce use. The WHELD intervention reduced cost compared to TAU, and the benefits achieved were therefore associated with a cost saving. The main limitation was that antipsychotic review was based on augmenting processes within care homes to trigger medical review and did not in this study involve proactive primary care education. An additional limitation was the inherent challenge of assessing QoL in this patient group. CONCLUSIONS: These findings suggest that the WHELD intervention confers benefits in terms of QoL, agitation, and neuropsychiatric symptoms, albeit with relatively small effect sizes, as well as cost saving in a model that can readily be implemented in nursing homes. Future work should consider how to facilitate sustainability of the intervention in this setting. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62237498.
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Huntley J, Corbett A, Wesnes K, Brooker H, Stenton R, Hampshire A, Ballard C (2018). Online assessment of risk factors for dementia and cognitive function in healthy adults.
Int J Geriatr Psychiatry,
33(2), e286-e293.
Abstract:
Online assessment of risk factors for dementia and cognitive function in healthy adults.
OBJECTIVE: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. METHOD: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. RESULTS: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. CONCLUSION: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan.
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Svendsboe EJ, Testad I, Terum T, Jörg A, Corbett A, Aarsland D, Rongve A (2018). Patterns of carer distress over time in mild dementia.
Int J Geriatr Psychiatry,
33(7), 987-993.
Abstract:
Patterns of carer distress over time in mild dementia.
OBJECTIVE: to study the level of carer reported distress in mild dementia, over a 3-year period. METHODS: This study is part of the Norwegian DemVest-study and utilises data from carers of people with mild dementia (n = 223). Those diagnosed with dementia with Lewy bodies (DLB, n = 63) and Alzheimer's disease (AD, n = 97) were included together with other dementia types (n = 63). The Relatives' Stress Scale was used to assess the level of reported distress in carers. Descriptive and a linear mixed effects models including diagnosis, time, and the interaction between time and diagnosis were performed. RESULTS: Carer distress in mild dementia increased significantly over time (P = 0.011), particularly from baseline until 2 (P = 0.001) years follow-up. Carer distress in people caring for those with AD increased significantly, from baseline until 2 (P = 0.047) and 3 (P = 0.019) years follow-up. Distress in carers of people with DLB was high at baseline and remained relatively stable across the 3-year period. However, admission to a nursing home during the first year of follow-up was associated with a significantly lower reported carer distress in those caring for a person with DLB (P = 0.002), compared with those caring for a person with DLB living at home. CONCLUSION: Being a carer to a person with mild dementia is associated with increasing distress. However, the burden of distress changes with the diagnosis, time, and situation, which highlights the dynamic nature of the caring role. Findings have important implications for health services for people diagnosed with mild dementia and their carers.
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Austbø Holteng LB, Frøiland CT, Corbett A, Testad I (2017). Care staff perspective on use of texture modified food in care home residents with dysphagia and dementia.
Ann Palliat Med,
6(4), 310-318.
Abstract:
Care staff perspective on use of texture modified food in care home residents with dysphagia and dementia.
BACKGROUND: Dysphagia and dementia are conditions, which combined, can lead to complications for the person and require good nutritional care. There is very little evidence-based literature regarding nutritional care for people with dysphagia and dementia. It is clear that care staff plays a vital role, and that communication and informed decision-making are critical to the process, yet little is known regarding the use of available interventions such as texture modified food (TMF), and their acceptability and feasibility for care staff and residents. Therefore the aim of this study was to investigate the experiences of care staff when providing nutritional care for people with dysphagia and dementia, and their impressions and experience of using TMF as a new intervention for nutrition. METHODS: This was a qualitative study with an inductive approach, which aimed to explore the experience of care staff using TMF in a care home setting. Data were collected using focus group interviews, an approach which is validated as a means of supporting and developing the understanding of a phenomenon, through interactions and discussions in the group. Participants were care staff working in a care home setting in Norway. RESULTS: Twelve participants were recruited to this study across two focus groups. The cohort included four nurses, six practical nurses, one nurse assistants and one student nurse. Four main categories emerged from the focus group discussions regarding the use of TMF. These were: (I) emotional strain; (II) deficient nutritional care; (III) increased self-efficacy with use of TMF; (IV) better nutritional care with TMF. CONCLUSIONS: Use of TMF to improve nutritional care for people with dysphagia appears to have merit for both residents and care staff, and should be considered as a means of improving nutritional care for people with dementia in care homes. Minimizing feeding difficulties and increasing nutritional intake is an important goal when caring for this vulnerable group of people, and there is a need to provide better training and support for care staff to ensure they feel confident and empowered to provide high quality nutritional care. The existing Norwegian Directorate of Health checklist for nutritional care may provide a helpful basis for improvements to guidance that accounts for the needs of staff and institutions. Further research and evaluation of an intervention for tailored nutritional care is warranted to improve this critical aspect of dementia care.
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Svendsboe E, Terum T, Testad I, Aarsland D, Ulstein I, Corbett A, Rongve A (2017). Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease (vol 31, pg 1075, 2016).
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
32(4), 470-470.
Author URL.
Khan A, Corbett A, Ballard C (2017). Emerging amyloid and tau targeting treatments for Alzheimer's disease.
Expert Rev Neurother,
17(7), 697-711.
Abstract:
Emerging amyloid and tau targeting treatments for Alzheimer's disease.
With an ageing global population, the number of people with dementia, and its main cause Alzheimer's disease (AD), is growing. current licensed treatments available for ad are only alleviate the symptoms of the disease, and are effective only in some people with ad for a limited time. there are currently no therapies that target the disease process. Areas covered: This review summarizes the available treatments for AD and the emerging therapies in the clinical trials pipeline. There are ongoing trials at various stages of development, targeting different mechanisms and pathways implicated in the disease. This review focuses on amyloid and tau targeting drug candidates. Expert commentary: Despite research efforts targeted at understanding AD, the underlying mechanisms and optimal treatment targets have not been fully elucidated. There is a significant need for further research targeting the disease at an earlier stage and progress in biomarker and imaging technology are improving the outlook. It is critical to continue research into identifying the underlying pathology and disease process in Alzheimer's disease to enable development of effective targeted treatments.
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Khan A, Corbett A, Ballard C (2017). Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
Expert Rev Neurother,
17(7), 683-695.
Abstract:
Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
The number of people with dementia, including Alzheimer's disease, is growing as a result of an ageing global population. Treatments available for AD only alleviate the symptoms of the disease, and are effective in some people with AD for a limited time. There is no disease-modifying treatment available, and despite research efforts, the underlying mechanisms of AD and optimal treatment targets have not been fully elucidated. Amyloid and tau are key pathological markers of AD with ongoing trials targeting both. However, there are also many trials at various stages of development that primarily target other markers and processes implicated in the disease, which are now being investigated. Areas covered: This review summarizes current treatment approaches for AD and explores both repositioned and novel therapies that target non amyloid and non tau mechanisms that are in the clinical trials pipeline. This includes treatments for cognitive and neuropsychiatric symptoms and potentially disease modifying therapies. The studies included in this review have been obtained from searches of PubMed and clinical trials databases. Expert commentary: There is a renewed energy in identifying better treatments for behavioural symptoms of AD using both novel drugs and repositioning existing drugs. Lack of success in clinical trials of drugs targeting amyloid and tau have led to a surge in targeting alternative mechanisms. Progress in the development of biomarkers will provide further tools for clinical trials of potential therapeutics for both symptomatic treatment and disease modification in AD.
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Rajkumar AP, Ballard C, Fossey J, Orrell M, Moniz-Cook E, Woods RT, Murray J, Whitaker R, Stafford J, Knapp M, et al (2017). Epidemiology of Pain in People with Dementia Living in Care Homes: Longitudinal Course, Prevalence, and Treatment Implications.
J Am Med Dir Assoc,
18(5), 453.e1-453.e6.
Abstract:
Epidemiology of Pain in People with Dementia Living in Care Homes: Longitudinal Course, Prevalence, and Treatment Implications.
INTRODUCTION: Knowledge regarding the longitudinal course, impact, or treatment implications of pain in people with dementia living in care homes is very limited. METHODS: We investigated the people with dementia living in 67 care homes in London and Buckinghamshire, United Kingdom. Pain, dementia severity, neuropsychiatric symptoms, depression, agitation, and quality-of-life were measured using appropriate instruments at baseline (N = 967) and after 9 months (n = 629). RESULTS: Baseline prevalence of pain was 35.3% (95% CI 32.3-38.3). Pain severity was significantly correlated with dementia severity, neuropsychiatric symptoms, depression, agitation, and quality of life at both time points. Regular treatment with analgesics significantly reduced pain severity. Pain was significantly associated with more antipsychotic prescriptions. Pain was significantly associated (OR 1.48; 95% CI 1.18-1.85) with all-cause mortality during follow-up. CONCLUSIONS: Pain is an important determinant of neuropsychiatric symptoms, mortality, quality-of-life, and antipsychotic prescriptions. Improved identification, monitoring, and treatment of pain are urgent priorities to improve the health and quality-of-life for people with dementia.
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Drageset J, Eide GE, Corbett A (2017). Health-related quality of life among cognitively intact nursing home residents with and without cancer - a 6-year longitudinal study.
Patient Relat Outcome Meas,
8, 63-69.
Abstract:
Health-related quality of life among cognitively intact nursing home residents with and without cancer - a 6-year longitudinal study.
BACKGROUND: Limited information exists regarding the natural development of health-related quality of life (HRQOL) and its determinants among mentally intact nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year period among residents of NHs, who are not cognitively impaired, and to examine whether sense of coherence and a diagnosis of cancer influence HRQOL. METHODS: the study was prospective and included baseline assessment and 6-year follow-up. After baseline assessment of 227 cognitively intact NH residents (Clinical Dementia Rating score ≤ 0.5), we interviewed 52 living respondents a second time at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up. We recorded data from the interviews using the Short Form-36 (SF-36) Health Survey and the Sense of Coherence Scale. To study different developments over time for residents without and with cancer, we tested interactions between cancer and time. RESULTS: the subscores of physical functioning and role limitation-physical domains declined with time (P < 0.001 and P = 0.02, respectively). Having a diagnosis of cancer at baseline was negatively correlated with general health (P = 0.002). Sense of coherence at baseline was positively correlated with all the SF-36 subscores from baseline to follow-up (P < 0.001). CONCLUSION: the study indicates that the HRQOL changed over time during the 6 years of follow-up, and the sense of coherence appeared to be an important component of the HRQOL. Finally, our results showed that having a diagnosis of cancer was associated with decline in the general health subdimension.
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Mueller C, Ballard C, Corbett A, Aarsland D (2017). Historical landmarks in dementia with Lewy bodies.
Lancet Neurol,
16(5).
Author URL.
Ballard C, Orrell M, Sun Y, Moniz-Cook E, Stafford J, Whitaker R, Woods B, Corbett A, Banerjee S, Testad I, et al (2017). Impact of antipsychotic review and non-pharmacological intervention on health-related quality of life in people with dementia living in care homes: WHELD-a factorial cluster randomised controlled trial.
Int J Geriatr Psychiatry,
32(10), 1094-1103.
Abstract:
Impact of antipsychotic review and non-pharmacological intervention on health-related quality of life in people with dementia living in care homes: WHELD-a factorial cluster randomised controlled trial.
BACKGROUND: Very few interventional studies have directly examined the impact of treatment approaches on health-related quality of life (HRQL) in people with dementia. This is of particular importance in therapies to address behavioural symptoms, where HRQL is often severely affected. METHODS: Analysis within the WHELD cluster randomised factorial study in 16 UK care homes examining the impact of person-centred care in combination with antipsychotic review, social interaction and exercise interventions. This study analysed impact on HRQL through the DEMQOL-Proxy. RESULTS: Data on HRQL were available for 187 participants. People receiving antipsychotic review showed a significant worsening in two DEMQOL-Proxy domains (negative emotion: p = 0.02; appearance: p = 0.04). A best-case scenario analysis showed significant worsening for total DEMQOL-Proxy score. Social interaction intervention resulted in a significant benefit to HRQL (p = 0.04). There was no deterioration in HRQL in groups receiving both antipsychotic review and social interaction (p = 0.62). CONCLUSIONS: This demonstrates an important detrimental impact of discontinuation of antipsychotics in dementia on HRQL, highlighting the need for careful review of best practice guidelines regarding antipsychotic use and emphasising the importance of providing evidence-based non-pharmacological interventions in conjunction with antipsychotic review. Copyright © 2016 John Wiley & Sons, Ltd.
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Gatt A, Ekonomou A, Somani A, Thuret S, Howlett D, Corbett A, Johnson M, Perry E, Attems J, Francis P, et al (2017). Importance of Proactive Treatment of Depression in Lewy Body Dementias: the Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study.
Dement Geriatr Cogn Disord,
44(5-6), 283-293.
Abstract:
Importance of Proactive Treatment of Depression in Lewy Body Dementias: the Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study.
OBJECTIVE: to examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). METHODS: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). RESULTS: DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. CONCLUSION: SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.
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Flo E, Bjorvatn B, Corbett A, Pallesen S, Husebo BS (2017). Joint Occurrence of Pain and Sleep Disturbances in People with Dementia. A Systematic Review.
Curr Alzheimer Res,
14(5), 538-545.
Abstract:
Joint Occurrence of Pain and Sleep Disturbances in People with Dementia. A Systematic Review.
BACKGROUND: Advancing age is associated with high prevalence of pain, sleep problems and dementia. Dementia is frequently accompanied by distressing behavioral and psychological symptoms, including sleep problems. The etiology of sleep problems in dementia is multifactorial. It has been suggested that untreated pain may contribute to sleep problems, and pain treatment has been shown to reduce sleep problems in people with dementia. OBJECTIVE: This systematic review aims to provide an overview of the studies that have investigated the association and/or possible interaction between pain and sleep in dementia. METHODS: a systematic search was performed in MEDLINE, EMBASE, Cochrane and PsychINFO, including text words and MESH terms covering dementia, pain and sleep. Also, reference lists in the included publications were examined to retrieve publications. Publications had to investigate sleep and pain in relation to dementia to be included in this review. RESULTS: the search produced 1750 independent hits. Out of the 49 publications studied in full text, 11 publications were included. Only one controlled trial was identified and represented the only insights to the possible interactional relationship between pain, sleep and dementia. Pain or pain intensity were related to sleep in 6 of the included studies, while the remaining studies could neither support nor contradict a relationship between sleep and pain in people with dementia. None of the studies employed objective sleep assessment. CONCLUSION: There is a need for high quality studies investigating the interaction between sleep and pain in people with dementia, using objective sleep measurements and pain assessment suitable for people with dementia.
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Mueller C, Ballard C, Corbett A, Aarsland D (2017). The prognosis of dementia with Lewy bodies.
Lancet Neurol,
16(5), 390-398.
Abstract:
The prognosis of dementia with Lewy bodies.
Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimer's disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimer's disease. It is probable that causative factors for this less favourable prognosis are the increased prevalence and early emergence of neuropsychiatric symptoms in patients with dementia with Lewy bodies, and the challenge of accurate diagnosis. Evidence concerning quality of life and hospital admission rates is limited, despite their clinical and economic relevance.
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Wesnes KA, Brooker H, Ballard C, McCambridge L, Stenton R, Corbett A (2017). Utility, reliability, sensitivity and validity of an online test system designed to monitor changes in cognitive function in clinical trials.
Int J Geriatr Psychiatry,
32(12), e83-e92.
Abstract:
Utility, reliability, sensitivity and validity of an online test system designed to monitor changes in cognitive function in clinical trials.
OBJECTIVE: the advent of long-term remotely conducted clinical trials requires assessments which can be administered online. This paper considers the utility, reliability, sensitivity and validity of an internet-based system for measuring changes in cognitive function which is being used in one such trial. METHODS: the Platform for Research Online to investigate Genetics and Cognition in Ageing is a 10-year longitudinal and entirely remote study launched in November 2015. The CogTrackTM System is being used to monitor changes in important aspects of cognitive function using tests of attention, information processing and episodic memory. On study entry, the participants performed CogTrackTM up to three times over seven days, and these data are evaluated in this paper. RESULTS: During the first six months of the study, 14 531 individuals aged 50 to 94 years enrolled and performed the CogTrackTM System, 8627 of whom completed three test sessions. On the first administration, 99.4% of the study tasks were successfully completed. Repeated testing showed training/familiarisation effects on four of the ten measures which had largely stabilised by the third test session. The factor structure of the various measures was found to be robust. Evaluation of the influence of age identified clinically relevant declines over the age range of the population on one or more measures from all tasks. CONCLUSIONS: the results of these analyses identify CogTrackTM to be a practical and valid method to reliably, sensitively, remotely and repeatedly collect cognitive data from large samples of individuals aged 50 and over. Copyright © 2017 John Wiley & Sons, Ltd.
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Clare L, Kudlicka A, Bayer A, Jones RW, John Knapp MR, Kopelman M, Leroi I, Oyebode J, Pool J, Woods B, et al (2017). [O3–02–05]: GOAL‐ORIENTED COGNITIVE REHABILITATION IN EARLY‐STAGE ALZHEIMER's AND RELATED DEMENTIAS: RESULTS FROM a MULTI‐CENTRE, SINGLE‐BLIND, RANDOMISED CONTROLLED TRIAL (THE GREAT TRIAL). Alzheimer's & Dementia, 13(7S_Part_18).
Greenan C, Murphy L, Yu L-M, Kehoe PG, Coulthard E, Bath P, Stewart R, Jones R, Corbett A, Thomas A, et al (2016). A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
Trials,
17(1).
Abstract:
A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
BACKGROUND: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia. METHODS/DESIGN: This is a randomised controlled trial of calcium channel blockade with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks. DISCUSSION: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31208535. Registered on 7 March 2014.
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Rajkumar AP, Ballard C, Fossey J, Corbett A, Woods B, Orrell M, Prakash R, Moniz-Cook E, Testad I (2016). Apathy and its Response to Antipsychotic Review and Nonpharmacological Interventions in People with Dementia Living in Nursing Homes: WHELD, a Factorial Cluster Randomized Controlled Trial.
Journal of the American Medical Directors Association,
17(8), 741-747.
Abstract:
Apathy and its Response to Antipsychotic Review and Nonpharmacological Interventions in People with Dementia Living in Nursing Homes: WHELD, a Factorial Cluster Randomized Controlled Trial
Objectives Apathy is common, impactful, and difficult to manage in people with dementia. We evaluated the efficacy of nonpharmacological interventions, exercise, and social interaction, in combination with antipsychotic review, to reduce apathy in people with dementia living in nursing homes in a cluster randomized controlled trial (RCT). Methods Well-being and health for people with dementia (WHELD) program included a 2 × 2 × 2 factorial cluster RCT involving people with dementia living in 16 nursing homes in the United Kingdom. All homes received training in person-centered care, and were randomized to receive antipsychotic review, social interaction, and exercise, either alone or in combinations. Apathy was one of the secondary outcomes of the WHELD trial, and it was measured by the Neuropsychiatric Inventory–nursing home version at baseline and 9 months (n = 273). We used multilevel mixed effects linear regression models to assess the impact of the interventions on apathy. Results Prevalence of apathy was 44.0% (n = 120; 95% confidence interval [CI] 38.1%–49.9%) at baseline. Severity of apathy had significant positive correlations with dementia severity, neuropsychiatric symptoms, depressive symptoms, agitation, and the needs of the people with dementia (P
Abstract.
Svendsboe E, Terum T, Testad I, Aarsland D, Ulstein I, Corbett A, Rongve A (2016). Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease.
Int J Geriatr Psychiatry,
31(9), 1075-1083.
Abstract:
Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease.
OBJECTIVE: to characterise the differences in caregiver distress between carers of people diagnosed with dementia with Lewy bodies (DLB) and people with Alzheimer's disease (AD), with a view to differentiating and improving support for caregivers. METHODS: This study is a part of two larger Norwegian studies, DemVest (n = 265) and the Norwegian Dementia Register (n = 2220), with data from caregivers and people diagnosed with AD (n = 100) and DLB (n = 86) between 2005 and 2013. The average age was 74.9 years (SD = 7.8). Caregiver distress was rated by the Relative Stress Scale. Diagnosis of the person receiving care was based on a comprehensive standardised assessment program (International Classification of Diseases, Revision 10 or Diagnostic and Statistical Manual for Mental Disorders, fourth edition). Additional data collected from people receiving care were neuropsychiatric symptoms, comorbidity and activities of daily living (ADL) score. Linear regression analyses were applied, first unadjusted and then in stepwise-adjusts in addition to descriptive analyses. RESULTS: Caregivers to people with AD (20.2%) and 40% of caregivers for people with DLB experienced moderate or high caregiver burden with an increased risk of psychiatric disorders in the early stage of dementia. High Relative Stress Scale (RSS) total scores in caregivers was significantly associated with neuropsychiatric symptoms (Neuropsychiatric Inventory, p = 0.004) and also with impaired ADL functioning (Rapid Disability Rating Scale-2, p
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Ballard C, Mobley W, Hardy J, Williams G, Corbett A (2016). Dementia in Down's syndrome.
Lancet Neurol,
15(6), 622-636.
Abstract:
Dementia in Down's syndrome.
Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches.
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Corbett A, Ballard C (2016). Dextromethorphan and quinidine are suitable for off-label short-term treatment of agitation in people with Alzheimer's disease following first-line non-drug approaches.
Evid Based Med,
21(1).
Author URL.
Surr CA, Walwyn REA, Lilley-Kelly A, Cicero R, Meads D, Ballard C, Burton K, Chenoweth L, Corbett A, Creese B, et al (2016). Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial.
Trials,
17(1).
Abstract:
Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial.
BACKGROUND: up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. METHODS/DESIGN: a pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. DISCUSSION: the protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015.
Abstract.
Author URL.
Ballard C, Orrell M, YongZhong S, Moniz-Cook E, Stafford J, Whittaker R, Woods B, Corbett A, Garrod L, Khan Z, et al (2016). Impact of Antipsychotic Review and Nonpharmacological Intervention on Antipsychotic Use, Neuropsychiatric Symptoms, and Mortality in People with Dementia Living in Nursing Homes: a Factorial Cluster-Randomized Controlled Trial by the Well-Being and Health for People with Dementia (WHELD) Program.
Am J Psychiatry,
173(3), 252-262.
Abstract:
Impact of Antipsychotic Review and Nonpharmacological Intervention on Antipsychotic Use, Neuropsychiatric Symptoms, and Mortality in People with Dementia Living in Nursing Homes: a Factorial Cluster-Randomized Controlled Trial by the Well-Being and Health for People with Dementia (WHELD) Program.
OBJECTIVE: This study evaluated the impact of antipsychotic review, social interaction, and exercise, in conjunction with person-centered care, on antipsychotic use, agitation, and depression in people with dementia living in nursing homes. METHOD: a cluster-randomized factorial controlled trial with two replications was conducted in people with dementia in 16 U.K. nursing homes. All homes received training in person-centered care. Eight homes were randomly assigned to antipsychotic review, to a social interaction intervention, and to an exercise intervention for 9 months, with most homes assigned to more than one intervention. The primary outcome measures were antipsychotic use, agitation, and depression. Secondary outcome measures were overall neuropsychiatric symptoms and mortality. RESULTS: Antipsychotic review significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval [CI] 0.05 to 0.60). Antipsychotic review plus the social interaction intervention significantly reduced mortality (odds ratio 0.26, 95% CI 0.13 to 0.51) compared with the group receiving neither. The group receiving antipsychotic review but not the social intervention showed significantly worse outcome in neuropsychiatric symptoms compared with the group receiving neither (score difference +7.37, 95% CI 1.53 to 13.22). This detrimental impact was mitigated by concurrent delivery of the social intervention (-0.44, CI -4.39 to 3.52). The exercise intervention significantly improved neuropsychiatric symptoms (-3.59, 95% CI -7.08 to -0.09) but not depression (-1.21, CI -4.35 to 1.93). None of the interventions had a significant impact specifically on agitation. CONCLUSIONS: While reductions in antipsychotic use can be achieved by using a "real world" intervention, this may not be of benefit to people with dementia in the current climate of more judicious prescribing unless nonpharmacological interventions such as social interaction or exercise are provided in parallel.
Abstract.
Author URL.
Lichtner V, Dowding D, Allcock N, Keady J, Sampson EL, Briggs M, Corbett A, James K, Lasrado R, Swarbrick C, et al (2016). The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective.
BMC Health Serv Res,
16(1).
Abstract:
The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective.
BACKGROUND: Pain is often poorly managed in people who have a dementia. Little is known about how this patient population is managed in hospital, with research to date focused mainly on care homes. This study aimed to investigate how pain is recognised, assessed and managed in patients with dementia in a range of acute hospital wards, to inform the development of a decision support tool to improve pain management for this group. METHODS: a qualitative, multi-site exploratory case study. Data were collected in four hospitals in England and Scotland. Methods included non-participant observations, audits of patient records, semi-structured interviews with staff and carers, and analysis of hospital ward documents. Thematic analysis was performed through the lens of decision making theory. RESULTS: Staff generally relied on patients' self-report of pain. For patients with dementia, however, communication difficulties experienced because of their condition, the organisational context, and time frames of staff interactions, hindered patients' ability to provide staff with information about their pain experience. This potentially undermined the trials of medications used to provide pain relief to each patient and assessments of their responses to these treatments. Furthermore, given the multidisciplinary environment, a patient's communication about their pain involved several members of staff, each having to make sense of the patient's pain as in an 'overall picture'. Information about patients' pain, elicited in different ways, at different times and by different health care staff, was fragmented in paper-based documentation. Re-assembling the pieces to form a 'patient specific picture of the pain' required collective staff memory, 'mental computation' and time. CONCLUSIONS: There is a need for an efficient method of eliciting and centralizing all pain-related information for patients with dementia, which is distributed in time and between personnel. Such a method should give an overall picture of a patient's pain which is rapidly accessible to all involved in their care. This would provide a much-needed basis for making decisions to support the effective management of the pain of older people with dementia in hospital.
Abstract.
Author URL.
Corbett A, Nunez K-M, Smeaton E, Testad I, Thomas AJ, Closs SJ, Briggs M, Clifton L, Gjestsen MT, Lawrence V, et al (2016). The landscape of pain management in people with dementia living in care homes: a mixed methods study.
Int J Geriatr Psychiatry,
31(12), 1354-1370.
Abstract:
The landscape of pain management in people with dementia living in care homes: a mixed methods study.
OBJECTIVES: the aim of this study is to explore the current landscape of pain management in people with dementia living in care home settings. Pain is extremely common in this patient group, yet there is very limited guidance for healthcare professionals. METHODS: Triangulation of stakeholder consultation and quality review of pain management guidance were performed. A review of existing pain management guidance was conducted using published quality criteria adapted for the field. Three focus group discussions were held with care home staff and two focus group discussions and an online survey with family carers. Data were subjected to thematic analysis to identify themes and sub-themes. Outcomes were reviewed by an expert panel, which gave recommendations. RESULTS: Fifteen existing guidelines were identified, of which three were designed for use in dementia and none were tailored for care home settings. Thematic analysis revealed six major themes in current pain management in dementia: importance of person-centredness, current lack of pain awareness in staff, communication as a core element, disparities in staff responsibility and confidence, the need for consistency of care and current lack of staff training. In addition to the needs for practice, the expert panel identified promising pharmacological treatment candidates, which warrant clinical evaluation. CONCLUSIONS: the findings of this study clearly articulate a need for an evidence-based pain management programme for care homes, which is informed by stakeholder input and based within a conceptual framework for this setting. There are novel opportunities for clinical trials of alternative analgesics for use in this patient group. Copyright © 2016 John Wiley & Sons, Ltd.
Abstract.
Author URL.
Closs SJ, Dowding D, Allcock N, Hulme C, Keady J, Sampson EL, Briggs M, Corbett A, Esterhuizen P, Holmes J, et al (2016). Towards improved decision support in the assessment and management of pain for people with dementia in hospital: a systematic meta-review and observational study.
Health Services and Delivery Research,
4(30), 1-162.
Abstract:
Towards improved decision support in the assessment and management of pain for people with dementia in hospital: a systematic meta-review and observational study
BackgroundPain and dementia are common in older people, and impaired cognitive abilities make it difficult for them to communicate their pain. Pain, if poorly managed, impairs health and well-being. Accurate pain assessment in this vulnerable group is challenging for hospital staff, but essential for appropriate management. Robust methods for identifying, assessing and managing pain are needed.Aims and objectivesTwo studies were undertaken to inform the development of a decision support tool to aid hospital staff in the recognition, assessment and management of pain. The first was a meta-review of systematic reviews of observational pain assessment instruments with three objectives: (1) to identify the tools available to assess pain in adults with dementia; (2) to identify in which settings they were used and with what patient populations; and (3) to assess their reliability, validity and clinical utility. The second was a multisite observational study in hospitals with four objectives: (1) to identify information currently used by clinicians when detecting and managing pain in patients with dementia; (2) to explore existing processes for detecting and managing pain in these patients; (3) to identify the role (actual/potential) of carers in this process; and (4) to explore the organisational context in which health professionals operate. Findings also informed development of health economics data collection forms to evaluate the implementation of a new decision support intervention in hospitals.MethodsFor the meta-review of systematic reviews, 12 databases were searched. Reviews of observational pain assessment instruments that provided psychometric data were included. Papers were quality assessed and data combined using narrative synthesis. The observational study used an ethnographic approach in 11 wards in four UK hospitals. This included non-participant observation of 31 patients, audits of patient records, semistructured interviews with 52 staff and four carers, informal conversations with staff and carers and analysis of ward documents and policies. Thematic analysis of the data was undertaken by the project team.ResultsData from eight systematic reviews including 28 tools were included in the meta-review. Most tools showed moderate to good reliability, but information about validity, feasibility and clinical utility was scarce. The observational study showed complex ward cultures and routines, with variations in time spent with patients, communication patterns and management practices. Carer involvement was rare. No pain decision support tools were observed in practice. Information about pain was elicited in different ways, at different times, by different health-care staff and recorded in separate documents. Individual staff made sense of patients’ pain by creating their own ‘overall picture’ from available information.LimitationsGrey literature and non-English-language papers were excluded from the meta-review. Sample sizes in the observational study were smaller than planned owing to poor documentation of patients’ dementia diagnoses, gatekeeping by staff and difficulties in gaining consent/assent. Many patients had no or geographically distant carers, or a spouse who was too unwell and/or reluctant to participate.ConclusionsNo single observational pain scale was clearly superior to any other. The traditional linear concept of pain being assessed, treated and reassessed by single individuals did not ‘fit’ with clinical reality. A new approach enabling effective communication among patients, carers and staff, centralised recording of pain-related information, and an extended range of pain management interventions is proposed [Pain and Dementia Decision Support (PADDS)]. This was not tested with users, but a follow-on study aims to codesign PADDS with carers and clinicians, then introduce education on staff/patient/carer communications and use of PADDS within a structured implementation plan. PADDS will need to be tested in differing ward contexts.FundingThe National Institute for Health Research Health Services and Delivery Research programme.
Abstract.
Khan A, Kalaria RN, Corbett A, Ballard C (2016). Update on Vascular Dementia.
J Geriatr Psychiatry Neurol,
29(5), 281-301.
Abstract:
Update on Vascular Dementia.
Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment.
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Ballard C, Thomas A, Gerry S, Yu L-M, Aarsland D, Merritt C, Corbett A, Davison C, Sharma N, Khan Z, et al (2015). A Double-Blind Randomized Placebo-Controlled Withdrawal Trial Comparing Memantine and Antipsychotics for the Long-Term Treatment of Function and Neuropsychiatric Symptoms in People with Alzheimer's Disease (MAIN-AD).
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION,
16(4), 316-322.
Author URL.
Ferreira N, Owen A, Mohan A, Corbett A, Ballard C (2015). Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
30(4), 422-430.
Author URL.
Ballard C, Sharp S, Corbett A (2015). Dextromethorphan and Quinidine for Treating Agitation in Patients with Alzheimer Disease Dementia.
JAMA,
314(12), 1233-1235.
Author URL.
Corbett A (2015). Drug repositioning in Alzheimer rsquo s disease. Frontiers in Bioscience, 7(1), 184-188.
Corbett A, Williams G, Ballard C (2015). Drug repositioning in Alzheimer's disease.
Front Biosci (Schol Ed),
7(1), 184-188.
Abstract:
Drug repositioning in Alzheimer's disease.
Drug repositioning offers an innovative approach to drug discovery with great potential in the field of Alzheimer's Disease and dementia therapeutics. Investigation of licensed compounds enables processing through the drug discovery pipeline in a rapid and cost-effective manner. A growing body of evidence supports the translation of priority compounds to be taken forward to clinical trials, based on established and proposed mechanisms of action. A number of drugs have already entered clinical trial following repositioning, and novel technologies have been created to enable high-throughput screening. This review discusses the novel approaches that build on transcriptional signature profiling to support repositioning in AD, and the novel candidate drugs that are emerging from this exciting new technique.
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Creese B, Corbett A, DPhil EJ, Fox C, Ballard C (2015). Erratum to [Role of the Extended MAPT Haplotype in the Worsening of Psychotic Symptoms and Treatment Response in Alzheimer Disease, J Am Med Dir Assoc, 15, 12, (2014), 934-937], DOI: 10.1016/j.jamda.2014.08.011. Journal of the American Medical Directors Association, 16(3).
Ballard C, Isaacson S, Mills R, Williams H, Corbett A, Coate B, Pahwa R, Rascol O, Burn DJ (2015). Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People with Parkinson Disease Psychosis.
J Am Med Dir Assoc,
16(10), 898.e1-898.e7.
Abstract:
Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People with Parkinson Disease Psychosis.
OBJECTIVES: to establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. DESIGN: Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. SETTING: Primary and secondary care medical centers in the United States, Canada, Europe, and India. PARTICIPANTS: a total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. INTERVENTIONS: Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. MAIN OUTCOME MEASURES: Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. CONCLUSIONS: This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality.
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Author URL.
Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, et al (2015). The Effect of an Online Cognitive Training Package in Healthy Older Adults: an Online Randomized Controlled Trial.
Journal of the American Medical Directors Association,
16(11), 990-997.
Author URL.
Ballard C, Corbett A, Sharp S (2014). Aligning the evidence with practice: NICE guidelines for drug treatment of Alzheimer’s disease. Expert Review of Neurotherapeutics, 11(3), 327-329.
Corbett A, Achterberg W, Husebo B, Lobbezoo F, de Vet H, Kunz M, Strand L, Constantinou M, Tudose C, Kappesser J, et al (2014). An international road map to improve pain assessment in people with impaired cognition: the development of the Pain Assessment in Impaired Cognition (PAIC) meta-tool.
BMC Neurol,
14Abstract:
An international road map to improve pain assessment in people with impaired cognition: the development of the Pain Assessment in Impaired Cognition (PAIC) meta-tool.
BACKGROUND: Pain is common in people with dementia, yet identification is challenging. A number of pain assessment tools exist, utilizing observation of pain-related behaviours, vocalizations and facial expressions. Whilst they have been developed robustly, these often lack sufficient evidence of psychometric properties, like reliability, face and construct validity, responsiveness and usability, and are not internationally implemented. The EU-COST initiative "Pain in impaired cognition, especially dementia" aims to combine the expertise of clinicians and researchers to address this important issue by building on previous research in the area, identifying existing pain assessment tools for dementia, and developing consensus for items for a new universal meta-tool for use in research and clinical settings. This paper reports on the initial phase of this collaboration task. METHODS: all existing observational pain behaviour tools were identified and elements categorised using a three-step reduction process. Selection and refinement of items for the draft Pain Assessment in Impaired Cognition (PAIC) meta-tool was achieved through scrutiny of the evidence, consensus of expert opinion, frequency of use and alignment with the American Geriatric Society guidelines. The main aim of this process was to identify key items with potential empirical, rather than theoretical value to take forward for testing. RESULTS: 12 eligible assessment tools were identified, and pain items categorised according to behaviour, facial expression and vocalisation according to the AGS guidelines (Domains 1 - 3). This has been refined to create the PAIC meta-tool for validation and further refinement. A decision was made to create a supporting comprehensive toolkit to support the core assessment tool to provide additional resources for the assessment of overlapping symptoms in dementia, including AGS domains four to six, identification of specific types of pain and assessment of duration and location of pain. CONCLUSIONS: This multidisciplinary, cross-cultural initiative has created a draft meta-tool for capturing pain behaviour to be used across languages and culture, based on the most promising items used in existing tools. The draft PAIC meta-tool will now be taken forward for evaluation according to COSMIN guidelines and the EU-COST protocol in order to exclude invalid items, refine included items and optimise the meta-tool.
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Author URL.
Sultana J, Chang CK, Hayes RD, Broadbent M, Stewart R, Corbett A, Ballard C (2014). Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study. International Journal of Geriatric Psychiatry, 29(12), 1249-1254.
Drageset J, Corbett A, Selbaek G, Husebo BS (2014). Cancer-related pain and symptoms among nursing home residents: a systematic review.
J Pain Symptom Manage,
48(4), 699-710.e1.
Abstract:
Cancer-related pain and symptoms among nursing home residents: a systematic review.
CONTEXT: Many older nursing home (NH) residents with cancer experience pain and distressing symptoms. Although some develop cancer during their time in the institution, an increasing number are admitted during their final stages of their lives. Numerous studies have evaluated various treatment approaches, but how pain and symptoms are assessed and managed in people with cancer with and without dementia is unclear. OBJECTIVES: the objective of this review was to summarize the evidence on cancer-related symptoms among NH residents with and without dementia. METHODS: We systematically searched the PubMed (1946-2012), Embase (1974-2012), CINAHL (1981-2012), AgeLine, and Cochrane Library (1998-2012) databases using the search terms neoplasms, cancer, tumor, and nursing home. The inclusion criteria were studies including NH residents with a diagnosis of cancer and outcome measures including pain and cancer-related symptoms. RESULTS: We identified 11 studies (cross-sectional, longitudinal, clinical trial, and qualitative studies). Ten studies investigated the prevalence and treatment of cancer-related symptoms such as vomiting, nausea, urinary tract infections, and depression. Studies clearly report a high prevalence of pain and reduced prescribing and treatment, regardless of the cognitive status. Only one small study included people with cancer and a diagnosis of dementia. Studies of new cancer diagnoses in NHs could not be identified. CONCLUSION: This review clearly reports a high prevalence of pain and reduced drug prescribing and treatment among NH residents with cancer. This issue appears to be most critical among people with severe dementia, emphasizing the need for better guidance and evidence on pain assessment for these individuals.
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Author URL.
Khan Z, Corbett A, Ballard C (2014). Cognitive stimulation therapy: training, maintenance and implementation in clinical trials.
Pragmat Obs Res,
5, 15-19.
Abstract:
Cognitive stimulation therapy: training, maintenance and implementation in clinical trials.
There are around 35 million people worldwide with dementia, more than half of whom have Alzheimer's disease (AD). Presently there are only four licensed pharmacological treatments available for treating the neuropsychological symptoms of AD. These include cholinesterase inhibitors, licensed for the treatment of people with mild to moderate AD, and an N-methyl-D-aspartate antagonist (memantine) licensed for the treatment of people with moderate to severe AD. These treatment options have modest symptomatic benefits for at least 6 months and possibly for 2 years or longer. Increasing evidence from randomized controlled trials has shown the potential value of cognitive training and cognitive rehabilitation in people with AD. There is a good evidence base to support the use of cognitive stimulation as a nonpharmacological treatment approach for people with AD, of which the most promising is cognitive stimulation therapy (CST). CST has shown benefits for cognition and well-being in people with dementia across a number of randomized controlled trials. There are important key issues related to the use of CST for people with AD, such as long-term benefits, implementation of individualized CST, adjunctive benefits with pharmacological treatments, and optimizing overall implementation of CST. Some of these key issues are already being addressed by ongoing clinical trials. Nevertheless, the strength of the current evidence from randomized controlled trials gives strong support to clinical implementation of CST in practice. Ongoing clinical trials will help to refine and optimize the use of CST in clinical practice.
Abstract.
Author URL.
Husebo BS, Corbett A (2014). Dementia: Pain management in dementia--the value of proxy measures.
Nat Rev Neurol,
10(6), 313-314.
Author URL.
Corbett A, Burns A, Ballard C (2014). Don't use antipsychotics routinely to treat agitation and aggression in people with dementia.
BMJ,
349 Author URL.
Ballard C, Aarsland D, Francis P, Corbett A (2014). Erratum to: Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: Pathophysiology, clinical features, and pharmacological management (Drugs Aging (2013) 30, (603-611) DOI: 10.1007/s40266-013-0092-x). Drugs and Aging, 31(8).
Testad I, Corbett A, Aarsland D, Lexow KO, Fossey J, Woods B, Ballard C (2014). Erratum: the value of personalized psychosocial interventions to address behavioral and psychological symptoms in people with dementia living in care home settings: a systematic review (International Psychogeriatrics (2014) DOI; 10.1017/S1041610214000131)). International Psychogeriatrics, 26(7).
Sandvik RK, Selbaek G, Seifert R, Aarsland D, Ballard C, Corbett A, Husebo BS (2014). Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: a cluster randomized trial.
Eur J Pain,
18(10), 1490-1500.
Abstract:
Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: a cluster randomized trial.
BACKGROUND: Pain is frequent and distressing in people with dementia, but no randomized controlled trials have evaluated the effect of analgesic treatment on pain intensity as a key outcome. METHODS: Three hundred fifty-two people with dementia and significant agitation from 60 nursing home units were included in this study. These units, representing 18 nursing homes in western Norway, were randomized to a stepwise protocol of treating pain (SPTP) or usual care. The SPTP group received acetaminophen, morphine, buprenorphine transdermal patch and pregabalin for 8 weeks, with a 4-week washout period. Medications were governed by the SPTP and each participant's existing prescriptions. We obtained pain intensity scores from 327 patients (intervention n = 164, control n = 163) at five time points assessed by the primary outcome measure, Mobilization-Observation-Behaviour-Intensity-Dementia-2 (MOBID-2) Pain Scale. The secondary outcome was activities of daily living (ADL). We used a linear intercept mixed model in a two-way repeated measures configuration to assess change over time and between groups. RESULTS: the SPTP conferred significant benefit in MOBID-2 scores compared with the control group [average treatment effect (ATE) -1.388; p < 0.001] at week 8, and MOBID-2 scores worsened during the washout period (ATE = -0.701; p = 0.022). Examining different analgesic treatments, benefit was conferred to patients receiving acetaminophen compared with the controls at week 2 (ATE = -0.663; p = 0.010), continuing to increase until week 8 (ATE = -1.297; p < 0.001). Although there were no overall improvements in ADL, an increase was seen in the group receiving acetaminophen (ATE = +1.0; p = 0.022). CONCLUSION: Pain medication significantly improved pain in the intervention group, with indications that acetaminophen also improved ADL function.
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Author URL.
Broadstock M, Ballard C, Corbett A (2014). Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies.
Expert Opin Pharmacother,
15(13), 1797-1810.
Abstract:
Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies.
INTRODUCTION: Alzheimer's disease (AD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) together account for the vast majority of individuals with dementia. Approximately 35 million people worldwide are affected with this condition, and despite decades of research, effective therapies that slow or reverse disease progression have not yet been developed. The recent failure of several large-scale clinical trials is beginning to challenge the magnitude of focus on amyloid-related therapies for AD, and newer drug targets that have shown promise in the laboratory are being investigated in clinical trials. AREAS COVERED: This review summarises the current understanding of the underlying biology of AD, PDD and DLB and outlines the most recent drug candidates in advanced clinical trials. EXPERT OPINION: the lack of success in drug discovery for disease-modifying therapies for AD, PDD and DLB can be attributed to limitations in the design of clinical trials and the narrow focus of molecular targets for treatment. New avenues for drug discovery including repositioning and novel target identification may now provide opportunities for success, provided a critical mass of clinical trials is achieved through increased investment.
Abstract.
Author URL.
Corbett A, Smith J, Ballard C (2014). New and emerging treatments for Alzheimer’s disease. Expert Review of Neurotherapeutics, 12(5), 535-543.
Broadstock M, Ballard C, Corbett A (2014). Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease.
Expert Rev Clin Pharmacol,
7(6), 779-786.
Abstract:
Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease.
Parkinson's disease (PD) affects 10 million people worldwide. Half will develop psychosis, the majority experiencing hallucinations rather than delusions. Emergence of psychosis increases the likelihood of institutionalization and mortality. Where pharmacological treatment is warranted, options are limited. Most currently licensed atypical antipsychotics are ineffective or worsen motor symptoms in people with PD. This review of provides an overview of the current landscape of treatments and the opportunities in emerging research. Clozapine is the only licensed antipsychotic with proven efficacy, although the associated side effects limit its use. With recent advances in understanding the role of serotonin, rational drug design approaches have delivered a novel pharmacological treatment with recently proven efficacy in clinical trials of people with PD and psychosis. Pimavanserin represents an important addition to treatment.
Abstract.
Author URL.
Lichtner V, Dowding D, Esterhuizen P, Closs SJ, Long AF, Corbett A, Briggs M (2014). Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.
BMC Geriatr,
14Abstract:
Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.
BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence.
Abstract.
Author URL.
Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C (2014). Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial.
Lancet,
383(9916), 533-540.
Abstract:
Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial.
BACKGROUND: Parkinson's disease psychosis, which includes hallucinations and delusions, is frequent and debilitating in people with Parkinson's disease. We aimed to assess safety and efficacy of pimavanserin, a selective serotonin 5-HT2A inverse agonist, in this population. METHODS: in our 6 week, randomised, double-blind, placebo-controlled study, we enrolled adults (aged ≥40 years) with Parkinson's disease psychosis. Antipsychotic treatments were not permitted during the study, but controlled antiparkinsonian medication or deep brain stimulation was allowed. Eligible participants entered a 2 week non-pharmacological lead-in phase to limit the placebo response, after which they were randomly allocated (1:1) to receive pimavanserin 40 mg per day or matched placebo. The primary outcome was antipsychotic benefit as assessed by central, independent raters with the Parkinson's disease-adapted scale for assessment of positive symptoms (SAPS-PD) in all patients who received at least one dose of study drug and had a SAPS assessment at baseline and at least one follow-up. We assessed safety and tolerability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01174004. FINDINGS: Between Aug 11, 2010, and Aug 29, 2012, we randomly allocated 199 patients to treatment groups. For 90 recipients of placebo and 95 recipients of pimavanserin included in the primary analysis, pimavanserin was associated with a -5·79 decrease in SAPS-PD scores compared with -2·73 for placebo (difference -3·06, 95% CI -4·91 to -1·20; p=0·001; Cohen's d 0·50). Ten patients in the pimavanserin group discontinued because of an adverse event (four due to psychotic disorder or hallucination within 10 days of start of the study drug) compared with two in the placebo group. Overall, pimavanserin was well tolerated with no significant safety concerns or worsening of motor function. INTERPRETATION: Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist. The trial design used in this study to manage placebo response could have applicability to other studies in neuropsychiatric disease. FUNDING: ACADIA Pharmaceuticals.
Abstract.
Author URL.
Ballard C, Corbett A, Howard R (2014). Prescription of antipsychotics in people with dementia.
Br J Psychiatry,
205(1), 4-5.
Author URL.
Ballard C, Francis P, Corbett A (2014). Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies - ADDENDUM.
Int Psychogeriatr Author URL.
Creese B, Corbett A, Jones E, Fox C, Ballard C (2014). Role of the Extended MAPT Haplotype in the Worsening of Psychotic Symptoms and Treatment Response in Alzheimer Disease. Journal of the American Medical Directors Association, 15(12), 934-937.
Ballard C, Corbett A (2014). Screening for dementia: an opportunity for debate. Expert Review of Neurotherapeutics, 11(10), 1347-1349.
Fossey J, Masson S, Stafford J, Lawrence V, Corbett A, Ballard C (2014). The disconnect between evidence and practice: a systematic review of person-centred interventions and training manuals for care home staff working with people with dementia.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
29(8), 797-807.
Author URL.
Corbett A, Husebo BS, Achterberg WP, Aarsland D, Erdal A, Flo E (2014). The importance of pain management in older people with dementia.
Br Med Bull,
111(1), 139-148.
Abstract:
The importance of pain management in older people with dementia.
INTRODUCTION: Pain is common in people with dementia, representing a critical aspect of treatment and care. However, there remain considerable gaps in evidence to support pain assessment and treatment. SOURCES OF DATA: an updated literature search focussing on systematic reviews and randomized controlled trials. AREAS OF AGREEMENT: There are key areas of consistency around the prevalence, causes and current treatment trends for pain in dementia, the impact of untreated pain and the need for an accurate, fully validated assessment tool. AREAS OF CONTROVERSY: Accurate assessment due to inherent issues in dementia is a critical challenge. There is also a lack of evidence around alternative treatment options. GROWING POINTS: New pain predictors are being identified, including physical function, depression and specific pain types, which should inform assessment methodology. AREAS TIMELY FOR DEVELOPING RESEARCH: Future research should focus on developing integrated pain management approaches with optimized assessment and evidence-based treatment guidance.
Abstract.
Author URL.
Testad I, Corbett A, Aarsland D, Lexow KO, Fossey J, Woods B, Ballard C (2014). The value of personalized psychosocial interventions to address behavioral and psychological symptoms in people with dementia living in care home settings: a systematic review.
INTERNATIONAL PSYCHOGERIATRICS,
26(7), 1083-1098.
Author URL.
Corbett A, Ballard C (2014). The value of vitamin E as a treatment for Alzheimer's disease remains unproven despite functional improvement, due to a lack of established effect on cognition or other outcomes from RCTs. Evidence Based Medicine, 19(4), 140-140.
Ballard C, Corbett A (2013). Agitation and aggression in people with Alzheimer's disease. Current Opinion in Psychiatry, 26(3), 252-259.
Corbett A, Nunez K, Thomas A (2013). Coping with dementia in care homes. Maturitas, 76(1), 3-4.
Corbett A, Husebo B, Malcangio M, Staniland A, Cohen-Mansfield J, Aarsland D, Ballard C (2013). Correction: Assessment and treatment of pain in people with dementia. Nature Reviews Neurology, 9(7), 358-358.
Ballard C, Jones E, Gauge N, Aarsland D, Nilsen OB, Saxby BK, Lowery D, Corbett A, Wesnes K, Katsaiti E, et al (2013). Correction: Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PLoS ONE, 8(9).
Corbett A, Williams G, Ballard C (2013). Drug Repositioning: an Opportunity to Develop Novel Treatments for Alzheimer’s Disease. Pharmaceuticals, 6(10), 1304-1321.
Corbett A, Smith J, Ballard C (2013). Erratum: New and emerging treatments for Alzheimer's disease (Expert Review of Neurotherapeutics (2012) 12:5 (533-543) DOI: 10.1586/ern.12.43). Expert Review of Neurotherapeutics, 13(7).
Corbett A, Smith J, Ballard C (2013). Erratum: New and emerging treatments for Alzheimer's disease (Expert Review of Neurotherapeutics (2012) 12:5 (535-543)). Expert Review of Neurotherapeutics, 13(6).
Clare L, Bayer A, Burns A, Corbett A, Jones R, Knapp M, Kopelman M, Kudlicka A, Leroi I, Oyebode J, et al (2013). Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT).
Trials,
14Abstract:
Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT).
BACKGROUND: Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer's disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. METHODS/DESIGN: in this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. DISCUSSION: If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion.
Abstract.
Author URL.
Corbett A, Ballard C (2013). Is a potential Alzheimer's therapy already in use for other conditions? can medications for hypertension, diabetes and acne help with the symptoms?. Expert Opinion on Investigational Drugs, 22(8), 941-943.
Ballard C, Aarsland D, Francis P, Corbett A (2013). Neuropsychiatric Symptoms in Patients with Dementias Associated with Cortical Lewy Bodies: Pathophysiology, Clinical Features, and Pharmacological Management. Drugs & Aging, 30(8), 603-611.
Corbett A, Smith J, Ballard C (2013). New and emerging treatments for Alzheimer's disease (vol 12, pg 535, 2012).
EXPERT REVIEW OF NEUROTHERAPEUTICS,
13(7), 871-871.
Author URL.
Corbett A, Smith J, Ballard C (2013). New and emerging treatments for Alzheimer's disease (vol 12, pg 535, 2012).
EXPERT REVIEW OF NEUROTHERAPEUTICS,
13(6), 734-734.
Author URL.
Achterberg W, Pieper MJC, van Dalen-Kok AH, de Waal MWM, Husebo BS, Lautenbacher S, Kunz M, Scherder EJA, Corbett A (2013). Pain management in patients with dementia. Clinical Interventions in Aging, 1471-1471.
Ballard C, Corbett A (2013). Randomised controlled trial: a small proportion of people with dementia and neuropsychiatric symptoms experience clinically significant worsening when antidepressants are discontinued (Evidence-Based Medicine (2013) 18, (27-28)). Evidence-Based Medicine, 18(3).
Ballard C, Francis P, Corbett A (2013). Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies.
International Psychogeriatrics,
25(5), 687-689.
Abstract:
Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies
Behavioral and psychological symptoms of dementia (BPSD) frequently arise in people with Alzheimer's disease (AD) and other dementias. They cause significant distress and confer risk to the person and others, in addition to presenting a complex clinical challenge for treatment (Ballard et al. 2009b). There is good evidence for the value of first-line management strategies such as psychological interventions and treatment of concurrent medical conditions, particularly pain, which are known to be effective (Ballard et al. 2009b). However, there are limited pharmacological treatment options for severe aggression, which causes significant risk, and for other severe BPSD which do not respond to first-line approaches. The only pharmacological intervention with an adequate evidence base is the prescription of atypical antipsychotics, where 18 placebo-controlled trials have evaluated the effect of treatment over 6–12 weeks. The literature indicates modest but significant benefits in the treatment of aggression and psychosis with risperidone and aripiprazole (Cohen's d standardized effect size of 0.2), uncertain benefits with olanzapine, and no benefits with quetiapine (Ballard and Howard, 2006; Schneider et al. 2006a; Ballard et al. 2009b; Corbett et al. 2012). Unfortunately, the benefits of longer term prescribing are more limited (Schneider et al. 2006b; Ballard et al. 2008) and there have been increasing concerns regarding the potential for serious adverse outcomes, including accelerated cognitive decline, stroke, and death (Schneider et al. 2006b; Ballard et al. 2009a). There is therefore an urgent imperative to identify more effective pharmacological treatments for severe BPSD which have a better safety profile, particularly for long-term treatment and prophylaxis. Despite this urgency, there has been very little effort toward developing or evaluating potential novel therapies for the treatment of key symptoms such as aggression, psychosis, restlessness, and apathy.
Abstract.
Corbett A, Francis P, Ballard C (2013). Safety and efficacy of memantine extended-release in the management of alzheimer's disease.
Clinical Medicine Insights: Therapeutics,
5, 95-102.
Abstract:
Safety and efficacy of memantine extended-release in the management of alzheimer's disease
Alzheimer's disease (AD) affects the majority of the 35 million people with dementia worldwide. Four pharmacological treatment options are available for this patient group, of which memantine is licensed for treatment of people with moderate to severe stages of the condition. Memantine acts through its function as an NMDA-glutamate receptor blocker and has an established safety profile. The evidence supporting its efficacy in people with AD includes a number of large randomized clinical trials showing benefit to cognition, function, and overall clinical outcome. Additional favorable health economics analyses have confirmed the clinical and cost-effectiveness of this drug. More recently an extended-release formulation has been developed. This review outlines the key evidence base supporting memantine as a treatment for moderate to severe AD, in addition to discussing the conditions under which it may provide additional value in combination with other drugs. The review also discusses the use of memantine to address behavioral and psychological symptoms of dementia (BPSD) arising in people with AD and the limited evidence around its use in AD in people with Down's syndrome. Finally the review considers the potential value of the extended release formulation in AD. © the author(s), publisher and licensee Libertas Academica Ltd.
Abstract.
Ballard C, Corbett A (2012). A small proportion of people with dementia and neuropsychiatric symptoms experience clinically significant worsening when antidepressants are discontinued. Evidence Based Medicine, 18(1), 27-28.
Corbett A, Ballard C (2012). Antipsychotics and Mortality in Dementia. American Journal of Psychiatry, 169(1), 7-9.
Corbett A, Husebo B, Malcangio M, Staniland A, Cohen-Mansfield J, Aarsland D, Ballard C (2012). Assessment and treatment of pain in people with dementia.
Nature Reviews Neurology,
8(5), 264-274.
Abstract:
Assessment and treatment of pain in people with dementia
Many elderly people experience pain and regularly take analgesic medication. Pain is also frequent in people with dementia, particularly those with severe disease. As no robust clinical guidelines are available for the treatment of pain in the context of dementia, the risk of inadequate treatment in individuals with this condition is high. Furthermore, our understanding of the aetiology of pain and the potential role of dementia-associated neuropathology in pain is limited. These issues are important in the clinical management of individuals with dementia, as untreated pain is a major contributor to reduced quality of life and disability, and can lead to increased behavioural and psychological symptoms. Assessment scales to identify pain in people with dementia have been highlighted in recent studies, but there is little evidence for consistency between these tools. Numerous studies have evaluated various approaches for the treatment of pain, including stepped-care protocols and/or administration of paracetamol and opioid medications. In this Review, we summarize the best-available evidence regarding the aetiology, assessment and treatment of pain in people with dementia. Further validation of assessment tools and large-scale trials of treatment approaches in people with dementia are needed to improve clinical guidance for the treatment of pain in these individuals © 2012 Macmillan Publishers Limited. All rights reserved.
Abstract.
(2012). Correction: Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PloS one, 7(9).
Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, et al (2012). Drug repositioning for Alzheimer's disease. Nature Reviews Drug Discovery, 11(11), 833-846.
Hanney M, Prasher V, Williams N, Jones EL, Aarsland D, Corbett A, Lawrence D, Yu L-M, Tyrer S, Francis PT, et al (2012). Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.
LANCET,
379(9815), 528-536.
Author URL.
Corbett A, Ballard C (2012). New and emerging treatments for Alzheimer's disease.
Expert Opin Emerg Drugs,
17(2), 147-156.
Abstract:
New and emerging treatments for Alzheimer's disease.
INTRODUCTION: Alzheimer's disease and other dementias represent a significant and increasing clinical challenge. Dementia is also associated with a substantial economic cost and burden to health service provision. Existing treatments slow the progression of symptoms of the disease, but their efficacy does not extend to all patients and is not sustained beyond an average of 6 months. It is, therefore, critical to address the current lack of effective treatments to target the underlying pathology and disease process in Alzheimer's disease. AREAS COVERED: This review aims to highlight the main areas of new therapeutic development and discuss some of the main therapies currently being evaluated in clinical trials. Despite a number of promising rationales for therapeutic treatments in Alzheimer's disease, very few of these avenues have been developed beyond preclinical studies. The predominant focus of the current article is on treatments currently in Phase II and Phase III clinical trials, but some other promising areas of development are also discussed. There are currently only three therapeutics being investigated in Phase III clinical trials. This emphasizes the substantial caution and underinvestment in treatment development in this area. EXPERT OPINION: There is a distinct lack of novel approaches in the pipeline, and whether there is a new disease-modifying therapy for Alzheimer's disease in the next 5 years almost entirely depends on the success of currently ongoing immunotherapy studies. Importantly, there is potential benefit in exploring existing licensed treatments alongside novel drug development to increase the focus on novel targets within this time frame.
Abstract.
Author URL.
Ballard C, Corbett A (2012). New guidelines on disorders associated with dementia. Nature Reviews Neurology, 8(12), 663-664.
Ballard C, Jones E, Gauge N, Aarsland D, Nilsen OB, Saxby BK, Lowery D, Corbett A, Wesnes K, Katsaiti E, et al (2012). Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PLoS ONE, 7(6), e37410-e37410.
Corbett A, Smith J, Creese B, Ballard C (2012). Treatment of Behavioral and Psychological Symptoms of Alzheimer’s Disease. Current Treatment Options in Neurology, 14(2), 113-125.
Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011). Alzheimer's disease.
LANCET,
377(9770), 1019-1031.
Author URL.
Creese B, Ballard C, Corbett A, Aarsland D (2011). Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality. Expert Opinion on Drug Safety, 10, 35-43.
Ballard C, Corbett A, Jones EL (2011). Dementia: challenges and promising developments. The Lancet Neurology, 10(1), 7-9.
Ballard C, Corbett A, Pickett J (2011). Depression and dementia.
Ment Health Today, 23-25.
Author URL.
Talà A, Monaco C, Nagorska K, Exley RM, Corbett A, Zychlinsky A, Alifano P, Tang CM (2011). Glutamate utilization promotes meningococcal survival in vivo through avoidance of the neutrophil oxidative burst. Molecular Microbiology, 81(5), 1330-1342.
Corbett A, Ballard C (2011). Information provision services in dementia care. International Journal of Older People Nursing, 6(3), 217-226.
Ballard C, Khan Z, Clack H, Corbett A (2011). Nonpharmacological treatment of Alzheimer disease.
Can J Psychiatry,
56(10), 589-595.
Abstract:
Nonpharmacological treatment of Alzheimer disease.
OBJECTIVE: to review the key nonpharmacological treatment approaches to the cognitive and functional symptoms of Alzheimer disease (AD). METHODS: We searched and critically analyzed the most recent relevant literature pertaining to the nonpharmacological treatment of AD. RESULTS: There is evidence from a modest number of well-conducted randomized controlled trials (RCTs) that various nonpharmacological approaches, including cognitive training, cognitive rehabilitation, and cognitive stimulation therapy (CST), confer modest but significant benefits in the treatment of cognitive symptoms in people with AD, and that there may be additive benefits in combination with cholinesterase inhibitor therapy. Cognitive rehabilitation also appears to result in functional benefits in AD. The modest number of RCTs focusing on cognitive training in AD is consistent with the results of larger cognitive training trials in healthy older people. however, there is no convincing evidence of any benefits associated with brain training games. CONCLUSION: an emerging evidence base indicates that different approaches to cognitive training and cognitive stimulation in people with AD confer modest but significant benefits. The best evidence base is for CST, although this approach is labour-intensive, and requires further evaluation of cost-effectiveness. There is currently no evidence that brain training games provide any significant benefit to people with AD.
Abstract.
Author URL.
Corbett A, Stevens J, Aarsland D, Day S, Moniz-Cook E, Woods R, Brooker D, Ballard C (2011). Systematic review of services providing information and/or advice to people with dementia and/or their caregivers. International Journal of Geriatric Psychiatry, 27(6), 628-636.
Ballard C, Smith J, Husebo B, Aarsland D, Corbett A (2011). The role of pain treatment in managing the behavioural and psychological symptoms of dementia (BPSD).
Int J Palliat Nurs,
17(9), 420-424.
Author URL.
Ballard C, Kahn Z, Corbett A (2011). Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
Drugs Aging,
28(10), 769-777.
Abstract:
Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) account for 10-15% of late onset dementias. Key treatment targets include cognitive and functional impairments, neuropsychiatric symptoms including intense and persistent visual hallucinations, and parkinsonism. Six-month, placebo-controlled randomized controlled trials (RCTs) of the cholinesterase inhibitor rivastigmine have indicated modest but significant benefits in cognition, function, global outcome and neuropsychiatric symptoms in both PDD and DLB. The evidence base for other cholinesterase inhibitors from RCTs is inconclusive. More recent RCTs with memantine in PDD/DLB patients indicate a benefit with regard to global outcome, with some suggestion of a specific benefit with respect to sleep disturbance. Given the risk of severe antipsychotic sensitivity reactions, antipsychotics should be avoided. A significant proportion of PDD/DLB patients are responsive to levodopa, but care needs to be taken with anti-parkinsonian treatments because of their potential propensity to exacerbate neuropsychiatric symptoms, particularly hallucinations.
Abstract.
Author URL.
Ballard C, Corbett A (2010). Management of neuropsychiatric symptoms in people with dementia.
CNS Drugs,
24(9), 729-739.
Abstract:
Management of neuropsychiatric symptoms in people with dementia.
Neuropsychiatric symptoms are frequent and troublesome in people with dementia and present a major treatment challenge for clinicians. Most good practice guidelines suggest non-pharmacological treatments as the first-line therapy and there is emerging evidence, including randomized controlled trials, that a variety of psychological and training interventions, including social interaction and person-centred care training, are effective. There is evidence from meta-analyses that some atypical antipsychotic drugs, specifically risperidone and aripiprazole, confer benefit in the treatment of aggression in people with Alzheimer's disease over a period of up to 12 weeks. However, these benefits have to be considered in the context of significant adverse events, including extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In addition, the limited evidence available does not indicate ongoing treatment benefits over longer periods of therapy. The evidence is limited for other pharmacological treatment approaches, but the best evidence is probably for carbamazepine, memantine and citalopram. There is very limited evidence for any therapies in non-Alzheimer dementias. In conclusion, it is important in most situations to limit the use of antipsychotic medication to short-term treatment (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non-pharmacological therapies offer a viable and effective alternative in many situations. Adequately powered randomized controlled trials for the treatment of clinically significant agitation are urgently needed to explore alternative pharmacological therapies.
Abstract.
Author URL.
Ballard C, Corbett A, Chitramohan R, Aarsland D (2009). Management of agitation and aggression associated with Alzheimerʼs disease: controversies and possible solutions. Current Opinion in Psychiatry, 22(6), 532-540.
Carpenter EP, Corbett A, Thomson H, Adacha J, Jensen K, Bergeron J, Kasampalidis I, Exley R, Winterbotham M, Tang C, et al (2007). AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis. The EMBO Journal, 26(5), 1363-1372.
Corbett A, Exley R, Bourdoulous S, Tang CM (2004). Interactions between <i>Neisseria meningitidis</i> and human cells that promote colonisation and disease.
Expert Reviews in Molecular Medicine,
6(14), 1-14.
Abstract:
Interactions between Neisseria meningitidis and human cells that promote colonisation and disease
Neisseria meningitidis is the leading cause of bacterial meningitis, a potentially fatal condition that particularly affects children. Multiple steps are involved during the pathogenesis of infection, including the colonisation of healthy individuals and invasion of the bacterium into the cerebrospinal fluid. The bacterium is capable of adhering to, and entering into, a range of human cell types, which facilitates its ability to cause disease. This article summarises the molecular basis of host–pathogen interactions at the cellular level during meningococcal carriage and disease.
Abstract.
Chapters
Corbett A, Ballard C, Creese BA (2018). Evidence-based management of behavioural and psychological symptoms of dementia. In Michel J-P, Beattie BL, Martin FC, Walston JD (Eds.)
Oxford Textbook of Geriatric Medicine, Oxford University Press, 1015-1020.
Abstract:
Evidence-based management of behavioural and psychological symptoms of dementia
Abstract.
Ballard C, Corbett A (2012). Management of agitation and aggression: Controversies and possible solutions. In (Ed) Advances in Alzheimer's Disease Management, 69-79.
Conferences
Ballard C, Allan L, Corbett A, Creese B, Brooker H, Fox C, Sami S, Shepstone L, Khondoker M, Richardson K, et al (2019). Interaction of Biological and Psychosocial Factors in Dementia.
Author URL.
Drageset J, Eide GE, Corbett A (2017). Patterns of health-related quality of life among nursing home residents with and without cancer.
Author URL.
Dowding D, Lichtner V, Esterhuizen P, Closs SJ, Long A, Corbett A, Briggs M (2015). Pain Assessment Tools for Individuals with Dementia: a Metareview.
Author URL.
Ballard C, Mills R, Williams H, Corbett A, Cummings J (2014). TREATMENT OF PSYCHOSIS IN PARKINSON'S DISEASE AND PARKINSON'S DISEASE DEMENTIA.
Author URL.
Publications by year
In Press
Sabatini S, Martyr A, Ukoumunne OC, Ballard C, Collins R, Pentecost C, Rusted JM, Quinn C, Anstey KJ, Kim S, et al (In Press). Attitudes Toward Own Aging and Cognition among Individuals Living with and without Dementia: Findings from the IDEAL Programme and the PROTECT Study.
Abstract:
Attitudes Toward Own Aging and Cognition among Individuals Living with and without Dementia: Findings from the IDEAL Programme and the PROTECT Study
Abstract
. Background: it is unclear whether people with dementia (PwD) have more negative attitudes toward own aging (ATOA) than people without dementia and what factors influence ATOA among PwD. We investigated whether PwD have more negative ATOA than individuals without dementia and whether cognition and dementia subtype are associated with ATOA in PwD.Methods: Data from the IDEAL and PROTECT studies were used to compare ATOA between 1,502 PwD (mean (SD) age = 76.3 (8.5)) and 6,377 individuals without dementia (mean (SD) age = 66.1 (7.1)). Linear regressions and ANOVA were used.Results: PwD reported slightly more negative ATOA than people without dementia; this relationship disappeared after controlling for depression and self-rated health. In PwD more positive ATOA showed negligible associations with better general cognition, memory performance, verbal fluency, and visuospatial ability. However, after adjusting for covariates only better visuospatial ability predicted more positive ATOA. Additional analyses showed that before and after controlling for covariates, individuals with poorer self-reported visual acuity have more negative ATOA. Amongst dementia subtypes, people with Parkinson’s disease dementia and dementia with Lewy bodies reported most negative ATOA. Conclusions: ATOA between PwD and people without dementia do not differ. ATOA in PwD appear to be affected not by cognitive impairment but by other characteristics that vary across dementia subtypes. Among PwD, those with Parkinson’s disease dementia and dementia with Lewy bodies may have higher risk of experiencing negative ATOA due to the motor and visual impairments that they experience.
Abstract.
Sabatini S, Ukoumunne O, Ballard C, Collins R, Anstey K, Diehl M, Brothers A, Wahl H-W, Corbett A, Hampshire A, et al (In Press). Cross-Sectional Association between Objective Cognitive Performance and Perceived Age-related Gains and Losses in Cognition. International Psychogeriatrics
Sabatini S, Ukoumunne O, Brothers A, Diehl M, Wahl H-W, Ballard C, Collins R, Corbett A, Brooker H, Clare L, et al (In Press). Differences in Awareness of Positive and Negative Age-Related Changes Account for Variability in Health Outcomes.
Abstract:
Differences in Awareness of Positive and Negative Age-Related Changes Account for Variability in Health Outcomes
Abstract
. Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health. We used cross-sectional data from the PROTECT study (N= 6,192; mean(SD) age= 66.1(7.0)). Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-square tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4. Experiencing one’s ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
Abstract.
Sabatini S, Ukoumunne O, Brothers A, Diehl M, Wahl H-W, Clive B, Collins R, Corbett A, Brooker H, Clare L, et al (In Press). Differences in awareness of positive and negative age-related changes account for variability in health outcomes.
European Journal of AgeingAbstract:
Differences in awareness of positive and negative age-related changes account for variability in health outcomes
Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health.
We used cross-sectional data from the PROTECT study (N= 6,192; mean (SD) age= 66.1(7.0)).
Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-squared tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4.
Experiencing one’s ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
Abstract.
Ballard C, Brooker H, Corbett A, Ismail Z, Creese B, Wesnes K (In Press). FLAME: a computerized neuropsychological composite for trials in early dementia. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Creese B, Brooker H, Aarsland D, Corbett A, Ballard C, Ismail Z (In Press). Genetic risk for Alzheimer disease, cognition and Mild Behavioral Impairment in healthy older adults.
Abstract:
Genetic risk for Alzheimer disease, cognition and Mild Behavioral Impairment in healthy older adults
BACKGROUND: Mild Behavioral Impairment (MBI) is a neuropsychiatric syndrome describing later-life emergent apathy, mood/anxiety symptoms, impulse dyscontrol, social inappropriateness and psychosis that are not attributable to psychiatric diagnoses. MBI is an at-risk state for incident cognitive decline and dementia, and is associated with dementia biomarkers including amyloid beta; and neurofilament light. Thus, MBI may be an early clinical marker of neurodegenerative disease. In this study, we hypothesized that stratification by MBI in a cognitively normal sample would moderate the signal between Alzheimer disease (AD) genetic risk and cognition.
METHODS: Genetic, cognitive and MBI data was available for 3,126 PROTECT study participants over 50 without dementia. A general cognitive composite score was constructed based on scores on paired associates learning, digit span, self-ordered search and verbal reasoning. MBI was assessed using the MBI Checklist. Polygenic scores for AD were split by tertile (representing low, medium and high risk) and the sample was stratified by MBI into those with no symptoms and those with any symptoms.
RESULTS: AD genetic risk was associated with poorer cognition in the MBI strata only (MBI: F(2,1746)=4.95, p=0.007; no MBI: F(2,1366)=0.72, p=0.49). The mean difference between low and high genetic risk groups was significant (p=0.005) and the standardised effect size in the MBI sample was higher than in the whole sample.
CONCLUSIONS: These findings justify MBI screening to enrich samples with at-risk individuals, and underscore the importance of late-life neuropsychiatric symptoms in cognitive ageing.
Abstract.
Creese B, Arathimos R, Brooker H, Aarsland D, Corbett A, Lewis C, Ballard C, Ismail Z (In Press). Genetic risk for Alzheimer’s disease, cognition and Mild Behavioral Impairment in healthy older adults. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Clare L, Kudlicka A, Oyebode JR, Jones RW, Bayer A, Leroi I, Kopelman M, James IA, Culverwell A, Pool J, et al (In Press). Goal-oriented cognitive Rehabilitation in Early-stage Alzheimer’s and related dementias: a multi-centre single-blind randomised controlled Trial (GREAT). Health Technology Assessment
Ballard C, Creese B, Gatt A, Doherty P, Francis PT, Whitfield D, Corbett A, Corcoran J, Hanger D, Thuret S, et al (In Press). Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease.
Abstract:
Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease
AbstractThe current paper describes the identification of novel candidate compounds for repositioning as treatments for Alzheimer’s disease (AD) from the CMAP library. Candidate compounds were identified based on inverse correlation with transcriptome signatures developed from meta-analyses of Alzheimer RNA expression studies using the SPIED platform. The 78 compounds with a significant inverse correlation were taken forward into an in vitro programme using 6 well validated screening assays relevant to potential treatment targets in AD. Nineteen pf the compounds were hits in at least 2 of these assays. A description of each of these compounds is presented.
Abstract.
sabatini S, Ukoumunne OC, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (In Press). International relevance of Two Measures of Awareness of Age-Related Change (AARC).
Abstract:
International relevance of Two Measures of Awareness of Age-Related Change (AARC)
Abstract
. Background: a questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over. Methods: Data from 9,410 participants (Mean (SD) age= 65.9 (7.1)) in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across men and women, individuals with and without a university degree, and in middle age, early old age, and advanced old age; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We explored the relationship between demographic variables (age, sex, marital status, employment, and university education) and AARC. Results: We confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability and good convergent validity for AARC losses, but weak convergent validity for AARC gains. For both scales metric invariance was held for the two subgroups defined by education level and age. For the AARC-50 subscale, but not for the AARC-10 SF, strong invariance was also held for the two subgroups defined by sex. Age, sex, marital status, employment, and university education predicted AARC gains and losses. Conclusions: the AARC-10 SF and AARC-50 cognitive functioning subscale identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
Abstract.
Arathimos R, Fabbri C, Vassos E, Davis KAS, Pain O, Gillett A, Coleman JRI, Hanscombe K, Hagenaars S, Jermy B, et al (In Press). Latent subtypes of manic or irritable episode symptoms in two population-based cohorts.
Abstract:
Latent subtypes of manic or irritable episode symptoms in two population-based cohorts
AbstractBackgroundEpisodic changes in mood characterise disorders such as bipolar disorder, which includes distinct periods of manic excitability or irritability, along with additional symptoms experienced during these periods. Common clinical understanding informs diagnostic criteria and epidemiological studies reflect clinical thresholds.AimsTo use a data-driven approach to defining groupings of symptoms experienced during periods of manic or irritable mood, which could inform understanding of mood disorders and guide case classification by identifying subgroups with homogeneous clinical/functional outcomes.MethodsWe used latent class analysis (LCA) to conduct an exploration of the latent structure in symptom responses in the UK Biobank and PROTECT studies, by investigating how symptoms, experienced during periods of manic or irritable mood, formed latent subgroups. We tested associations of latent subgroups with sociodemographic characteristics, diagnoses of psychiatric disorders and polygenic risk scores (PRS).ResultsFive latent classes were identified that captured patterns of symptoms experienced during periods of manic or irritable mood (N=42,183) in UK Biobank. We identified one class that experienced disruptive episodes of mostly irritable mood that was largely comprised of cases of depression/anxiety, and a class of individuals with increased confidence/creativity that reported lower disruptiveness and lower functional impairment. The five latent classes were replicated in an independent cohort, the PROTECT study (N=4,445), with similar distinctions between classes.ConclusionOur data-driven approach to grouping individuals identified distinct latent classes. A dimensional classification of mood disorders informed by our findings will be able to better assess or subtype these disorders in future studies.
Abstract.
Creese B, Khan Z, Henley W, O’Dwyer S, Corbett A, Da Silva MV, Mills K, Wright N, Testad I, Aarsland D, et al (In Press). Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety between 2015 and 2020.
Abstract:
Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety between 2015 and 2020
BackgroundLoneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies and are potentially modifiable.MethodWe analysed mental health data collected during COVID-19 from adults aged 50 and over alongside comparable annual data collected between 2015 and 2019 from the same sample. Trajectories of depression (PHQ-9) and anxiety (GAD-7) were analysed with respect to loneliness, physical activity levels and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression.Results3,281 people completed the COVID-19 mental health questionnaire, all had at least one data point prior to 2020. In 2020, the adjusted PHQ-9 score for loneliness was 3.2. (95% CI: 3.0-3.4), an increase of one point on previous years and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.2, 95% CI: 1.1-1.3). PHQ-9 was 2.6 (95% CI: 2.4-2.8) in people with decreased physical activity, an increase of 0.5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.7 (95% CI: 1.6-1.8), similar to previous years. A similar relationship was observed for GAD-7 though the differences were smaller and the absolute burden of symptoms lower.ConclusionsAfter accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors.
Abstract.
Creese B, Khan Z, Henley W, O'Dwyer S, Corbett A, Vasconcelos Da Silva M, Mills K, Wright N, Testad I, Aarsland D, et al (In Press). Loneliness, physical activity and mental health during Covid-19: a longitudinal analysis of depression and anxiety in adults over 50 between 2015 and 2020. International Psychogeriatrics
Creese BA, Brooker H, Ismail Z, Wesnes K, Adam H, Khan Z, Maria M, Corbett A, Aarsland D, Ballard C, et al (In Press). Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults. American Journal of Geriatric Psychiatry
Rao R, Creese B, Aarsland D, Kalafatis C, Khan Z, Corbett A, Ballard C (In Press). Risky drinking and cognitive impairment in community residents. aged 50 and over. Aging and Mental Health
Wolfova K, Creese B, Aarsland D, Ismail Z, Corbett A, Ballard C, Hampshire A, Cermakova P (In Press). Sex differences in the association of mild behavioral impairment with cognitive aging.
Abstract:
Sex differences in the association of mild behavioral impairment with cognitive aging
ABSTRACTINTRODUCTIONWe aimed to explore sex differences in the association of mild behavioral impairment (MBI) with the level of cognitive performance and its rate of decline in a cohort of people without dementia with the longest term follow up of cognition.METHODSWe studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models.RESULTSMales exhibited more often symptoms of decreased motivation, impulse dyscontrol and social inappropriateness, while less often symptoms of emotional dysregulation. The associations of MBI domains with some measures of cognitive performance and decline was stronger in males than females, with the exception of emotional dysregulation.DISCUSSIONMBI may influence cognition to a greater extent in males than in females.
Abstract.
Allan L, Corbett A, Valderas Martinez J (In Press). Social prescribing programmes to prevent or delay frailty in community-dwelling older adults. Geriatrics
Sabatini S, Ukoumunne O, Ballard C, Collins R, Corbett A, Brooker H, Clare L (In Press). The Cross-sectional Relationship between Pain and Awareness of Age-Related Changes. British Journal of Pain
Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, et al (In Press). The Dementias Platform UK (DPUK) Data Portal.
Abstract:
The Dementias Platform UK (DPUK) Data Portal
AbstractThe Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data.The Data Portal uses UK Secure eResearch Platform (UKSeRP) infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication.Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Project are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Abstract.
Stewart G, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Brooker H, Charlton R, Happe F (In Press). The cognitive profile of middle-aged and older adults with high vs. low autistic traits. Autism Research
Creese B, Corbett A, Ballard C (In Press). The mental and physical health of older adults with a genetic predisposition for autism. Autism Research: official journal of the International Society for Autism Research
sabatini S, Ukoumunne O, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (In Press). UK Validation of Two Measures of Awareness of Age-Related Change (AARC).
Abstract:
UK Validation of Two Measures of Awareness of Age-Related Change (AARC)
Abstract
. Background: a questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over. Methods: Data from 14,797 participants in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across males and females and across individuals with and without a university degree; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We also explored the relationship between demographic variables and AARC. Results: We confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability and convergent validity. The meaning of AARC gains and losses was the same across males and females and across individuals with and without a university degree. Items composing AARC scales had the same meaning across individuals with and without a university degree. Items composing the AARC-50 cognitive functioning subscale had the same meaning across males and females. Two items in the AARC-10 SF had different meaning across males and females. Demographic variables significantly predicted AARC gains and losses. Conclusions: the AARC-10 SF and AARC-50 cognitive functioning subscale can help to identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
Abstract.
2023
O'Nions E, Petersen I, Buckman JEJ, Charlton R, Cooper C, Corbett A, Happé F, Manthorpe J, Richards M, Saunders R, et al (2023). Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data. The Lancet Regional Health - Europe, 29, 100626-100626.
McDermid J, Ballard C, Khan Z, Aarsland D, Fox C, Fossey J, Clare L, Moniz-Cook E, Soto-Martin M, Sweetnam A, et al (2023). Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.
Int J Geriatr Psychiatry,
38(1).
Abstract:
Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.
OBJECTIVES: This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS: This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS: Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p
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Author URL.
Sabatini S, Dritschel B, Rupprecht FS, Ukoumunne OC, Ballard C, Brooker H, Corbett A, Clare L (2023). Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.
Aging Ment Health, 1-9.
Abstract:
Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.
OBJECTIVE: Lower awareness of age-related gains (AARC-gains) and higher awareness of age-related losses (AARC-losses) may be risk factors for depressive and anxiety symptoms. We explored whether: (1) Baseline AARC-gains and AARC-losses predict depressive and anxiety symptoms at one-year follow-up; (2) age and rumination moderate these associations; (3) levels of AARC-gains and AARC-losses differ among individuals with different combinations of current and past depression and/or with different combinations of current and past anxiety. METHODS: in this one-year longitudinal cohort study participants (N = 3386; mean age = 66.0; SD = 6.93) completed measures of AARC-gains, AARC-losses, rumination, depression, anxiety, and lifetime diagnosis of depression and anxiety in 2019 and 2020. Regression models with tests of interaction were used. RESULTS: Higher AARC-losses, but not lower AARC-gains, predicted more depressive and anxiety symptoms. Age did not moderate these associations. Associations of lower AARC-gains and higher AARC-losses with more depressive symptoms and of higher AARC-losses with more anxiety symptoms were stronger in those with higher rumination. Individuals with both current and past depression reported highest AARC-losses and lowest AARC-gains. Those with current, but not past anxiety, reported highest AARC-losses. CONCLUSION: Perceiving many age-related losses may place individuals at risk of depressive and anxiety symptoms, especially those who frequently ruminate.
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2022
Sabatini S, Ukoumunne OC, Brothers A, Diehl M, Wahl H-W, Ballard C, Collins R, Corbett A, Brooker H, Clare L, et al (2022). Differences in awareness of positive and negative age-related changes accounting for variability in health outcomes.
Eur J Ageing,
19(4), 1087-1097.
Abstract:
Differences in awareness of positive and negative age-related changes accounting for variability in health outcomes.
Higher awareness of positive age-related changes (AARC gains) is related to better mental health, whereas higher awareness of negative age-related changes (AARC losses) is related to poorer mental and physical health. So far perceived gains and losses have been explored separately, but people report gains and losses concurrently in varying degrees, and different profiles of gains and losses may be differentially associated with health. We identified profiles of gains and losses and explored whether different profiles differed in physical, mental, and cognitive health. We used cross-sectional data from the PROTECT study (N = 6192; mean (SD) age = 66.1 (7.0)). Using latent profile analysis, a four-class solution showed the best model fit. We found that 45% of people perceived many gains and few losses (Class 1); 24% perceived moderate gains and few losses (Class 2); 24% perceived many gains and moderate losses (Class 3); 7% perceived many gains and many losses (Class 4). Analysis of variance and Chi-squared tests showed that Class 1 had relatively better physical, mental, and cognitive health, followed by Classes 2, 3, and 4. Experiencing one's ageing to a high degree as gain may be related to better health only when individuals interpret ageing as involving low levels of loss across several life domains. Risk in terms of poorer health emerged in those who perceived high losses. Considering gains and losses in parallel, rather than separately, may lead to a more fine-tuned understanding of relations with health.
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Author URL.
Sabatini S, Ukoumunne OC, Ballard C, Collins R, Corbett A, Brooker H, Clare L (2022). Exploring awareness of age-related changes among over 50s in the UK: findings from the PROTECT study.
Int Psychogeriatr,
34(9), 789-803.
Abstract:
Exploring awareness of age-related changes among over 50s in the UK: findings from the PROTECT study.
OBJECTIVES: Older people describe positive and negative age-related changes, but we do not know much about what contributes to make them aware of these changes. We used content analysis to categorize participants' written comments and explored the extent to which the identified categories mapped onto theoretical conceptualizations of influences on awareness of age-related change (AARC). DESIGN: Cross-sectional observational study. PARTICIPANTS: the study sample comprised 609 UK individuals aged 50 years or over (mean (SD) age = 67.9 (7.6) years), enrolled in the PROTECT study. MEASUREMENTS: Between January and March 2019, participants provided demographic information, completed a questionnaire assessing awareness of age-related change (AARC-10 SF), and responded to an open-ended question asking them to comment on their responses. RESULTS: While some of the emerging categories were in line with the existing conceptual framework of AARC (e.g. experiencing negative changes and attitudes toward aging), others were novel (e.g. engagement in purposeful activities or in activities that distract from age-related thoughts). Analysis revealed some of the thought processes involved in selecting responses to the questionnaire items, demonstrating different ways in which people make sense of specific items. CONCLUSIONS: Results support the ability of the AARC questionnaire to capture perceived age-related changes in cognitive functioning, physical and mental health, and engagement in social activities and in healthy and adaptive behaviors. However, findings also suggest ways of enriching the theoretical conceptualization of how AARC develops and offer insights into interpretation of responses to measures of AARC.
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Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2022). Traumatic life experiences and post‐traumatic stress symptoms in middle‐aged and older adults with and without autistic traits. International Journal of Geriatric Psychiatry, 37(2).
2021
Wilson KE, Corbett A, Van Horn A, Guevara Beltran D, Ayers JD, Alcock J, Aktipis A (2021). Associations Between Change over Time in Pandemic-Related Stress and Change in Physical Activity.
J Phys Act Health,
18(11), 1419-1426.
Abstract:
Associations Between Change over Time in Pandemic-Related Stress and Change in Physical Activity.
BACKGROUND: Physical activity (PA) mitigated psychological distress during the initial weeks of the COVID-19 pandemic, yet not much is known about whether PA had effects on stress in subsequent months. We examined the relationship between change over time in COVID-related stress and self-reported change in PA between March and July 2020. METHODS: Latent growth modeling was used to examine trajectories of change in pandemic-related stress and test their association with self-reported changes in PA in an international sample (n = 679). RESULTS: the participants reported a reduction in pandemic-related stress between April and July of 2020. Significant linear (factor mean = -0.22) and quadratic (factor mean = 0.02) changes (Ps <. 001) were observed, indicating a deceleration in stress reduction over time. Linear change was related to change in PA such that individuals who became less active during the pandemic reported less stress reduction over time compared with those who maintained or increased their PA during the pandemic. CONCLUSIONS: Individuals who experienced the greatest reduction in stress over time during the pandemic were those who maintained their activity levels or became more active. Our study cannot establish a causal relationship between these variables, but the findings are consistent with other work showing that PA reduces stress.
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Author URL.
Sabatini S, Ukoumunne O, Ballard C, Collins R, Corbett A, Brooker H, Clare L (2021). Cross-sectional and longitudinal associations between subjective sleep difficulties and self-perceptions of aging. Behavioral Sleep Medicine
Ritchie S, Lawrence V, Jones J, Corbett A (2021). Engaging older adults in an online physical activity programme to improve cognition: a qualitative study. International Journal of Geriatric Psychiatry, 36(12), 1942-1949.
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2021). Predictors of activities of daily living in heathy older adults: Who benefits most from online cognitive training?.
Brain Behav,
11(11).
Abstract:
Predictors of activities of daily living in heathy older adults: Who benefits most from online cognitive training?
OBJECTIVES: to investigate the course of activities of daily living (IADL) functioning and possible predictors of performance changes in healthy older adults conducting either a General Cognitive Training (GCT) or a Reasoning Cognitive Training (ReaCT) or no training (control group, CG) over a period of 6 weeks, 3 months, and 6 months. SETTING AND PARTICIPANTS: an online, home-based GCT and ReaCT including n = 2913 healthy participants (GCT: n = 1096; ReaCT: n = 1022; CG: n = 794) aged 60 years and older. METHODS: Multilevel analysis were calculated to explore the nature of our outcome variables of IADL part a (independence) and part B (difficulty of tasks), and to detect possible predictors for participants' performance on IADL after CT. RESULTS: the random slopes models fitted better for the outcomes IADL Part B in the GCT group (χ2 (2) = 18.78, p
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Author URL.
Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2021). The Mental and Physical Health Profiles of Older Adults Who Endorse Elevated Autistic Traits.
J Gerontol B Psychol Sci Soc Sci,
76(9), 1726-1737.
Abstract:
The Mental and Physical Health Profiles of Older Adults Who Endorse Elevated Autistic Traits.
OBJECTIVES: the mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits and in older age. METHODS: a total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent sociocommunicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the "Autism Spectrum Trait" (AST) group. An age- and gender-matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the "Control Older Adults" (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. RESULTS: the AST group reported significantly elevated rates of psychiatric diagnoses compared to the COA group. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than the COA group. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. DISCUSSION: These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between the propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care.
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Author URL.
Sabatini S, Ukoumunne OC, Ballard C, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, Brooker H, Clare L, et al (2021). What does feeling younger or older than one’s chronological age mean to men and women? Qualitative and quantitative findings from the PROTECT study. Psychology & Health, 38(3), 324-347.
2020
Ballard C, Corbett A, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Wiliams G, Doherty P, et al (2020). Drug repositioning and repurposing. for Alzheimer disease. Nature Reviews Neurology
Ballard C, Orrell M, Moniz-Cook E, Woods R, Whitaker R, Corbett A, Aarsland D, Murray J, Lawrence V, Testad I, et al (2020). Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs.
Programme Grants for Applied Research,
8(6), 1-98.
Abstract:
Improving mental health and reducing antipsychotic use in people with dementia in care homes: the WHELD research programme including two RCTs
. Background
. The effective management of agitation and other neuropsychiatric and behavioural symptoms in people with dementia is a major challenge, particularly in care home settings, where dementia severity is higher and there is limited training and support for care staff. There is evidence for the value of staff training and the use of psychosocial approaches; however, no intervention currently exists that combines these elements into an intervention that is fit for purpose and effective in these settings based on evidence from a randomised controlled trial.
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. Objective
. The objective was to develop and evaluate a complex intervention to improve well-being, reduce antipsychotic use and improve quality of life in people with dementia in care homes through person-centred care, management of agitation and non-drug approaches.
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. Design
. This was a 5-year programme that consisted of six work packages. Work package 1 consisted of two systematic reviews of personalised psychosocial interventions for behavioural and psychological symptoms for people with dementia in care homes. Work package 2 consisted of a metasynthesis of studies examining implementation of psychosocial interventions, in addition to developing a draft Well-being and Health for people with Dementia (WHELD) programme. Work package 3 consisted of a factorial study of elements of the draft WHELD programme in 16 care homes. Work package 4 involved optimisation of the WHELD programme based on work package 3 data. Work package 5 involved a multicentre randomised controlled trial in 69 care homes, which evaluated the impact of the optimised WHELD programme on quality of life, agitation and overall neuropsychiatric symptoms in people with dementia. Work package 6 focused on dissemination of the programme.
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. Setting
. This programme was carried out in care homes in the UK.
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. Participants
. Participants of this programme were people with dementia living in care homes, and the health and care professionals providing treatment and care in these settings.
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. Results
. Work package 1: reviews identified randomised controlled trials and qualitative evidence supporting the use of psychosocial approaches to manage behavioural symptoms, but highlighted a concerning lack of evidence-based training manuals in current use. Work package 2: the meta-analysis identified key issues in promoting the use of interventions in care homes. The WHELD programme was developed through adaptation of published approaches. Work package 3: the factorial trial showed that antipsychotic review alone significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval 0.05 to 0.60). Antipsychotic review plus social interaction significantly reduced mortality (odds ratio 0.36, 95% confidence interval 0.23 to 0.57), but this group showed significantly worse outcomes in behavioural and psychological symptoms of dementia than the group receiving neither antipsychotic review nor social interaction (mean difference 7.37 symptoms, 95% confidence interval 1.53 to 13.22 symptoms). This detrimental impact was reduced when combined with social interaction (mean difference –0.44 points, 95% confidence interval –4.39 to 3.52 points), but with no significant benefits for agitation. The exercise intervention significantly improved neuropsychiatric symptoms (mean difference –3.58 symptoms, 95% confidence interval –7.08 to –0.09 symptoms) but not depression (mean difference –1.21 points, 95% confidence interval –4.35 to 1.93 points). Qualitative work with care staff provided additional insights into the acceptability and feasibility of the intervention. Work package 4: optimisation of the WHELD programme led to a final version that combined person-centred care training with social interaction and pleasant activities. The intervention was adapted for delivery through a ‘champion’ model. Work package 5: a large-scale, multicentre randomised controlled trial in 69 care homes showed significant benefit to quality of life, agitation and overall neuropsychiatric symptoms, at reduced overall cost compared with treatment as usual. The intervention conferred a statistically significant improvement in quality of life (Dementia Quality of Life Scale – Proxy z-score of 2.82, mean difference 2.54, standard error of measurement 0.88, 95% confidence interval 0.81 to 4.28, Cohen’s d effect size of 0.24; p = 0.0042). There were also statistically significant benefits in agitation (Cohen-Mansfield Agitation Inventory z-score of 2.68, mean difference –4.27, standard error of measurement 1.59, 95% confidence interval –7.39 to –1.15, Cohen’s d effect size of 0.23; p = 0.0076) and overall neuropsychiatric symptoms (Neuropsychiatric Inventory – Nursing Home version z-score of 3.52, mean difference –4.55, standard error of measurement 1.28, 95% confidence interval –7.07 to –2.02, Cohen’s d of 0.30; p < 0.001). The WHELD programme contributed to significantly lower health and social care costs than treatment as usual (cost difference –£4740, 95% confidence interval –£6129 to –£3156). Focus groups were conducted with 47 staff up to 12 months after the end of work package 5, which demonstrated sustained benefits. Work package 6: the outputs of the programme were translated into general practitioner workshops and a British Medical Journal e-learning module, an updated national best practice guideline and a portfolio of lay and care home outreach activities.
.
.
. Limitations
. Residents with dementia were not involved in the qualitative work.
.
.
. Conclusions
. The WHELD programme is effective in improving quality of life and reducing both agitation and overall neuropsychiatric symptoms in people with dementia in care homes. It provides a structured training and support intervention for care staff, with lower overall costs for resident care than treatment as usual.
.
.
. Future work
. It will be important to consider the long-term sustainability of the WHELD programme and cost-effective means of long-term implementation.
.
.
. Trial registration
. Current Controlled Trials ISRCTN40313497 and ISRCTN62237498.
.
.
. Funding
. This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 6. See the NIHR Journals Library website for further project information.
.
Abstract.
Sabatini S, Ukoumunne O, Ballard C, Brothers A, Kaspar R, Collins R, Kim S, Corbett A, Aarsland D, Hampshire A, et al (2020). International relevance of Two Measures of Awareness of Age-Related Change (AARC). BMC Geriatrics, 20
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2020). Lower cognitive baseline scores predict cognitive training success after 6 months in healthy older adults: Results of an online. <scp>RCT</scp>. International Journal of Geriatric Psychiatry, 35(9), 1000-1008.
Roheger M, Kalbe E, Corbett A, Brooker H, Ballard C (2020). Predictors of changes after reasoning training in healthy adults. Brain and Behavior, 10(12).
Ballard C, Corbett A (2020). Reducing psychotropic drug use in people with dementia living in nursing homes. International Psychogeriatrics, 32(3), 291-294.
Creese B, Brooker H, Aarsland D, Corbett A, Ballard C, Ismail Z (2020). Relationship between genetic risk for Alzheimer's, cognition and neuropsychiatric symptoms: a case study of DNA sampling and analysis through digital platform cohort studies. Alzheimer's & Dementia, 16(S10).
Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2020). Sleep problems and mental health difficulties in older adults who endorse high autistic traits.
Research in Autism Spectrum Disorders,
77Abstract:
Sleep problems and mental health difficulties in older adults who endorse high autistic traits
Background: Sleep problems and mental health difficulties are common in autistic children and young adults. However, these problems have seldom been studied in older autistic adults, or in older adults with elevated autistic traits. Method: Cross-sectional data was examined from 13,897 adults aged 50–81 years taking part in the PROTECT study, who reported whether they experienced persistent socio-communicative autistic traits. Approximately 1%, 187 individuals, were identified as endorsing high autistic traits in childhood and currently, henceforth ‘Autism Spectrum Trait’ (AST) group. An age- and gender-matched comparison group was formed of 6740 individuals who endorsed no autistic traits, henceforth ‘Control Older Adults’ (COA) group. Differences between AST and COA groups were explored in self-reported sleep behaviors, and in depression and anxiety symptoms. Results: AST and COA groups reported similar sleep duration and depth, and nighttime waking frequency. However, the AST group reported significantly more problems with falling asleep, morning drowsiness, and lower sleep quality/satisfaction than COA. More AST adults reported sleep problems past cut-off, as well as clinical levels of depression and anxiety, compared to COA. Adults in both groups who met criteria for high sleep problems experienced more mental health difficulties than those with few sleep problems. However, even amongst those without depression/anxiety, the AST group reported more sleep problems than the COA. Conclusions: These associations suggest that older adults with high autistic traits, like diagnosed autistic children/young adults, may experience poorer sleep and more mental health difficulties than those with low autistic traits. Further work is needed to see whether these results extend to older individuals meeting diagnostic criteria for autism.
Abstract.
Robinson L, Poole M, McLellan E, Lee R, Amador S, Bhattarai N, Bryant A, Coe D, Corbett A, Exley C, et al (2020). Supporting good quality, community-based end-of-life care for people living with dementia: the SEED research programme including feasibility RCT.
Programme Grants for Applied Research,
8(8), 1-254.
Abstract:
Supporting good quality, community-based end-of-life care for people living with dementia: the SEED research programme including feasibility RCT
BackgroundIn the UK, most people with dementia die in the community and they often receive poorer end-of-life care than people with cancer.ObjectiveThe overall aim of this programme was to support professionals to deliver good-quality, community-based care towards, and at, the end of life for people living with dementia and their families.DesignThe Supporting Excellence in End-of-life care in Dementia (SEED) programme comprised six interlinked workstreams. Workstream 1 examined existing guidance and outcome measures using systematic reviews, identified good practice through a national e-survey and explored outcomes of end-of-life care valued by people with dementia and family carers (n = 57) using a Q-sort study. Workstream 2 explored good-quality end-of-life care in dementia from the perspectives of a range of stakeholders using qualitative methods (119 interviews, 12 focus groups and 256 observation hours). Using data from workstreams 1 and 2, workstream 3 used co-design methods with key stakeholders to develop the SEED intervention. Worksteam 4 was a pilot study of the SEED intervention with an embedded process evaluation. Using a cluster design, we assessed the feasibility and acceptability of recruitment and retention, outcome measures and our intervention. Four general practices were recruited in North East England: two were allocated to the intervention and two provided usual care. Patient recruitment was via general practitioner dementia registers. Outcome data were collected at baseline, 4, 8 and 12 months. Workstream 5 involved economic modelling studies that assessed the potential value of the SEED intervention using a contingent valuation survey of the general public (n = 1002). These data informed an economic decision model to explore how the SEED intervention might influence care. Results of the model were presented in terms of the costs and consequences (e.g. hospitalisations) and, using the contingent valuation data, a cost–benefit analysis. Workstream 6 examined commissioning of end-of-life care in dementia through a narrative review of policy and practice literature, combined with indepth interviews with a national sample of service commissioners (n = 20).SettingThe workstream 1 survey and workstream 2 included services throughout England. The workstream 1 Q-sort study and workstream 4 pilot trial took place in North East England. For workstream 4, four general practices were recruited; two received the intervention and two provided usual care.ResultsCurrently, dementia care and end-of-life care are commissioned separately, with commissioners receiving little formal guidance and training. Examples of good practice rely on non-recurrent funding and leadership from an interested clinician. Seven key components are required for good end-of-life care in dementia: timely planning discussions, recognising end of life and providing supportive care, co-ordinating care, effective working with primary care, managing hospitalisation, continuing care after death, and valuing staff and ongoing learning. Using co-design methods and the theory of change, the seven components were operationalised as a primary care-based, dementia nurse specialist intervention, with a care resource kit to help the dementia nurse specialist improve the knowledge of family and professional carers. The SEED intervention proved feasible and acceptable to all stakeholders, and being located in the general practice was considered beneficial. None of the outcome measures was suitable as the primary outcome for a future trial. The contingent valuation showed that the SEED intervention was valued, with a wider package of care valued more than selected features in isolation. The SEED intervention is unlikely to reduce costs, but this may be offset by the value placed on the SEED intervention by the general public.LimitationsThe biggest challenge to the successful delivery and completion of this research programme was translating the ‘theoretical’ complex intervention into practice in an ever-changing policy and service landscape at national and local levels. A major limitation for a future trial is the lack of a valid and relevant primary outcome measure to evaluate the effectiveness of a complex intervention that influences outcomes for both individuals and systems.ConclusionsAlthough the dementia nurse specialist intervention was acceptable, feasible and integrated well with existing care, it is unlikely to reduce costs of care; however, it was highly valued by all stakeholders (professionals, people with dementia and their families) and has the potential to influence outcomes at both an individual and a systems level.Future workThere is no plan to progress to a full randomised controlled trial of the SEED intervention in its current form. In view of new National Institute for Health and Care Excellence dementia guidance, which now recommends a care co-ordinator for all people with dementia, the feasibility of providing the SEED intervention throughout the illness trajectory should be explored. Appropriate outcome measures to evaluate the effectiveness of such a complex intervention are needed urgently.Trial registrationCurrent Controlled Trials ISRCTN21390601.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 8, No. 8. See the NIHR Journals Library website for further project information.
Abstract.
Desai R, Charlesworth GM, Brooker HJ, Potts HWW, Corbett A, Aarsland D, Ballard CG (2020). Temporal Relationship Between Depressive Symptoms and Cognition in Mid and Late Life: a Longitudinal Cohort Study.
Journal of the American Medical Directors Association,
21(8), 1108-1113.
Abstract:
Temporal Relationship Between Depressive Symptoms and Cognition in Mid and Late Life: a Longitudinal Cohort Study
Objectives: to examine the bidirectional temporal relationship between depressive symptoms and cognition in relation to risk, reaction, and prodrome. Design: Cross-lag analysis of longitudinal data collected online at baseline and 12-month follow-up. Setting and Participants: a United Kingdom population cohort of 11,855 participants aged 50 years and over. Measures: Patient Health Questionnaire-9 (depressive symptoms), cognitive measures: Paired Associate Learning, Verbal Reasoning, Spatial Working Memory, and Digit Span. Results: Depressive symptoms predicted a decline in paired associates learning [β = −.020, P =. 013, (95% confidence interval [CI], ‒.036, −.004)] and verbal reasoning [β = −.014, P =. 016, (95% CI ‒.025, −.003)] but not vice versa. Depressive symptoms predicted [β = −.043, P <. 001, (95% CI ‒.060, −.026); β = −.029, P <. 001, (95% CI ‒.043, −.015)] and were predicted by [β = −.030, P = <. 001, (95% CI ‒.047, −.014); β = −.025, P =. 003, (95% CI ‒.041, −.009)], a decline in spatial working memory and verbal digit span, respectively. Conclusions and Implications: Depressive symptoms may be either a risk factor or prodrome for cognitive decline. In addition, a decline in attention predicts depressive symptoms. Clinical implications and implications for further research are discussed.
Abstract.
Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, et al (2020). The Dementias Platform UK (DPUK) Data Portal.
Eur J Epidemiol,
35(6), 601-611.
Abstract:
The Dementias Platform UK (DPUK) Data Portal.
The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Abstract.
Author URL.
2019
Brooker H, Wesnes KA, Ballard C, Hampshire A, Aarsland D, Khan Z, Stenton R, McCambridge L, Corbett A (2019). An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults.
Int J Geriatr Psychiatry,
34(7), 921-931.
Abstract:
An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults.
OBJECTIVE: the identification of modifiable lifestyle factors to preserve cognitive function in older individuals becomes increasingly of importance. This study examines whether word puzzle use is related to cognitive function in older adults. METHODS: Cognitive data from 19 078 cognitively healthy individuals aged 50 to 93 years enrolled into the online PROTECT study were evaluated for self-reported frequency of performing word puzzles on a six-point scale, ranging from "more than once per day" to "never". Nine cognitive tests covered a range of domains including focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analyses of covariance were used to determine any differences between the six response groups. RESULTS: Each of the 14 cognitive measures analysed showed highly statistically significant main effects of the frequency of performing word puzzles. For each measure, the group who never performed word puzzles performed most poorly, with the group who reported occasional puzzle use also performing more poorly than virtually every other group. Measures of speed provided the greatest discriminations, with a grammatical reasoning score differentiating the two highest frequency groups, performing word puzzles daily or more than once daily. CONCLUSIONS: the frequency of word puzzle use is directly related to cognitive function in adults aged 50 and over. Future work needs to determine whether engaging in such puzzles can favourably influence cognitive trajectory with age.
Abstract.
Author URL.
Ballard C, Allan L, Corbett A, Creese B, Brooker H, Fox C, Sami S, Shepstone L, Khondoker M, Richardson K, et al (2019). Big data in cohorts to understand the interaction of biological and psychosocial factors to prevent dementia.
INTERNATIONAL PSYCHOGERIATRICS,
31, 158-158.
Author URL.
Ballard C, Corbett A (2019). Commentary: Opportunities for Combination Trials.
J Prev Alzheimers Dis,
6(3), 177-178.
Author URL.
Newman L, Stoner C, Corbett A, Megalogeni M, Khan Z, Spector A (2019). Development of the ‘SNS older adults measure’ (SNS-OA) to examine social network site use in older adults. Aging & Mental Health, 25(1), 68-77.
Ballard C, Allan L, Corbett A, Creese B, Brooker H, Fox C, Sami S, Shepstone L, Khondoker M, Richardson K, et al (2019). Interaction of Biological and Psychosocial Factors in Dementia.
Author URL.
Eraydin IE, Mueller C, Corbett A, Ballard C, Brooker H, Wesnes K, Aarsland D, Huntley J (2019). Investigating the relationship between age of onset of depressive disorder and cognitive function.
Int J Geriatr Psychiatry,
34(1), 38-46.
Abstract:
Investigating the relationship between age of onset of depressive disorder and cognitive function.
OBJECTIVES: Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance. METHODS: This study examined baseline cross-sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early-onset, midlife-onset, and late-onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models. RESULTS: the late-onset depression group scored significantly lower on the verbal reasoning task than the early-onset group while there were no significant differences found on the other tasks. Midlife-onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early-onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks. CONCLUSIONS: the most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late-onset depression may be associated with more executive impairment than an early-onset depression.
Abstract.
Author URL.
Testad I, Kajander M, Froiland CT, Corbett A, Gjestsen MT, Anderson JG (2019). Nutritional Interventions for Persons with Early-Stage Dementia or Alzheimer's Disease: an Integrative Review.
Res Gerontol Nurs,
12(5), 259-268.
Abstract:
Nutritional Interventions for Persons with Early-Stage Dementia or Alzheimer's Disease: an Integrative Review.
Persons with Alzheimer's disease and related dementias (ADRD) are at particular risk of malnutrition and weight loss. Clinical research concerning the role and impact of nutritional intervention in early-stage ADRD, specifically on cognition and key symptoms such as behavior, is less straightforward. Thus, an integrative review was conducted to examine the literature pertaining to nutritional interventions for persons with ADRD and to make recommendations for priority areas for future research and practice. Findings from the studies reviewed highlight multiple potential opportunities for improving nutritional status and support for persons with ADRD living in the community. Despite the small amount of evidence, the six studies identified in the current review suggest a broad benefit may be conferred through educational approaches and nutritional supplementation. [Res Gerontol Nurs. 2019; 12(5):259-268.].
Abstract.
Author URL.
Creese BA, Griffiths A, Brooker H, Corbett A, Aarsland D, Ballard C, Ismail Z (2019). Profile of Mild Behavioral Impairment and Factor Structure of the Mild Behavioral Impairment Checklist in Cognitively Normal Older Adults. International Psychogeriatrics
Creese B, Griffiths A, Brooker H, Corbett A, Aarsland D, Ballard C, Ismail Z (2019). Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults.
International Psychogeriatrics,
32(6), 705-717.
Abstract:
Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults
ABSTRACTObjectives:In this large population study, we set out to examine the profile of mild behavioral impairment (MBI) by using the Mild Behavioral Impairment Checklist (MBI-C) and to explore its factor structure when employed as a self-reported and informant-rated tool.Design:This was a population-based cohort study.Setting:Participants were recruited from the Platform for Research Online to Investigate Genetics and Cognition in Aging study (https://www.protect-exeter.org.uk).Participants:A total of 5,742 participant-informant dyads participated in the study.Measurements:Both participants and informants completed the MBI-C. The factor structure of the MBI-C was evaluated by exploratory factor analysis.Results:The most common MBI-C items, as rated by self-reported and informants, related to affective dysregulation (mood/anxiety symptoms), being present in 34% and 38% of the sample, respectively. The least common items were those relating to abnormal thoughts and perception (psychotic symptoms) (present in 3% and 6% of the sample, respectively). Only weak correlations were observed between self-reported and informant-reported MBI-C responses. Exploratory factor analysis for both sets of respondent answers indicated that a five-factor solution for the MBI-C was appropriate, reflecting the hypothesized structure of the MBI-C.Conclusion:This is the largest and most detailed report on the frequency of MBI symptoms in a nondementia sample. The full spectrum of MBI symptoms was present in our sample, whether rated by self-reported or informant report. However, we show that the MBI-C performs differently in self-reported versus informant-reported situations, which may have important implications for the use of the questionnaire in clinic and research.
Abstract.
Brooker H, Wesnes KA, Ballard C, Hampshire A, Aarsland D, Khan Z, Stenton R, Megalogeni M, Corbett A (2019). The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over.
Int J Geriatr Psychiatry,
34(7), 932-940.
Abstract:
The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over.
OBJECTIVE: Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number-puzzle use is related to cognitive function in older adults. METHODS: Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self-reported frequency of performing number puzzles. Two cognitive-test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups. RESULTS: Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant. CONCLUSIONS: This study has identified a close relationship between frequency of number-puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.
Abstract.
Author URL.
2018
Lane CA, Hardy J, Schott JM (2018). Alzheimer's disease.
EUROPEAN JOURNAL OF NEUROLOGY,
25(1), 59-70.
Author URL.
Nunez KM, Khan Z, Testad I, Lawrence V, Creese B, Corbett A (2018). Current practice and challenges in night-time care for people with dementia living in care homes: a qualitative study.
Int J Geriatr Psychiatry,
33(1), e140-e149.
Abstract:
Current practice and challenges in night-time care for people with dementia living in care homes: a qualitative study.
OBJECTIVE: to explore the current practices and challenges in night-time care for people with dementia living in care homes in the UK. METHODS: Focus group discussions (FGD) were held with care staff and family carers from five care homes in South London. To supplement the FGD data, an online survey was circulated to family carers (n = 16), and informal interviews were conducted with night-time care staff and nurses (n = 19). The questions for the online survey were designed to specifically explore the themes that emerged from the FGD. RESULTS: Thematic analysis revealed eight key themes in the management of sleep disturbance in people with dementia living in care homes: current night-time care practices, dissonance in perceived causes of sleep disturbances, inconsistencies in treatment options, insufficient staffing levels, working relationships between shifts, nurse burden and responsibility, communication as a critical challenge, connecting with residents and one overarching theme of balance. CONCLUSIONS: the findings of this study highlight the need for an evidence-based sleep disturbance management programme designed for use in care homes and informed by stakeholders. The key themes identified represent the major barriers to good quality care and areas which future programmes will need to address to improve the quality of night-time care in care homes. There are clearly opportunities for future examination of non-pharmacological night-time care management programmes for use in the population. Copyright © 2017 John Wiley & Sons, Ltd.
Abstract.
Author URL.
Corbett A, Ballard C, Creese BA (2018). Evidence-based management of behavioural and psychological symptoms of dementia. In Michel J-P, Beattie BL, Martin FC, Walston JD (Eds.)
Oxford Textbook of Geriatric Medicine, Oxford University Press, 1015-1020.
Abstract:
Evidence-based management of behavioural and psychological symptoms of dementia
Abstract.
Petyaeva A, Kajander M, Lawrence V, Clifton L, Thomas AJ, Ballard C, Leroi I, Briggs M, Closs J, Dening T, et al (2018). Feasibility of a staff training and support programme to improve pain assessment and management in people with dementia living in care homes.
Int J Geriatr Psychiatry,
33(1), 221-231.
Abstract:
Feasibility of a staff training and support programme to improve pain assessment and management in people with dementia living in care homes.
OBJECTIVES: the objective of this study was to establish the feasibility and initial effectiveness of training and support intervention for care staff to improve pain management in people with dementia living in care homes (PAIN-Dem). METHODS: PAIN-Dem training was delivered to care staff from three care homes in South London, followed by intervention support and resources to encourage improved pain management by staff over 4 weeks. Feasibility was assessed through fidelity to intervention materials and qualitative approaches. Focus group discussions with staff explored the use of the PAIN-Dem intervention, and interviews were held with six residents and family carers. Pain was assessed in all residents at baseline, 3 and 4 weeks, and goal attainment scaling was assessed at 4 weeks. RESULTS: Delivery of training was a key driver for success and feasibility of the PAIN-Dem intervention. Improvements in pain management behaviour and staff confidence were seen in homes where training was delivered in a care home setting across the care team with good manager buy-in. Family involvement in pain management was highlighted as an area for improvement. Goal attainment in residents was significantly improved across the cohort, although no significant change in pain was seen. CONCLUSIONS: This study shows good initial feasibility of the PAIN-Dem intervention and provides valuable insight into training and support paradigms that deliver successful learning and behaviour change. There is a need for a larger trial of PAIN-Dem to establish its impact on resident pain and quantifiable staff behaviour measures. Copyright © 2017 John Wiley & Sons, Ltd.
Abstract.
Author URL.
Ballard C, Corbett A, Orrell M, Williams G, Moniz-Cook E, Romeo R, Woods B, Garrod L, Testad I, Woodward-Carlton B, et al (2018). Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial.
PLoS Med,
15(2).
Abstract:
Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial.
BACKGROUND: Agitation is a common, challenging symptom affecting large numbers of people with dementia and impacting on quality of life (QoL). There is an urgent need for evidence-based, cost-effective psychosocial interventions to improve these outcomes, particularly in the absence of safe, effective pharmacological therapies. This study aimed to evaluate the efficacy of a person-centred care and psychosocial intervention incorporating an antipsychotic review, WHELD, on QoL, agitation, and antipsychotic use in people with dementia living in nursing homes, and to determine its cost. METHODS AND FINDINGS: This was a randomised controlled cluster trial conducted between 1 January 2013 and 30 September 2015 that compared the WHELD intervention with treatment as usual (TAU) in people with dementia living in 69 UK nursing homes, using an intention to treat analysis. All nursing homes allocated to the intervention received staff training in person-centred care and social interaction and education regarding antipsychotic medications (antipsychotic review), followed by ongoing delivery through a care staff champion model. The primary outcome measure was QoL (DEMQOL-Proxy). Secondary outcomes were agitation (Cohen-Mansfield Agitation Inventory [CMAI]), neuropsychiatric symptoms (Neuropsychiatric Inventory-Nursing Home Version [NPI-NH]), antipsychotic use, global deterioration (Clinical Dementia Rating), mood (Cornell Scale for Depression in Dementia), unmet needs (Camberwell Assessment of Need for the Elderly), mortality, quality of interactions (Quality of Interactions Scale [QUIS]), pain (Abbey Pain Scale), and cost. Costs were calculated using cost function figures compared with usual costs. In all, 847 people were randomised to WHELD or TAU, of whom 553 completed the 9-month randomised controlled trial. The intervention conferred a statistically significant improvement in QoL (DEMQOL-Proxy Z score 2.82, p = 0.0042; mean difference 2.54, SEM 0.88; 95% CI 0.81, 4.28; Cohen's D effect size 0.24). There were also statistically significant benefits in agitation (CMAI Z score 2.68, p = 0.0076; mean difference 4.27, SEM 1.59; 95% CI -7.39, -1.15; Cohen's D 0.23) and overall neuropsychiatric symptoms (NPI-NH Z score 3.52, p < 0.001; mean difference 4.55, SEM 1.28; 95% CI -7.07,-2.02; Cohen's D 0.30). Benefits were greatest in people with moderately severe dementia. There was a statistically significant benefit in positive care interactions as measured by QUIS (19.7% increase, SEM 8.94; 95% CI 2.12, 37.16, p = 0.03; Cohen's D 0.55). There were no statistically significant differences between WHELD and TAU for the other outcomes. A sensitivity analysis using a pre-specified imputation model confirmed statistically significant benefits in DEMQOL-Proxy, CMAI, and NPI-NH outcomes with the WHELD intervention. Antipsychotic drug use was at a low stable level in both treatment groups, and the intervention did not reduce use. The WHELD intervention reduced cost compared to TAU, and the benefits achieved were therefore associated with a cost saving. The main limitation was that antipsychotic review was based on augmenting processes within care homes to trigger medical review and did not in this study involve proactive primary care education. An additional limitation was the inherent challenge of assessing QoL in this patient group. CONCLUSIONS: These findings suggest that the WHELD intervention confers benefits in terms of QoL, agitation, and neuropsychiatric symptoms, albeit with relatively small effect sizes, as well as cost saving in a model that can readily be implemented in nursing homes. Future work should consider how to facilitate sustainability of the intervention in this setting. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62237498.
Abstract.
Author URL.
Huntley J, Corbett A, Wesnes K, Brooker H, Stenton R, Hampshire A, Ballard C (2018). Online assessment of risk factors for dementia and cognitive function in healthy adults.
Int J Geriatr Psychiatry,
33(2), e286-e293.
Abstract:
Online assessment of risk factors for dementia and cognitive function in healthy adults.
OBJECTIVE: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. METHOD: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. RESULTS: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. CONCLUSION: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan.
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Svendsboe EJ, Testad I, Terum T, Jörg A, Corbett A, Aarsland D, Rongve A (2018). Patterns of carer distress over time in mild dementia.
Int J Geriatr Psychiatry,
33(7), 987-993.
Abstract:
Patterns of carer distress over time in mild dementia.
OBJECTIVE: to study the level of carer reported distress in mild dementia, over a 3-year period. METHODS: This study is part of the Norwegian DemVest-study and utilises data from carers of people with mild dementia (n = 223). Those diagnosed with dementia with Lewy bodies (DLB, n = 63) and Alzheimer's disease (AD, n = 97) were included together with other dementia types (n = 63). The Relatives' Stress Scale was used to assess the level of reported distress in carers. Descriptive and a linear mixed effects models including diagnosis, time, and the interaction between time and diagnosis were performed. RESULTS: Carer distress in mild dementia increased significantly over time (P = 0.011), particularly from baseline until 2 (P = 0.001) years follow-up. Carer distress in people caring for those with AD increased significantly, from baseline until 2 (P = 0.047) and 3 (P = 0.019) years follow-up. Distress in carers of people with DLB was high at baseline and remained relatively stable across the 3-year period. However, admission to a nursing home during the first year of follow-up was associated with a significantly lower reported carer distress in those caring for a person with DLB (P = 0.002), compared with those caring for a person with DLB living at home. CONCLUSION: Being a carer to a person with mild dementia is associated with increasing distress. However, the burden of distress changes with the diagnosis, time, and situation, which highlights the dynamic nature of the caring role. Findings have important implications for health services for people diagnosed with mild dementia and their carers.
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2017
Austbø Holteng LB, Frøiland CT, Corbett A, Testad I (2017). Care staff perspective on use of texture modified food in care home residents with dysphagia and dementia.
Ann Palliat Med,
6(4), 310-318.
Abstract:
Care staff perspective on use of texture modified food in care home residents with dysphagia and dementia.
BACKGROUND: Dysphagia and dementia are conditions, which combined, can lead to complications for the person and require good nutritional care. There is very little evidence-based literature regarding nutritional care for people with dysphagia and dementia. It is clear that care staff plays a vital role, and that communication and informed decision-making are critical to the process, yet little is known regarding the use of available interventions such as texture modified food (TMF), and their acceptability and feasibility for care staff and residents. Therefore the aim of this study was to investigate the experiences of care staff when providing nutritional care for people with dysphagia and dementia, and their impressions and experience of using TMF as a new intervention for nutrition. METHODS: This was a qualitative study with an inductive approach, which aimed to explore the experience of care staff using TMF in a care home setting. Data were collected using focus group interviews, an approach which is validated as a means of supporting and developing the understanding of a phenomenon, through interactions and discussions in the group. Participants were care staff working in a care home setting in Norway. RESULTS: Twelve participants were recruited to this study across two focus groups. The cohort included four nurses, six practical nurses, one nurse assistants and one student nurse. Four main categories emerged from the focus group discussions regarding the use of TMF. These were: (I) emotional strain; (II) deficient nutritional care; (III) increased self-efficacy with use of TMF; (IV) better nutritional care with TMF. CONCLUSIONS: Use of TMF to improve nutritional care for people with dysphagia appears to have merit for both residents and care staff, and should be considered as a means of improving nutritional care for people with dementia in care homes. Minimizing feeding difficulties and increasing nutritional intake is an important goal when caring for this vulnerable group of people, and there is a need to provide better training and support for care staff to ensure they feel confident and empowered to provide high quality nutritional care. The existing Norwegian Directorate of Health checklist for nutritional care may provide a helpful basis for improvements to guidance that accounts for the needs of staff and institutions. Further research and evaluation of an intervention for tailored nutritional care is warranted to improve this critical aspect of dementia care.
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Author URL.
Svendsboe E, Terum T, Testad I, Aarsland D, Ulstein I, Corbett A, Rongve A (2017). Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease (vol 31, pg 1075, 2016).
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
32(4), 470-470.
Author URL.
Khan A, Corbett A, Ballard C (2017). Emerging amyloid and tau targeting treatments for Alzheimer's disease.
Expert Rev Neurother,
17(7), 697-711.
Abstract:
Emerging amyloid and tau targeting treatments for Alzheimer's disease.
With an ageing global population, the number of people with dementia, and its main cause Alzheimer's disease (AD), is growing. current licensed treatments available for ad are only alleviate the symptoms of the disease, and are effective only in some people with ad for a limited time. there are currently no therapies that target the disease process. Areas covered: This review summarizes the available treatments for AD and the emerging therapies in the clinical trials pipeline. There are ongoing trials at various stages of development, targeting different mechanisms and pathways implicated in the disease. This review focuses on amyloid and tau targeting drug candidates. Expert commentary: Despite research efforts targeted at understanding AD, the underlying mechanisms and optimal treatment targets have not been fully elucidated. There is a significant need for further research targeting the disease at an earlier stage and progress in biomarker and imaging technology are improving the outlook. It is critical to continue research into identifying the underlying pathology and disease process in Alzheimer's disease to enable development of effective targeted treatments.
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Khan A, Corbett A, Ballard C (2017). Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
Expert Rev Neurother,
17(7), 683-695.
Abstract:
Emerging treatments for Alzheimer's disease for non-amyloid and non-tau targets.
The number of people with dementia, including Alzheimer's disease, is growing as a result of an ageing global population. Treatments available for AD only alleviate the symptoms of the disease, and are effective in some people with AD for a limited time. There is no disease-modifying treatment available, and despite research efforts, the underlying mechanisms of AD and optimal treatment targets have not been fully elucidated. Amyloid and tau are key pathological markers of AD with ongoing trials targeting both. However, there are also many trials at various stages of development that primarily target other markers and processes implicated in the disease, which are now being investigated. Areas covered: This review summarizes current treatment approaches for AD and explores both repositioned and novel therapies that target non amyloid and non tau mechanisms that are in the clinical trials pipeline. This includes treatments for cognitive and neuropsychiatric symptoms and potentially disease modifying therapies. The studies included in this review have been obtained from searches of PubMed and clinical trials databases. Expert commentary: There is a renewed energy in identifying better treatments for behavioural symptoms of AD using both novel drugs and repositioning existing drugs. Lack of success in clinical trials of drugs targeting amyloid and tau have led to a surge in targeting alternative mechanisms. Progress in the development of biomarkers will provide further tools for clinical trials of potential therapeutics for both symptomatic treatment and disease modification in AD.
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Rajkumar AP, Ballard C, Fossey J, Orrell M, Moniz-Cook E, Woods RT, Murray J, Whitaker R, Stafford J, Knapp M, et al (2017). Epidemiology of Pain in People with Dementia Living in Care Homes: Longitudinal Course, Prevalence, and Treatment Implications.
J Am Med Dir Assoc,
18(5), 453.e1-453.e6.
Abstract:
Epidemiology of Pain in People with Dementia Living in Care Homes: Longitudinal Course, Prevalence, and Treatment Implications.
INTRODUCTION: Knowledge regarding the longitudinal course, impact, or treatment implications of pain in people with dementia living in care homes is very limited. METHODS: We investigated the people with dementia living in 67 care homes in London and Buckinghamshire, United Kingdom. Pain, dementia severity, neuropsychiatric symptoms, depression, agitation, and quality-of-life were measured using appropriate instruments at baseline (N = 967) and after 9 months (n = 629). RESULTS: Baseline prevalence of pain was 35.3% (95% CI 32.3-38.3). Pain severity was significantly correlated with dementia severity, neuropsychiatric symptoms, depression, agitation, and quality of life at both time points. Regular treatment with analgesics significantly reduced pain severity. Pain was significantly associated with more antipsychotic prescriptions. Pain was significantly associated (OR 1.48; 95% CI 1.18-1.85) with all-cause mortality during follow-up. CONCLUSIONS: Pain is an important determinant of neuropsychiatric symptoms, mortality, quality-of-life, and antipsychotic prescriptions. Improved identification, monitoring, and treatment of pain are urgent priorities to improve the health and quality-of-life for people with dementia.
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Drageset J, Eide GE, Corbett A (2017). Health-related quality of life among cognitively intact nursing home residents with and without cancer - a 6-year longitudinal study.
Patient Relat Outcome Meas,
8, 63-69.
Abstract:
Health-related quality of life among cognitively intact nursing home residents with and without cancer - a 6-year longitudinal study.
BACKGROUND: Limited information exists regarding the natural development of health-related quality of life (HRQOL) and its determinants among mentally intact nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year period among residents of NHs, who are not cognitively impaired, and to examine whether sense of coherence and a diagnosis of cancer influence HRQOL. METHODS: the study was prospective and included baseline assessment and 6-year follow-up. After baseline assessment of 227 cognitively intact NH residents (Clinical Dementia Rating score ≤ 0.5), we interviewed 52 living respondents a second time at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up. We recorded data from the interviews using the Short Form-36 (SF-36) Health Survey and the Sense of Coherence Scale. To study different developments over time for residents without and with cancer, we tested interactions between cancer and time. RESULTS: the subscores of physical functioning and role limitation-physical domains declined with time (P < 0.001 and P = 0.02, respectively). Having a diagnosis of cancer at baseline was negatively correlated with general health (P = 0.002). Sense of coherence at baseline was positively correlated with all the SF-36 subscores from baseline to follow-up (P < 0.001). CONCLUSION: the study indicates that the HRQOL changed over time during the 6 years of follow-up, and the sense of coherence appeared to be an important component of the HRQOL. Finally, our results showed that having a diagnosis of cancer was associated with decline in the general health subdimension.
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Mueller C, Ballard C, Corbett A, Aarsland D (2017). Historical landmarks in dementia with Lewy bodies.
Lancet Neurol,
16(5).
Author URL.
Ballard C, Orrell M, Sun Y, Moniz-Cook E, Stafford J, Whitaker R, Woods B, Corbett A, Banerjee S, Testad I, et al (2017). Impact of antipsychotic review and non-pharmacological intervention on health-related quality of life in people with dementia living in care homes: WHELD-a factorial cluster randomised controlled trial.
Int J Geriatr Psychiatry,
32(10), 1094-1103.
Abstract:
Impact of antipsychotic review and non-pharmacological intervention on health-related quality of life in people with dementia living in care homes: WHELD-a factorial cluster randomised controlled trial.
BACKGROUND: Very few interventional studies have directly examined the impact of treatment approaches on health-related quality of life (HRQL) in people with dementia. This is of particular importance in therapies to address behavioural symptoms, where HRQL is often severely affected. METHODS: Analysis within the WHELD cluster randomised factorial study in 16 UK care homes examining the impact of person-centred care in combination with antipsychotic review, social interaction and exercise interventions. This study analysed impact on HRQL through the DEMQOL-Proxy. RESULTS: Data on HRQL were available for 187 participants. People receiving antipsychotic review showed a significant worsening in two DEMQOL-Proxy domains (negative emotion: p = 0.02; appearance: p = 0.04). A best-case scenario analysis showed significant worsening for total DEMQOL-Proxy score. Social interaction intervention resulted in a significant benefit to HRQL (p = 0.04). There was no deterioration in HRQL in groups receiving both antipsychotic review and social interaction (p = 0.62). CONCLUSIONS: This demonstrates an important detrimental impact of discontinuation of antipsychotics in dementia on HRQL, highlighting the need for careful review of best practice guidelines regarding antipsychotic use and emphasising the importance of providing evidence-based non-pharmacological interventions in conjunction with antipsychotic review. Copyright © 2016 John Wiley & Sons, Ltd.
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Gatt A, Ekonomou A, Somani A, Thuret S, Howlett D, Corbett A, Johnson M, Perry E, Attems J, Francis P, et al (2017). Importance of Proactive Treatment of Depression in Lewy Body Dementias: the Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study.
Dement Geriatr Cogn Disord,
44(5-6), 283-293.
Abstract:
Importance of Proactive Treatment of Depression in Lewy Body Dementias: the Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study.
OBJECTIVE: to examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). METHODS: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). RESULTS: DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. CONCLUSION: SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.
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Flo E, Bjorvatn B, Corbett A, Pallesen S, Husebo BS (2017). Joint Occurrence of Pain and Sleep Disturbances in People with Dementia. A Systematic Review.
Curr Alzheimer Res,
14(5), 538-545.
Abstract:
Joint Occurrence of Pain and Sleep Disturbances in People with Dementia. A Systematic Review.
BACKGROUND: Advancing age is associated with high prevalence of pain, sleep problems and dementia. Dementia is frequently accompanied by distressing behavioral and psychological symptoms, including sleep problems. The etiology of sleep problems in dementia is multifactorial. It has been suggested that untreated pain may contribute to sleep problems, and pain treatment has been shown to reduce sleep problems in people with dementia. OBJECTIVE: This systematic review aims to provide an overview of the studies that have investigated the association and/or possible interaction between pain and sleep in dementia. METHODS: a systematic search was performed in MEDLINE, EMBASE, Cochrane and PsychINFO, including text words and MESH terms covering dementia, pain and sleep. Also, reference lists in the included publications were examined to retrieve publications. Publications had to investigate sleep and pain in relation to dementia to be included in this review. RESULTS: the search produced 1750 independent hits. Out of the 49 publications studied in full text, 11 publications were included. Only one controlled trial was identified and represented the only insights to the possible interactional relationship between pain, sleep and dementia. Pain or pain intensity were related to sleep in 6 of the included studies, while the remaining studies could neither support nor contradict a relationship between sleep and pain in people with dementia. None of the studies employed objective sleep assessment. CONCLUSION: There is a need for high quality studies investigating the interaction between sleep and pain in people with dementia, using objective sleep measurements and pain assessment suitable for people with dementia.
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Drageset J, Eide GE, Corbett A (2017). Patterns of health-related quality of life among nursing home residents with and without cancer.
Author URL.
Mueller C, Ballard C, Corbett A, Aarsland D (2017). The prognosis of dementia with Lewy bodies.
Lancet Neurol,
16(5), 390-398.
Abstract:
The prognosis of dementia with Lewy bodies.
Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimer's disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimer's disease. It is probable that causative factors for this less favourable prognosis are the increased prevalence and early emergence of neuropsychiatric symptoms in patients with dementia with Lewy bodies, and the challenge of accurate diagnosis. Evidence concerning quality of life and hospital admission rates is limited, despite their clinical and economic relevance.
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Wesnes KA, Brooker H, Ballard C, McCambridge L, Stenton R, Corbett A (2017). Utility, reliability, sensitivity and validity of an online test system designed to monitor changes in cognitive function in clinical trials.
Int J Geriatr Psychiatry,
32(12), e83-e92.
Abstract:
Utility, reliability, sensitivity and validity of an online test system designed to monitor changes in cognitive function in clinical trials.
OBJECTIVE: the advent of long-term remotely conducted clinical trials requires assessments which can be administered online. This paper considers the utility, reliability, sensitivity and validity of an internet-based system for measuring changes in cognitive function which is being used in one such trial. METHODS: the Platform for Research Online to investigate Genetics and Cognition in Ageing is a 10-year longitudinal and entirely remote study launched in November 2015. The CogTrackTM System is being used to monitor changes in important aspects of cognitive function using tests of attention, information processing and episodic memory. On study entry, the participants performed CogTrackTM up to three times over seven days, and these data are evaluated in this paper. RESULTS: During the first six months of the study, 14 531 individuals aged 50 to 94 years enrolled and performed the CogTrackTM System, 8627 of whom completed three test sessions. On the first administration, 99.4% of the study tasks were successfully completed. Repeated testing showed training/familiarisation effects on four of the ten measures which had largely stabilised by the third test session. The factor structure of the various measures was found to be robust. Evaluation of the influence of age identified clinically relevant declines over the age range of the population on one or more measures from all tasks. CONCLUSIONS: the results of these analyses identify CogTrackTM to be a practical and valid method to reliably, sensitively, remotely and repeatedly collect cognitive data from large samples of individuals aged 50 and over. Copyright © 2017 John Wiley & Sons, Ltd.
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Clare L, Kudlicka A, Bayer A, Jones RW, John Knapp MR, Kopelman M, Leroi I, Oyebode J, Pool J, Woods B, et al (2017). [O3–02–05]: GOAL‐ORIENTED COGNITIVE REHABILITATION IN EARLY‐STAGE ALZHEIMER's AND RELATED DEMENTIAS: RESULTS FROM a MULTI‐CENTRE, SINGLE‐BLIND, RANDOMISED CONTROLLED TRIAL (THE GREAT TRIAL). Alzheimer's & Dementia, 13(7S_Part_18).
2016
Greenan C, Murphy L, Yu L-M, Kehoe PG, Coulthard E, Bath P, Stewart R, Jones R, Corbett A, Thomas A, et al (2016). A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
Trials,
17(1).
Abstract:
A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol.
BACKGROUND: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia. METHODS/DESIGN: This is a randomised controlled trial of calcium channel blockade with Amlodipine for the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks. DISCUSSION: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31208535. Registered on 7 March 2014.
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Rajkumar AP, Ballard C, Fossey J, Corbett A, Woods B, Orrell M, Prakash R, Moniz-Cook E, Testad I (2016). Apathy and its Response to Antipsychotic Review and Nonpharmacological Interventions in People with Dementia Living in Nursing Homes: WHELD, a Factorial Cluster Randomized Controlled Trial.
Journal of the American Medical Directors Association,
17(8), 741-747.
Abstract:
Apathy and its Response to Antipsychotic Review and Nonpharmacological Interventions in People with Dementia Living in Nursing Homes: WHELD, a Factorial Cluster Randomized Controlled Trial
Objectives Apathy is common, impactful, and difficult to manage in people with dementia. We evaluated the efficacy of nonpharmacological interventions, exercise, and social interaction, in combination with antipsychotic review, to reduce apathy in people with dementia living in nursing homes in a cluster randomized controlled trial (RCT). Methods Well-being and health for people with dementia (WHELD) program included a 2 × 2 × 2 factorial cluster RCT involving people with dementia living in 16 nursing homes in the United Kingdom. All homes received training in person-centered care, and were randomized to receive antipsychotic review, social interaction, and exercise, either alone or in combinations. Apathy was one of the secondary outcomes of the WHELD trial, and it was measured by the Neuropsychiatric Inventory–nursing home version at baseline and 9 months (n = 273). We used multilevel mixed effects linear regression models to assess the impact of the interventions on apathy. Results Prevalence of apathy was 44.0% (n = 120; 95% confidence interval [CI] 38.1%–49.9%) at baseline. Severity of apathy had significant positive correlations with dementia severity, neuropsychiatric symptoms, depressive symptoms, agitation, and the needs of the people with dementia (P
Abstract.
Svendsboe E, Terum T, Testad I, Aarsland D, Ulstein I, Corbett A, Rongve A (2016). Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease.
Int J Geriatr Psychiatry,
31(9), 1075-1083.
Abstract:
Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease.
OBJECTIVE: to characterise the differences in caregiver distress between carers of people diagnosed with dementia with Lewy bodies (DLB) and people with Alzheimer's disease (AD), with a view to differentiating and improving support for caregivers. METHODS: This study is a part of two larger Norwegian studies, DemVest (n = 265) and the Norwegian Dementia Register (n = 2220), with data from caregivers and people diagnosed with AD (n = 100) and DLB (n = 86) between 2005 and 2013. The average age was 74.9 years (SD = 7.8). Caregiver distress was rated by the Relative Stress Scale. Diagnosis of the person receiving care was based on a comprehensive standardised assessment program (International Classification of Diseases, Revision 10 or Diagnostic and Statistical Manual for Mental Disorders, fourth edition). Additional data collected from people receiving care were neuropsychiatric symptoms, comorbidity and activities of daily living (ADL) score. Linear regression analyses were applied, first unadjusted and then in stepwise-adjusts in addition to descriptive analyses. RESULTS: Caregivers to people with AD (20.2%) and 40% of caregivers for people with DLB experienced moderate or high caregiver burden with an increased risk of psychiatric disorders in the early stage of dementia. High Relative Stress Scale (RSS) total scores in caregivers was significantly associated with neuropsychiatric symptoms (Neuropsychiatric Inventory, p = 0.004) and also with impaired ADL functioning (Rapid Disability Rating Scale-2, p
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Ballard C, Mobley W, Hardy J, Williams G, Corbett A (2016). Dementia in Down's syndrome.
Lancet Neurol,
15(6), 622-636.
Abstract:
Dementia in Down's syndrome.
Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches.
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Corbett A, Ballard C (2016). Dextromethorphan and quinidine are suitable for off-label short-term treatment of agitation in people with Alzheimer's disease following first-line non-drug approaches.
Evid Based Med,
21(1).
Author URL.
Surr CA, Walwyn REA, Lilley-Kelly A, Cicero R, Meads D, Ballard C, Burton K, Chenoweth L, Corbett A, Creese B, et al (2016). Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial.
Trials,
17(1).
Abstract:
Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial.
BACKGROUND: up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. METHODS/DESIGN: a pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. DISCUSSION: the protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015.
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Ballard C, Orrell M, YongZhong S, Moniz-Cook E, Stafford J, Whittaker R, Woods B, Corbett A, Garrod L, Khan Z, et al (2016). Impact of Antipsychotic Review and Nonpharmacological Intervention on Antipsychotic Use, Neuropsychiatric Symptoms, and Mortality in People with Dementia Living in Nursing Homes: a Factorial Cluster-Randomized Controlled Trial by the Well-Being and Health for People with Dementia (WHELD) Program.
Am J Psychiatry,
173(3), 252-262.
Abstract:
Impact of Antipsychotic Review and Nonpharmacological Intervention on Antipsychotic Use, Neuropsychiatric Symptoms, and Mortality in People with Dementia Living in Nursing Homes: a Factorial Cluster-Randomized Controlled Trial by the Well-Being and Health for People with Dementia (WHELD) Program.
OBJECTIVE: This study evaluated the impact of antipsychotic review, social interaction, and exercise, in conjunction with person-centered care, on antipsychotic use, agitation, and depression in people with dementia living in nursing homes. METHOD: a cluster-randomized factorial controlled trial with two replications was conducted in people with dementia in 16 U.K. nursing homes. All homes received training in person-centered care. Eight homes were randomly assigned to antipsychotic review, to a social interaction intervention, and to an exercise intervention for 9 months, with most homes assigned to more than one intervention. The primary outcome measures were antipsychotic use, agitation, and depression. Secondary outcome measures were overall neuropsychiatric symptoms and mortality. RESULTS: Antipsychotic review significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval [CI] 0.05 to 0.60). Antipsychotic review plus the social interaction intervention significantly reduced mortality (odds ratio 0.26, 95% CI 0.13 to 0.51) compared with the group receiving neither. The group receiving antipsychotic review but not the social intervention showed significantly worse outcome in neuropsychiatric symptoms compared with the group receiving neither (score difference +7.37, 95% CI 1.53 to 13.22). This detrimental impact was mitigated by concurrent delivery of the social intervention (-0.44, CI -4.39 to 3.52). The exercise intervention significantly improved neuropsychiatric symptoms (-3.59, 95% CI -7.08 to -0.09) but not depression (-1.21, CI -4.35 to 1.93). None of the interventions had a significant impact specifically on agitation. CONCLUSIONS: While reductions in antipsychotic use can be achieved by using a "real world" intervention, this may not be of benefit to people with dementia in the current climate of more judicious prescribing unless nonpharmacological interventions such as social interaction or exercise are provided in parallel.
Abstract.
Author URL.
Lichtner V, Dowding D, Allcock N, Keady J, Sampson EL, Briggs M, Corbett A, James K, Lasrado R, Swarbrick C, et al (2016). The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective.
BMC Health Serv Res,
16(1).
Abstract:
The assessment and management of pain in patients with dementia in hospital settings: a multi-case exploratory study from a decision making perspective.
BACKGROUND: Pain is often poorly managed in people who have a dementia. Little is known about how this patient population is managed in hospital, with research to date focused mainly on care homes. This study aimed to investigate how pain is recognised, assessed and managed in patients with dementia in a range of acute hospital wards, to inform the development of a decision support tool to improve pain management for this group. METHODS: a qualitative, multi-site exploratory case study. Data were collected in four hospitals in England and Scotland. Methods included non-participant observations, audits of patient records, semi-structured interviews with staff and carers, and analysis of hospital ward documents. Thematic analysis was performed through the lens of decision making theory. RESULTS: Staff generally relied on patients' self-report of pain. For patients with dementia, however, communication difficulties experienced because of their condition, the organisational context, and time frames of staff interactions, hindered patients' ability to provide staff with information about their pain experience. This potentially undermined the trials of medications used to provide pain relief to each patient and assessments of their responses to these treatments. Furthermore, given the multidisciplinary environment, a patient's communication about their pain involved several members of staff, each having to make sense of the patient's pain as in an 'overall picture'. Information about patients' pain, elicited in different ways, at different times and by different health care staff, was fragmented in paper-based documentation. Re-assembling the pieces to form a 'patient specific picture of the pain' required collective staff memory, 'mental computation' and time. CONCLUSIONS: There is a need for an efficient method of eliciting and centralizing all pain-related information for patients with dementia, which is distributed in time and between personnel. Such a method should give an overall picture of a patient's pain which is rapidly accessible to all involved in their care. This would provide a much-needed basis for making decisions to support the effective management of the pain of older people with dementia in hospital.
Abstract.
Author URL.
Corbett A, Nunez K-M, Smeaton E, Testad I, Thomas AJ, Closs SJ, Briggs M, Clifton L, Gjestsen MT, Lawrence V, et al (2016). The landscape of pain management in people with dementia living in care homes: a mixed methods study.
Int J Geriatr Psychiatry,
31(12), 1354-1370.
Abstract:
The landscape of pain management in people with dementia living in care homes: a mixed methods study.
OBJECTIVES: the aim of this study is to explore the current landscape of pain management in people with dementia living in care home settings. Pain is extremely common in this patient group, yet there is very limited guidance for healthcare professionals. METHODS: Triangulation of stakeholder consultation and quality review of pain management guidance were performed. A review of existing pain management guidance was conducted using published quality criteria adapted for the field. Three focus group discussions were held with care home staff and two focus group discussions and an online survey with family carers. Data were subjected to thematic analysis to identify themes and sub-themes. Outcomes were reviewed by an expert panel, which gave recommendations. RESULTS: Fifteen existing guidelines were identified, of which three were designed for use in dementia and none were tailored for care home settings. Thematic analysis revealed six major themes in current pain management in dementia: importance of person-centredness, current lack of pain awareness in staff, communication as a core element, disparities in staff responsibility and confidence, the need for consistency of care and current lack of staff training. In addition to the needs for practice, the expert panel identified promising pharmacological treatment candidates, which warrant clinical evaluation. CONCLUSIONS: the findings of this study clearly articulate a need for an evidence-based pain management programme for care homes, which is informed by stakeholder input and based within a conceptual framework for this setting. There are novel opportunities for clinical trials of alternative analgesics for use in this patient group. Copyright © 2016 John Wiley & Sons, Ltd.
Abstract.
Author URL.
Closs SJ, Dowding D, Allcock N, Hulme C, Keady J, Sampson EL, Briggs M, Corbett A, Esterhuizen P, Holmes J, et al (2016). Towards improved decision support in the assessment and management of pain for people with dementia in hospital: a systematic meta-review and observational study.
Health Services and Delivery Research,
4(30), 1-162.
Abstract:
Towards improved decision support in the assessment and management of pain for people with dementia in hospital: a systematic meta-review and observational study
BackgroundPain and dementia are common in older people, and impaired cognitive abilities make it difficult for them to communicate their pain. Pain, if poorly managed, impairs health and well-being. Accurate pain assessment in this vulnerable group is challenging for hospital staff, but essential for appropriate management. Robust methods for identifying, assessing and managing pain are needed.Aims and objectivesTwo studies were undertaken to inform the development of a decision support tool to aid hospital staff in the recognition, assessment and management of pain. The first was a meta-review of systematic reviews of observational pain assessment instruments with three objectives: (1) to identify the tools available to assess pain in adults with dementia; (2) to identify in which settings they were used and with what patient populations; and (3) to assess their reliability, validity and clinical utility. The second was a multisite observational study in hospitals with four objectives: (1) to identify information currently used by clinicians when detecting and managing pain in patients with dementia; (2) to explore existing processes for detecting and managing pain in these patients; (3) to identify the role (actual/potential) of carers in this process; and (4) to explore the organisational context in which health professionals operate. Findings also informed development of health economics data collection forms to evaluate the implementation of a new decision support intervention in hospitals.MethodsFor the meta-review of systematic reviews, 12 databases were searched. Reviews of observational pain assessment instruments that provided psychometric data were included. Papers were quality assessed and data combined using narrative synthesis. The observational study used an ethnographic approach in 11 wards in four UK hospitals. This included non-participant observation of 31 patients, audits of patient records, semistructured interviews with 52 staff and four carers, informal conversations with staff and carers and analysis of ward documents and policies. Thematic analysis of the data was undertaken by the project team.ResultsData from eight systematic reviews including 28 tools were included in the meta-review. Most tools showed moderate to good reliability, but information about validity, feasibility and clinical utility was scarce. The observational study showed complex ward cultures and routines, with variations in time spent with patients, communication patterns and management practices. Carer involvement was rare. No pain decision support tools were observed in practice. Information about pain was elicited in different ways, at different times, by different health-care staff and recorded in separate documents. Individual staff made sense of patients’ pain by creating their own ‘overall picture’ from available information.LimitationsGrey literature and non-English-language papers were excluded from the meta-review. Sample sizes in the observational study were smaller than planned owing to poor documentation of patients’ dementia diagnoses, gatekeeping by staff and difficulties in gaining consent/assent. Many patients had no or geographically distant carers, or a spouse who was too unwell and/or reluctant to participate.ConclusionsNo single observational pain scale was clearly superior to any other. The traditional linear concept of pain being assessed, treated and reassessed by single individuals did not ‘fit’ with clinical reality. A new approach enabling effective communication among patients, carers and staff, centralised recording of pain-related information, and an extended range of pain management interventions is proposed [Pain and Dementia Decision Support (PADDS)]. This was not tested with users, but a follow-on study aims to codesign PADDS with carers and clinicians, then introduce education on staff/patient/carer communications and use of PADDS within a structured implementation plan. PADDS will need to be tested in differing ward contexts.FundingThe National Institute for Health Research Health Services and Delivery Research programme.
Abstract.
Khan A, Kalaria RN, Corbett A, Ballard C (2016). Update on Vascular Dementia.
J Geriatr Psychiatry Neurol,
29(5), 281-301.
Abstract:
Update on Vascular Dementia.
Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment.
Abstract.
Author URL.
2015
Ballard C, Thomas A, Gerry S, Yu L-M, Aarsland D, Merritt C, Corbett A, Davison C, Sharma N, Khan Z, et al (2015). A Double-Blind Randomized Placebo-Controlled Withdrawal Trial Comparing Memantine and Antipsychotics for the Long-Term Treatment of Function and Neuropsychiatric Symptoms in People with Alzheimer's Disease (MAIN-AD).
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION,
16(4), 316-322.
Author URL.
Ferreira N, Owen A, Mohan A, Corbett A, Ballard C (2015). Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
30(4), 422-430.
Author URL.
Ballard C, Sharp S, Corbett A (2015). Dextromethorphan and Quinidine for Treating Agitation in Patients with Alzheimer Disease Dementia.
JAMA,
314(12), 1233-1235.
Author URL.
Corbett A (2015). Drug repositioning in Alzheimer rsquo s disease. Frontiers in Bioscience, 7(1), 184-188.
Corbett A, Williams G, Ballard C (2015). Drug repositioning in Alzheimer's disease.
Front Biosci (Schol Ed),
7(1), 184-188.
Abstract:
Drug repositioning in Alzheimer's disease.
Drug repositioning offers an innovative approach to drug discovery with great potential in the field of Alzheimer's Disease and dementia therapeutics. Investigation of licensed compounds enables processing through the drug discovery pipeline in a rapid and cost-effective manner. A growing body of evidence supports the translation of priority compounds to be taken forward to clinical trials, based on established and proposed mechanisms of action. A number of drugs have already entered clinical trial following repositioning, and novel technologies have been created to enable high-throughput screening. This review discusses the novel approaches that build on transcriptional signature profiling to support repositioning in AD, and the novel candidate drugs that are emerging from this exciting new technique.
Abstract.
Author URL.
Creese B, Corbett A, DPhil EJ, Fox C, Ballard C (2015). Erratum to [Role of the Extended MAPT Haplotype in the Worsening of Psychotic Symptoms and Treatment Response in Alzheimer Disease, J Am Med Dir Assoc, 15, 12, (2014), 934-937], DOI: 10.1016/j.jamda.2014.08.011. Journal of the American Medical Directors Association, 16(3).
Ballard C, Isaacson S, Mills R, Williams H, Corbett A, Coate B, Pahwa R, Rascol O, Burn DJ (2015). Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People with Parkinson Disease Psychosis.
J Am Med Dir Assoc,
16(10), 898.e1-898.e7.
Abstract:
Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People with Parkinson Disease Psychosis.
OBJECTIVES: to establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. DESIGN: Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. SETTING: Primary and secondary care medical centers in the United States, Canada, Europe, and India. PARTICIPANTS: a total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. INTERVENTIONS: Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. MAIN OUTCOME MEASURES: Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. CONCLUSIONS: This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality.
Abstract.
Author URL.
Dowding D, Lichtner V, Esterhuizen P, Closs SJ, Long A, Corbett A, Briggs M (2015). Pain Assessment Tools for Individuals with Dementia: a Metareview.
Author URL.
Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, et al (2015). The Effect of an Online Cognitive Training Package in Healthy Older Adults: an Online Randomized Controlled Trial.
Journal of the American Medical Directors Association,
16(11), 990-997.
Author URL.
2014
Ballard C, Corbett A, Sharp S (2014). Aligning the evidence with practice: NICE guidelines for drug treatment of Alzheimer’s disease. Expert Review of Neurotherapeutics, 11(3), 327-329.
Corbett A, Achterberg W, Husebo B, Lobbezoo F, de Vet H, Kunz M, Strand L, Constantinou M, Tudose C, Kappesser J, et al (2014). An international road map to improve pain assessment in people with impaired cognition: the development of the Pain Assessment in Impaired Cognition (PAIC) meta-tool.
BMC Neurol,
14Abstract:
An international road map to improve pain assessment in people with impaired cognition: the development of the Pain Assessment in Impaired Cognition (PAIC) meta-tool.
BACKGROUND: Pain is common in people with dementia, yet identification is challenging. A number of pain assessment tools exist, utilizing observation of pain-related behaviours, vocalizations and facial expressions. Whilst they have been developed robustly, these often lack sufficient evidence of psychometric properties, like reliability, face and construct validity, responsiveness and usability, and are not internationally implemented. The EU-COST initiative "Pain in impaired cognition, especially dementia" aims to combine the expertise of clinicians and researchers to address this important issue by building on previous research in the area, identifying existing pain assessment tools for dementia, and developing consensus for items for a new universal meta-tool for use in research and clinical settings. This paper reports on the initial phase of this collaboration task. METHODS: all existing observational pain behaviour tools were identified and elements categorised using a three-step reduction process. Selection and refinement of items for the draft Pain Assessment in Impaired Cognition (PAIC) meta-tool was achieved through scrutiny of the evidence, consensus of expert opinion, frequency of use and alignment with the American Geriatric Society guidelines. The main aim of this process was to identify key items with potential empirical, rather than theoretical value to take forward for testing. RESULTS: 12 eligible assessment tools were identified, and pain items categorised according to behaviour, facial expression and vocalisation according to the AGS guidelines (Domains 1 - 3). This has been refined to create the PAIC meta-tool for validation and further refinement. A decision was made to create a supporting comprehensive toolkit to support the core assessment tool to provide additional resources for the assessment of overlapping symptoms in dementia, including AGS domains four to six, identification of specific types of pain and assessment of duration and location of pain. CONCLUSIONS: This multidisciplinary, cross-cultural initiative has created a draft meta-tool for capturing pain behaviour to be used across languages and culture, based on the most promising items used in existing tools. The draft PAIC meta-tool will now be taken forward for evaluation according to COSMIN guidelines and the EU-COST protocol in order to exclude invalid items, refine included items and optimise the meta-tool.
Abstract.
Author URL.
Sultana J, Chang CK, Hayes RD, Broadbent M, Stewart R, Corbett A, Ballard C (2014). Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study. International Journal of Geriatric Psychiatry, 29(12), 1249-1254.
Drageset J, Corbett A, Selbaek G, Husebo BS (2014). Cancer-related pain and symptoms among nursing home residents: a systematic review.
J Pain Symptom Manage,
48(4), 699-710.e1.
Abstract:
Cancer-related pain and symptoms among nursing home residents: a systematic review.
CONTEXT: Many older nursing home (NH) residents with cancer experience pain and distressing symptoms. Although some develop cancer during their time in the institution, an increasing number are admitted during their final stages of their lives. Numerous studies have evaluated various treatment approaches, but how pain and symptoms are assessed and managed in people with cancer with and without dementia is unclear. OBJECTIVES: the objective of this review was to summarize the evidence on cancer-related symptoms among NH residents with and without dementia. METHODS: We systematically searched the PubMed (1946-2012), Embase (1974-2012), CINAHL (1981-2012), AgeLine, and Cochrane Library (1998-2012) databases using the search terms neoplasms, cancer, tumor, and nursing home. The inclusion criteria were studies including NH residents with a diagnosis of cancer and outcome measures including pain and cancer-related symptoms. RESULTS: We identified 11 studies (cross-sectional, longitudinal, clinical trial, and qualitative studies). Ten studies investigated the prevalence and treatment of cancer-related symptoms such as vomiting, nausea, urinary tract infections, and depression. Studies clearly report a high prevalence of pain and reduced prescribing and treatment, regardless of the cognitive status. Only one small study included people with cancer and a diagnosis of dementia. Studies of new cancer diagnoses in NHs could not be identified. CONCLUSION: This review clearly reports a high prevalence of pain and reduced drug prescribing and treatment among NH residents with cancer. This issue appears to be most critical among people with severe dementia, emphasizing the need for better guidance and evidence on pain assessment for these individuals.
Abstract.
Author URL.
Khan Z, Corbett A, Ballard C (2014). Cognitive stimulation therapy: training, maintenance and implementation in clinical trials.
Pragmat Obs Res,
5, 15-19.
Abstract:
Cognitive stimulation therapy: training, maintenance and implementation in clinical trials.
There are around 35 million people worldwide with dementia, more than half of whom have Alzheimer's disease (AD). Presently there are only four licensed pharmacological treatments available for treating the neuropsychological symptoms of AD. These include cholinesterase inhibitors, licensed for the treatment of people with mild to moderate AD, and an N-methyl-D-aspartate antagonist (memantine) licensed for the treatment of people with moderate to severe AD. These treatment options have modest symptomatic benefits for at least 6 months and possibly for 2 years or longer. Increasing evidence from randomized controlled trials has shown the potential value of cognitive training and cognitive rehabilitation in people with AD. There is a good evidence base to support the use of cognitive stimulation as a nonpharmacological treatment approach for people with AD, of which the most promising is cognitive stimulation therapy (CST). CST has shown benefits for cognition and well-being in people with dementia across a number of randomized controlled trials. There are important key issues related to the use of CST for people with AD, such as long-term benefits, implementation of individualized CST, adjunctive benefits with pharmacological treatments, and optimizing overall implementation of CST. Some of these key issues are already being addressed by ongoing clinical trials. Nevertheless, the strength of the current evidence from randomized controlled trials gives strong support to clinical implementation of CST in practice. Ongoing clinical trials will help to refine and optimize the use of CST in clinical practice.
Abstract.
Author URL.
Husebo BS, Corbett A (2014). Dementia: Pain management in dementia--the value of proxy measures.
Nat Rev Neurol,
10(6), 313-314.
Author URL.
Corbett A, Burns A, Ballard C (2014). Don't use antipsychotics routinely to treat agitation and aggression in people with dementia.
BMJ,
349 Author URL.
Ballard C, Aarsland D, Francis P, Corbett A (2014). Erratum to: Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: Pathophysiology, clinical features, and pharmacological management (Drugs Aging (2013) 30, (603-611) DOI: 10.1007/s40266-013-0092-x). Drugs and Aging, 31(8).
Testad I, Corbett A, Aarsland D, Lexow KO, Fossey J, Woods B, Ballard C (2014). Erratum: the value of personalized psychosocial interventions to address behavioral and psychological symptoms in people with dementia living in care home settings: a systematic review (International Psychogeriatrics (2014) DOI; 10.1017/S1041610214000131)). International Psychogeriatrics, 26(7).
Sandvik RK, Selbaek G, Seifert R, Aarsland D, Ballard C, Corbett A, Husebo BS (2014). Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: a cluster randomized trial.
Eur J Pain,
18(10), 1490-1500.
Abstract:
Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: a cluster randomized trial.
BACKGROUND: Pain is frequent and distressing in people with dementia, but no randomized controlled trials have evaluated the effect of analgesic treatment on pain intensity as a key outcome. METHODS: Three hundred fifty-two people with dementia and significant agitation from 60 nursing home units were included in this study. These units, representing 18 nursing homes in western Norway, were randomized to a stepwise protocol of treating pain (SPTP) or usual care. The SPTP group received acetaminophen, morphine, buprenorphine transdermal patch and pregabalin for 8 weeks, with a 4-week washout period. Medications were governed by the SPTP and each participant's existing prescriptions. We obtained pain intensity scores from 327 patients (intervention n = 164, control n = 163) at five time points assessed by the primary outcome measure, Mobilization-Observation-Behaviour-Intensity-Dementia-2 (MOBID-2) Pain Scale. The secondary outcome was activities of daily living (ADL). We used a linear intercept mixed model in a two-way repeated measures configuration to assess change over time and between groups. RESULTS: the SPTP conferred significant benefit in MOBID-2 scores compared with the control group [average treatment effect (ATE) -1.388; p < 0.001] at week 8, and MOBID-2 scores worsened during the washout period (ATE = -0.701; p = 0.022). Examining different analgesic treatments, benefit was conferred to patients receiving acetaminophen compared with the controls at week 2 (ATE = -0.663; p = 0.010), continuing to increase until week 8 (ATE = -1.297; p < 0.001). Although there were no overall improvements in ADL, an increase was seen in the group receiving acetaminophen (ATE = +1.0; p = 0.022). CONCLUSION: Pain medication significantly improved pain in the intervention group, with indications that acetaminophen also improved ADL function.
Abstract.
Author URL.
Creese B, Ballard C, Corbett A (2014). Influence of the Tau Haplotype on Progression and Treatment Response of Neuropsychiatric Symptoms in People with Alzheimer's Disease.
Abstract:
Influence of the Tau Haplotype on Progression and Treatment Response of Neuropsychiatric Symptoms in People with Alzheimer's Disease
Objective: to determine the role of the tau haplotype in progression and treatment response of neuropsychiatric symptoms in Alzheimer’s Disease Background: Neuropsychiatric symptoms are a distressing a common symptom experienced by people with Alzheimer’s Disease. Emerging evidence indicates the role of genetics in the development of these symptoms. These include the H1c variant of the H1 extended tau haplotype of the MAPT gene which is thought to be associated with greater accumulation of neurofibrillary tangles (NFT) although these data are very preliminary. The potential differential response of the tau haplotypes to treatment has not been examined. Methods: DNA samples were provided by 95 people with AD as part of two clinical trial cohorts (MAIN-AD and MAGD) where participants received memantine or an alternative medication. Samples were genotyped for the H1/H2 haplotype and neuropsychiatric symptoms measured through the Neuropsychiatric Inventory. A regression model was created to account for variables, treatment arm and haplotype, including interaction between treatment and haplotype. Results: Analysis indicated a greater likelihood of worsening of delusions in people with at least one H2 allele (χ2=4.9, df=2, p=0.026; OR: 4.6). Comparison of treatment groups highlighted a significantly better outcome of neuropsychiatric symptoms following treatment with antipsychotics in comparison to memantine in people carrying at least one H2 allele (Mean change in total NPI score: 9.99 vs -6.62; F(1,14)=4.95, p=0.04). There was no difference in treatment response in people with the H1 haplotype (Mean change in total NPI score: 1.72 vs 4.83; F(1,39) =0.38, p=0.5). Conclusions: in addition to suggesting a key role for tau pathology in psychosis this study raises potential implications for treatment decisions. The data suggest that the tau haplotype could be used to identify individuals who are genetically predetermined to experience more enduring neuropsychiatric symptoms that are more likely to respond to antipsychotic treatment.
Abstract.
Broadstock M, Ballard C, Corbett A (2014). Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies.
Expert Opin Pharmacother,
15(13), 1797-1810.
Abstract:
Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies.
INTRODUCTION: Alzheimer's disease (AD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) together account for the vast majority of individuals with dementia. Approximately 35 million people worldwide are affected with this condition, and despite decades of research, effective therapies that slow or reverse disease progression have not yet been developed. The recent failure of several large-scale clinical trials is beginning to challenge the magnitude of focus on amyloid-related therapies for AD, and newer drug targets that have shown promise in the laboratory are being investigated in clinical trials. AREAS COVERED: This review summarises the current understanding of the underlying biology of AD, PDD and DLB and outlines the most recent drug candidates in advanced clinical trials. EXPERT OPINION: the lack of success in drug discovery for disease-modifying therapies for AD, PDD and DLB can be attributed to limitations in the design of clinical trials and the narrow focus of molecular targets for treatment. New avenues for drug discovery including repositioning and novel target identification may now provide opportunities for success, provided a critical mass of clinical trials is achieved through increased investment.
Abstract.
Author URL.
Corbett A, Smith J, Ballard C (2014). New and emerging treatments for Alzheimer’s disease. Expert Review of Neurotherapeutics, 12(5), 535-543.
Broadstock M, Ballard C, Corbett A (2014). Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease.
Expert Rev Clin Pharmacol,
7(6), 779-786.
Abstract:
Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease.
Parkinson's disease (PD) affects 10 million people worldwide. Half will develop psychosis, the majority experiencing hallucinations rather than delusions. Emergence of psychosis increases the likelihood of institutionalization and mortality. Where pharmacological treatment is warranted, options are limited. Most currently licensed atypical antipsychotics are ineffective or worsen motor symptoms in people with PD. This review of provides an overview of the current landscape of treatments and the opportunities in emerging research. Clozapine is the only licensed antipsychotic with proven efficacy, although the associated side effects limit its use. With recent advances in understanding the role of serotonin, rational drug design approaches have delivered a novel pharmacological treatment with recently proven efficacy in clinical trials of people with PD and psychosis. Pimavanserin represents an important addition to treatment.
Abstract.
Author URL.
Lichtner V, Dowding D, Esterhuizen P, Closs SJ, Long AF, Corbett A, Briggs M (2014). Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.
BMC Geriatr,
14Abstract:
Pain assessment for people with dementia: a systematic review of systematic reviews of pain assessment tools.
BACKGROUND: There is evidence of under-detection and poor management of pain in patients with dementia, in both long-term and acute care. Accurate assessment of pain in people with dementia is challenging and pain assessment tools have received considerable attention over the years, with an increasing number of tools made available. Systematic reviews on the evidence of their validity and utility mostly compare different sets of tools. This review of systematic reviews analyses and summarises evidence concerning the psychometric properties and clinical utility of pain assessment tools in adults with dementia or cognitive impairment. METHODS: We searched for systematic reviews of pain assessment tools providing evidence of reliability, validity and clinical utility. Two reviewers independently assessed each review and extracted data from them, with a third reviewer mediating when consensus was not reached. Analysis of the data was carried out collaboratively. The reviews were synthesised using a narrative synthesis approach. RESULTS: We retrieved 441 potentially eligible reviews, 23 met the criteria for inclusion and 8 provided data for extraction. Each review evaluated between 8 and 13 tools, in aggregate providing evidence on a total of 28 tools. The quality of the reviews varied and the reporting often lacked sufficient methodological detail for quality assessment. The 28 tools appear to have been studied in a variety of settings and with varied types of patients. The reviews identified several methodological limitations across the original studies. The lack of a 'gold standard' significantly hinders the evaluation of tools' validity. Most importantly, the samples were small providing limited evidence for use of any of the tools across settings or populations. CONCLUSIONS: There are a considerable number of pain assessment tools available for use with the elderly cognitive impaired population. However there is limited evidence about their reliability, validity and clinical utility. On the basis of this review no one tool can be recommended given the existing evidence.
Abstract.
Author URL.
Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C (2014). Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial.
Lancet,
383(9916), 533-540.
Abstract:
Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial.
BACKGROUND: Parkinson's disease psychosis, which includes hallucinations and delusions, is frequent and debilitating in people with Parkinson's disease. We aimed to assess safety and efficacy of pimavanserin, a selective serotonin 5-HT2A inverse agonist, in this population. METHODS: in our 6 week, randomised, double-blind, placebo-controlled study, we enrolled adults (aged ≥40 years) with Parkinson's disease psychosis. Antipsychotic treatments were not permitted during the study, but controlled antiparkinsonian medication or deep brain stimulation was allowed. Eligible participants entered a 2 week non-pharmacological lead-in phase to limit the placebo response, after which they were randomly allocated (1:1) to receive pimavanserin 40 mg per day or matched placebo. The primary outcome was antipsychotic benefit as assessed by central, independent raters with the Parkinson's disease-adapted scale for assessment of positive symptoms (SAPS-PD) in all patients who received at least one dose of study drug and had a SAPS assessment at baseline and at least one follow-up. We assessed safety and tolerability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01174004. FINDINGS: Between Aug 11, 2010, and Aug 29, 2012, we randomly allocated 199 patients to treatment groups. For 90 recipients of placebo and 95 recipients of pimavanserin included in the primary analysis, pimavanserin was associated with a -5·79 decrease in SAPS-PD scores compared with -2·73 for placebo (difference -3·06, 95% CI -4·91 to -1·20; p=0·001; Cohen's d 0·50). Ten patients in the pimavanserin group discontinued because of an adverse event (four due to psychotic disorder or hallucination within 10 days of start of the study drug) compared with two in the placebo group. Overall, pimavanserin was well tolerated with no significant safety concerns or worsening of motor function. INTERPRETATION: Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist. The trial design used in this study to manage placebo response could have applicability to other studies in neuropsychiatric disease. FUNDING: ACADIA Pharmaceuticals.
Abstract.
Author URL.
Ballard C, Corbett A, Howard R (2014). Prescription of antipsychotics in people with dementia.
Br J Psychiatry,
205(1), 4-5.
Author URL.
Ballard C, Francis P, Corbett A (2014). Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies - ADDENDUM.
Int Psychogeriatr Author URL.
Creese B, Corbett A, Jones E, Fox C, Ballard C (2014). Role of the Extended MAPT Haplotype in the Worsening of Psychotic Symptoms and Treatment Response in Alzheimer Disease. Journal of the American Medical Directors Association, 15(12), 934-937.
Ballard C, Corbett A (2014). Screening for dementia: an opportunity for debate. Expert Review of Neurotherapeutics, 11(10), 1347-1349.
Ballard C, Mills R, Williams H, Corbett A, Cummings J (2014). TREATMENT OF PSYCHOSIS IN PARKINSON'S DISEASE AND PARKINSON'S DISEASE DEMENTIA.
Author URL.
Fossey J, Masson S, Stafford J, Lawrence V, Corbett A, Ballard C (2014). The disconnect between evidence and practice: a systematic review of person-centred interventions and training manuals for care home staff working with people with dementia.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY,
29(8), 797-807.
Author URL.
Corbett A, Husebo BS, Achterberg WP, Aarsland D, Erdal A, Flo E (2014). The importance of pain management in older people with dementia.
Br Med Bull,
111(1), 139-148.
Abstract:
The importance of pain management in older people with dementia.
INTRODUCTION: Pain is common in people with dementia, representing a critical aspect of treatment and care. However, there remain considerable gaps in evidence to support pain assessment and treatment. SOURCES OF DATA: an updated literature search focussing on systematic reviews and randomized controlled trials. AREAS OF AGREEMENT: There are key areas of consistency around the prevalence, causes and current treatment trends for pain in dementia, the impact of untreated pain and the need for an accurate, fully validated assessment tool. AREAS OF CONTROVERSY: Accurate assessment due to inherent issues in dementia is a critical challenge. There is also a lack of evidence around alternative treatment options. GROWING POINTS: New pain predictors are being identified, including physical function, depression and specific pain types, which should inform assessment methodology. AREAS TIMELY FOR DEVELOPING RESEARCH: Future research should focus on developing integrated pain management approaches with optimized assessment and evidence-based treatment guidance.
Abstract.
Author URL.
Testad I, Corbett A, Aarsland D, Lexow KO, Fossey J, Woods B, Ballard C (2014). The value of personalized psychosocial interventions to address behavioral and psychological symptoms in people with dementia living in care home settings: a systematic review.
INTERNATIONAL PSYCHOGERIATRICS,
26(7), 1083-1098.
Author URL.
Corbett A, Ballard C (2014). The value of vitamin E as a treatment for Alzheimer's disease remains unproven despite functional improvement, due to a lack of established effect on cognition or other outcomes from RCTs. Evidence Based Medicine, 19(4), 140-140.
2013
Ballard C, Corbett A (2013). Agitation and aggression in people with Alzheimer's disease. Current Opinion in Psychiatry, 26(3), 252-259.
Corbett A, Nunez K, Thomas A (2013). Coping with dementia in care homes. Maturitas, 76(1), 3-4.
Corbett A, Husebo B, Malcangio M, Staniland A, Cohen-Mansfield J, Aarsland D, Ballard C (2013). Correction: Assessment and treatment of pain in people with dementia. Nature Reviews Neurology, 9(7), 358-358.
Ballard C, Jones E, Gauge N, Aarsland D, Nilsen OB, Saxby BK, Lowery D, Corbett A, Wesnes K, Katsaiti E, et al (2013). Correction: Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PLoS ONE, 8(9).
Corbett A, Williams G, Ballard C (2013). Drug Repositioning: an Opportunity to Develop Novel Treatments for Alzheimer’s Disease. Pharmaceuticals, 6(10), 1304-1321.
Corbett A, Smith J, Ballard C (2013). Erratum: New and emerging treatments for Alzheimer's disease (Expert Review of Neurotherapeutics (2012) 12:5 (533-543) DOI: 10.1586/ern.12.43). Expert Review of Neurotherapeutics, 13(7).
Corbett A, Smith J, Ballard C (2013). Erratum: New and emerging treatments for Alzheimer's disease (Expert Review of Neurotherapeutics (2012) 12:5 (535-543)). Expert Review of Neurotherapeutics, 13(6).
Clare L, Bayer A, Burns A, Corbett A, Jones R, Knapp M, Kopelman M, Kudlicka A, Leroi I, Oyebode J, et al (2013). Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT).
Trials,
14Abstract:
Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT).
BACKGROUND: Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer's disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. METHODS/DESIGN: in this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. DISCUSSION: If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion.
Abstract.
Author URL.
Corbett A, Ballard C (2013). Is a potential Alzheimer's therapy already in use for other conditions? can medications for hypertension, diabetes and acne help with the symptoms?. Expert Opinion on Investigational Drugs, 22(8), 941-943.
Ballard C, Aarsland D, Francis P, Corbett A (2013). Neuropsychiatric Symptoms in Patients with Dementias Associated with Cortical Lewy Bodies: Pathophysiology, Clinical Features, and Pharmacological Management. Drugs & Aging, 30(8), 603-611.
Corbett A, Smith J, Ballard C (2013). New and emerging treatments for Alzheimer's disease (vol 12, pg 535, 2012).
EXPERT REVIEW OF NEUROTHERAPEUTICS,
13(7), 871-871.
Author URL.
Corbett A, Smith J, Ballard C (2013). New and emerging treatments for Alzheimer's disease (vol 12, pg 535, 2012).
EXPERT REVIEW OF NEUROTHERAPEUTICS,
13(6), 734-734.
Author URL.
Achterberg W, Pieper MJC, van Dalen-Kok AH, de Waal MWM, Husebo BS, Lautenbacher S, Kunz M, Scherder EJA, Corbett A (2013). Pain management in patients with dementia. Clinical Interventions in Aging, 1471-1471.
Ballard C, Corbett A (2013). Randomised controlled trial: a small proportion of people with dementia and neuropsychiatric symptoms experience clinically significant worsening when antidepressants are discontinued (Evidence-Based Medicine (2013) 18, (27-28)). Evidence-Based Medicine, 18(3).
Ballard C, Francis P, Corbett A (2013). Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies.
International Psychogeriatrics,
25(5), 687-689.
Abstract:
Randomized controlled trial of mibampator for behavioral and psychological symptoms of dementia: comments on the trial and thoughts for future studies
Behavioral and psychological symptoms of dementia (BPSD) frequently arise in people with Alzheimer's disease (AD) and other dementias. They cause significant distress and confer risk to the person and others, in addition to presenting a complex clinical challenge for treatment (Ballard et al. 2009b). There is good evidence for the value of first-line management strategies such as psychological interventions and treatment of concurrent medical conditions, particularly pain, which are known to be effective (Ballard et al. 2009b). However, there are limited pharmacological treatment options for severe aggression, which causes significant risk, and for other severe BPSD which do not respond to first-line approaches. The only pharmacological intervention with an adequate evidence base is the prescription of atypical antipsychotics, where 18 placebo-controlled trials have evaluated the effect of treatment over 6–12 weeks. The literature indicates modest but significant benefits in the treatment of aggression and psychosis with risperidone and aripiprazole (Cohen's d standardized effect size of 0.2), uncertain benefits with olanzapine, and no benefits with quetiapine (Ballard and Howard, 2006; Schneider et al. 2006a; Ballard et al. 2009b; Corbett et al. 2012). Unfortunately, the benefits of longer term prescribing are more limited (Schneider et al. 2006b; Ballard et al. 2008) and there have been increasing concerns regarding the potential for serious adverse outcomes, including accelerated cognitive decline, stroke, and death (Schneider et al. 2006b; Ballard et al. 2009a). There is therefore an urgent imperative to identify more effective pharmacological treatments for severe BPSD which have a better safety profile, particularly for long-term treatment and prophylaxis. Despite this urgency, there has been very little effort toward developing or evaluating potential novel therapies for the treatment of key symptoms such as aggression, psychosis, restlessness, and apathy.
Abstract.
Corbett A, Francis P, Ballard C (2013). Safety and efficacy of memantine extended-release in the management of alzheimer's disease.
Clinical Medicine Insights: Therapeutics,
5, 95-102.
Abstract:
Safety and efficacy of memantine extended-release in the management of alzheimer's disease
Alzheimer's disease (AD) affects the majority of the 35 million people with dementia worldwide. Four pharmacological treatment options are available for this patient group, of which memantine is licensed for treatment of people with moderate to severe stages of the condition. Memantine acts through its function as an NMDA-glutamate receptor blocker and has an established safety profile. The evidence supporting its efficacy in people with AD includes a number of large randomized clinical trials showing benefit to cognition, function, and overall clinical outcome. Additional favorable health economics analyses have confirmed the clinical and cost-effectiveness of this drug. More recently an extended-release formulation has been developed. This review outlines the key evidence base supporting memantine as a treatment for moderate to severe AD, in addition to discussing the conditions under which it may provide additional value in combination with other drugs. The review also discusses the use of memantine to address behavioral and psychological symptoms of dementia (BPSD) arising in people with AD and the limited evidence around its use in AD in people with Down's syndrome. Finally the review considers the potential value of the extended release formulation in AD. © the author(s), publisher and licensee Libertas Academica Ltd.
Abstract.
2012
Ballard C, Corbett A (2012). A small proportion of people with dementia and neuropsychiatric symptoms experience clinically significant worsening when antidepressants are discontinued. Evidence Based Medicine, 18(1), 27-28.
Corbett A, Ballard C (2012). Antipsychotics and Mortality in Dementia. American Journal of Psychiatry, 169(1), 7-9.
Corbett A, Husebo B, Malcangio M, Staniland A, Cohen-Mansfield J, Aarsland D, Ballard C (2012). Assessment and treatment of pain in people with dementia.
Nature Reviews Neurology,
8(5), 264-274.
Abstract:
Assessment and treatment of pain in people with dementia
Many elderly people experience pain and regularly take analgesic medication. Pain is also frequent in people with dementia, particularly those with severe disease. As no robust clinical guidelines are available for the treatment of pain in the context of dementia, the risk of inadequate treatment in individuals with this condition is high. Furthermore, our understanding of the aetiology of pain and the potential role of dementia-associated neuropathology in pain is limited. These issues are important in the clinical management of individuals with dementia, as untreated pain is a major contributor to reduced quality of life and disability, and can lead to increased behavioural and psychological symptoms. Assessment scales to identify pain in people with dementia have been highlighted in recent studies, but there is little evidence for consistency between these tools. Numerous studies have evaluated various approaches for the treatment of pain, including stepped-care protocols and/or administration of paracetamol and opioid medications. In this Review, we summarize the best-available evidence regarding the aetiology, assessment and treatment of pain in people with dementia. Further validation of assessment tools and large-scale trials of treatment approaches in people with dementia are needed to improve clinical guidance for the treatment of pain in these individuals © 2012 Macmillan Publishers Limited. All rights reserved.
Abstract.
(2012). Correction: Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PloS one, 7(9).
Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, et al (2012). Drug repositioning for Alzheimer's disease. Nature Reviews Drug Discovery, 11(11), 833-846.
Ballard C, Corbett A (2012). Management of agitation and aggression: Controversies and possible solutions. In (Ed) Advances in Alzheimer's Disease Management, 69-79.
Hanney M, Prasher V, Williams N, Jones EL, Aarsland D, Corbett A, Lawrence D, Yu L-M, Tyrer S, Francis PT, et al (2012). Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.
LANCET,
379(9815), 528-536.
Author URL.
Corbett A, Ballard C (2012). New and emerging treatments for Alzheimer's disease.
Expert Opin Emerg Drugs,
17(2), 147-156.
Abstract:
New and emerging treatments for Alzheimer's disease.
INTRODUCTION: Alzheimer's disease and other dementias represent a significant and increasing clinical challenge. Dementia is also associated with a substantial economic cost and burden to health service provision. Existing treatments slow the progression of symptoms of the disease, but their efficacy does not extend to all patients and is not sustained beyond an average of 6 months. It is, therefore, critical to address the current lack of effective treatments to target the underlying pathology and disease process in Alzheimer's disease. AREAS COVERED: This review aims to highlight the main areas of new therapeutic development and discuss some of the main therapies currently being evaluated in clinical trials. Despite a number of promising rationales for therapeutic treatments in Alzheimer's disease, very few of these avenues have been developed beyond preclinical studies. The predominant focus of the current article is on treatments currently in Phase II and Phase III clinical trials, but some other promising areas of development are also discussed. There are currently only three therapeutics being investigated in Phase III clinical trials. This emphasizes the substantial caution and underinvestment in treatment development in this area. EXPERT OPINION: There is a distinct lack of novel approaches in the pipeline, and whether there is a new disease-modifying therapy for Alzheimer's disease in the next 5 years almost entirely depends on the success of currently ongoing immunotherapy studies. Importantly, there is potential benefit in exploring existing licensed treatments alongside novel drug development to increase the focus on novel targets within this time frame.
Abstract.
Author URL.
Ballard C, Corbett A (2012). New guidelines on disorders associated with dementia. Nature Reviews Neurology, 8(12), 663-664.
Ballard C, Jones E, Gauge N, Aarsland D, Nilsen OB, Saxby BK, Lowery D, Corbett A, Wesnes K, Katsaiti E, et al (2012). Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PLoS ONE, 7(6), e37410-e37410.
Corbett A, Smith J, Creese B, Ballard C (2012). Treatment of Behavioral and Psychological Symptoms of Alzheimer’s Disease. Current Treatment Options in Neurology, 14(2), 113-125.
2011
Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011). Alzheimer's disease.
LANCET,
377(9770), 1019-1031.
Author URL.
Creese B, Ballard C, Corbett A, Aarsland D (2011). Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality. Expert Opinion on Drug Safety, 10, 35-43.
Ballard C, Corbett A, Jones EL (2011). Dementia: challenges and promising developments. The Lancet Neurology, 10(1), 7-9.
Ballard C, Corbett A, Pickett J (2011). Depression and dementia.
Ment Health Today, 23-25.
Author URL.
Talà A, Monaco C, Nagorska K, Exley RM, Corbett A, Zychlinsky A, Alifano P, Tang CM (2011). Glutamate utilization promotes meningococcal survival in vivo through avoidance of the neutrophil oxidative burst. Molecular Microbiology, 81(5), 1330-1342.
Corbett A, Ballard C (2011). Information provision services in dementia care. International Journal of Older People Nursing, 6(3), 217-226.
Ballard C, Khan Z, Clack H, Corbett A (2011). Nonpharmacological treatment of Alzheimer disease.
Can J Psychiatry,
56(10), 589-595.
Abstract:
Nonpharmacological treatment of Alzheimer disease.
OBJECTIVE: to review the key nonpharmacological treatment approaches to the cognitive and functional symptoms of Alzheimer disease (AD). METHODS: We searched and critically analyzed the most recent relevant literature pertaining to the nonpharmacological treatment of AD. RESULTS: There is evidence from a modest number of well-conducted randomized controlled trials (RCTs) that various nonpharmacological approaches, including cognitive training, cognitive rehabilitation, and cognitive stimulation therapy (CST), confer modest but significant benefits in the treatment of cognitive symptoms in people with AD, and that there may be additive benefits in combination with cholinesterase inhibitor therapy. Cognitive rehabilitation also appears to result in functional benefits in AD. The modest number of RCTs focusing on cognitive training in AD is consistent with the results of larger cognitive training trials in healthy older people. however, there is no convincing evidence of any benefits associated with brain training games. CONCLUSION: an emerging evidence base indicates that different approaches to cognitive training and cognitive stimulation in people with AD confer modest but significant benefits. The best evidence base is for CST, although this approach is labour-intensive, and requires further evaluation of cost-effectiveness. There is currently no evidence that brain training games provide any significant benefit to people with AD.
Abstract.
Author URL.
Corbett A, Stevens J, Aarsland D, Day S, Moniz-Cook E, Woods R, Brooker D, Ballard C (2011). Systematic review of services providing information and/or advice to people with dementia and/or their caregivers. International Journal of Geriatric Psychiatry, 27(6), 628-636.
Ballard C, Smith J, Husebo B, Aarsland D, Corbett A (2011). The role of pain treatment in managing the behavioural and psychological symptoms of dementia (BPSD).
Int J Palliat Nurs,
17(9), 420-424.
Author URL.
Ballard C, Kahn Z, Corbett A (2011). Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
Drugs Aging,
28(10), 769-777.
Abstract:
Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) account for 10-15% of late onset dementias. Key treatment targets include cognitive and functional impairments, neuropsychiatric symptoms including intense and persistent visual hallucinations, and parkinsonism. Six-month, placebo-controlled randomized controlled trials (RCTs) of the cholinesterase inhibitor rivastigmine have indicated modest but significant benefits in cognition, function, global outcome and neuropsychiatric symptoms in both PDD and DLB. The evidence base for other cholinesterase inhibitors from RCTs is inconclusive. More recent RCTs with memantine in PDD/DLB patients indicate a benefit with regard to global outcome, with some suggestion of a specific benefit with respect to sleep disturbance. Given the risk of severe antipsychotic sensitivity reactions, antipsychotics should be avoided. A significant proportion of PDD/DLB patients are responsive to levodopa, but care needs to be taken with anti-parkinsonian treatments because of their potential propensity to exacerbate neuropsychiatric symptoms, particularly hallucinations.
Abstract.
Author URL.
2010
Ballard C, Corbett A (2010). Management of neuropsychiatric symptoms in people with dementia.
CNS Drugs,
24(9), 729-739.
Abstract:
Management of neuropsychiatric symptoms in people with dementia.
Neuropsychiatric symptoms are frequent and troublesome in people with dementia and present a major treatment challenge for clinicians. Most good practice guidelines suggest non-pharmacological treatments as the first-line therapy and there is emerging evidence, including randomized controlled trials, that a variety of psychological and training interventions, including social interaction and person-centred care training, are effective. There is evidence from meta-analyses that some atypical antipsychotic drugs, specifically risperidone and aripiprazole, confer benefit in the treatment of aggression in people with Alzheimer's disease over a period of up to 12 weeks. However, these benefits have to be considered in the context of significant adverse events, including extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In addition, the limited evidence available does not indicate ongoing treatment benefits over longer periods of therapy. The evidence is limited for other pharmacological treatment approaches, but the best evidence is probably for carbamazepine, memantine and citalopram. There is very limited evidence for any therapies in non-Alzheimer dementias. In conclusion, it is important in most situations to limit the use of antipsychotic medication to short-term treatment (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non-pharmacological therapies offer a viable and effective alternative in many situations. Adequately powered randomized controlled trials for the treatment of clinically significant agitation are urgently needed to explore alternative pharmacological therapies.
Abstract.
Author URL.
2009
Ballard C, Corbett A, Chitramohan R, Aarsland D (2009). Management of agitation and aggression associated with Alzheimerʼs disease: controversies and possible solutions. Current Opinion in Psychiatry, 22(6), 532-540.
2007
Carpenter EP, Corbett A, Thomson H, Adacha J, Jensen K, Bergeron J, Kasampalidis I, Exley R, Winterbotham M, Tang C, et al (2007). AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis. The EMBO Journal, 26(5), 1363-1372.
2004
Corbett A, Exley R, Bourdoulous S, Tang CM (2004). Interactions between <i>Neisseria meningitidis</i> and human cells that promote colonisation and disease.
Expert Reviews in Molecular Medicine,
6(14), 1-14.
Abstract:
Interactions between Neisseria meningitidis and human cells that promote colonisation and disease
Neisseria meningitidis is the leading cause of bacterial meningitis, a potentially fatal condition that particularly affects children. Multiple steps are involved during the pathogenesis of infection, including the colonisation of healthy individuals and invasion of the bacterium into the cerebrospinal fluid. The bacterium is capable of adhering to, and entering into, a range of human cell types, which facilitates its ability to cause disease. This article summarises the molecular basis of host–pathogen interactions at the cellular level during meningococcal carriage and disease.
Abstract.
