Publications by category
Journal articles
Creese B (In Press). A Data-Driven Examination of Apathy and Depressive Symptoms in Dementia with Independent Replication. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Smith S, Griffiths AW, Creese B, Sass C, Surr C (In Press). A biopsychosocial interpretation of the Neuropsychiatric Inventory-Nursing Home (NH): reconceptualising psychiatric symptom attributions. BJPsych Open
Creese B (In Press). A longitudinal study of late-life psychosis and incident dementia and the potential effects of race and cognition. Nature Mental Health
Creese B, Vassos E, Bergh S, Athanasiu L, Johar I, Rongve A, Medbøen IT, Da Silva MV, Aakhus E, Andersen F, et al (In Press). Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer’s disease: meta-analysis of 11 cohort studies.
Abstract:
Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer’s disease: meta-analysis of 11 cohort studies
AbstractBackgroundPsychosis (delusions and hallucinations) is common in Alzheimer’s disease (AD) and associated with worse clinical outcomes including accelerated cognitive decline and shorter time to nursing home admission. Atypical antipsychotics have limited efficacy which, along with emerging genomic research, suggests some overlapping mechanisms with other disorders characterized by psychosis, like schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with psychotic symptoms in AD.MethodsSchizophrenia PRS was calculated using Psychiatric Genomics Consortium data at 10 GWAS p-value thresholds (PT) in 3,173 AD cases from 11 cohort studies. Association between PRS and AD psychosis status was tested by logistic regression in each cohort individually and the results meta-analyzed.ResultsThe schizophrenia PRS was associated with psychosis in AD at an optimumPTof the strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.17-fold increased risk (95% CI: 1.07-1.3; p=0.001).ConclusionThese new findings point towards psychosis in AD – and particularly delusions – sharing some genetic liability with schizophrenia, and support a transdiagnostic view of psychotic symptoms across the lifespan.
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Creese B, Ballard C (In Press). Cost-effectiveness of Dementia Care Mapping in care home settings – Evaluation of a randomised controlled trial. Applied Health Economics and Health Policy
Surr C, Holloway I, Walwyn REA, Grifiths AW, Meads D, Martin A, Kelley R, Ballard C, Fossey J, Burnley N, et al (In Press). Effectiveness of Dementia Care Mapping™ to reduce agitation in care home residents with dementia: an open-cohort cluster randomised controlled trial. Aging and Mental Health
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
Wolfova K, Creese B, Aarsland D, Ismail Z, Corbett A, Ballard C, Hampshire A, Cermakova P (In Press). Gender/sex differences in the association of mild behavioral impairment with cognitive aging. Journal of Alzheimer's Disease
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
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I, Moreno-Grau S, Tárraga L, et al (In Press). Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease.
Abstract:
Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease
AbstractPsychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD+P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.
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Wang J, Spencer A, Hulme C, Corbett A, Khan Z, Vasconcelos Da Silva M, O'Dwyer S, Wright N, Testad I, Ballard C, et al (In Press). Healthcare utilisation and physical activities for older adults with comorbidities in the UK during COVID-19. Health and Social Care in the Community
Wang J, Spencer A, Hulme C, Khan Z, Vasconcelos Da Silva M, O'Dwyer S, Wright N, Testad I, Ballard C, Creese B, et al (In Press). Healthcare utilisation, physical activity and mental health during COVID-19 lockdown: an interrupted time-series analysis of older adults in England. European Journal of Ageing
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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Creese B, Arathimos R, Aarsland D, Ballard C, Brooker H, Hampshire A, Corbett A, Ismail Z (In Press). Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: modification by genetic risk for Alzheimer’s disease. Alzheimer's and Dementia: Translational Research and Clinical Interventions
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 and/or irritable episode symptoms in two 1 population-based cohorts. British Journal of Psychiatry
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.
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Lennon M, Brooker H, Creese B, Thayanandan T, Rigney G, Aarsland D, Hampshire A, Ballard C, Corbett A, Raymont V, et al (In Press). Lifetime TBI and cognitive domain deficits in late life: the PROTECT-TBI cohort study. Journal of Neurotrauma
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
Creese B, Ismail Z (In Press). Mild Behavioral Impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease.
Alzheimer's Research and TherapyAbstract:
Mild Behavioral Impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease
Background: Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was established to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease.
Main: MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10-15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people.
Conclusion: the emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease.
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Daunt P, Ballard C, Creese B, Davidson G, Hardy J, Oshota O, Pither RJ, Gibson AM (In Press). Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease. The journal of prevention of Alzheimer's disease
Pishva SE, Creese B, Smith A, Ballard C, Mill J, Lunnon K (In Press). Psychosis-associated DNA methylomic variation in Alzheimer’s disease cortex. Neurobiology of Aging
Creese B, Ballard C (In Press). Revisiting criteria for psychosis in Alzheimer’s disease and related dementias- towards better phenotypic classification and biomarker research. Journal of Alzheimer's Disease
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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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
Griffiths A, Albertyn C, Burnley N, Creese BA, Walwyn R, Holloway I, Safarikova J, Surr C (In Press). Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) Tool. International Psychogeriatrics
Malekizadeh Y, Williams G, Kelson M, Whitfield D, Mill J, Collier D, Ballard C, Jeffries A, Creese B (In Press). Whole transcriptome in-silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects. Alzheimer's and Dementia: Translational Research and Clinical Interventions
Rogowska M, Thornton M, Creese B, Velayudhan L, Aarsland D, Ballard C, Tsamakis K, Stewart R, Mueller C (2023). Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: a 2011-2022 Update.
Drugs Aging,
40(1), 21-32.
Abstract:
Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: a 2011-2022 Update.
Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.
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Munir A, Ghahremani M, Smith EE, Creese B, Fischer CE, Ismail Z (2023). Late life onset of persistent psychosis and incident dementia: risk stratification by baseline cognitive status. Alzheimer's & Dementia, 19(S4).
Packer A, Corbett A, Arathimos R, Ballard C, Aarsland D, Hampshire A, Dima D, Creese B, Malanchini M, Powell TR, et al (2023). Limited evidence of a shared genetic relationship between C-reactive protein levels and cognitive function in older UK adults of European ancestry. Frontiers in Dementia, 2
Ghahremani M, Chen H, Creese B, Goodarzi Z, Smith EE, Ismail Z (2023). Longitudinal association between exposure to vitamin D supplementation and incident dementia – a study of dementia‐free older adults. Alzheimer's & Dementia, 19(S8).
Ismail Z, Leon R, Creese B, Ballard C, Robert P, Smith EE (2023). Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO.
Molecular Neurodegeneration,
18(1).
Abstract:
Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO
Abstract
. Background
. Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally.
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. Methods
. Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions).
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. Results
. of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p < 0.001), and t-tau/Aβ42 (p = 0.001). NPSnotMBI was associated only with lower Aβ42/40 (p = 0.045). LMEs revealed a similar 4-year AD-specific biomarker profile for MBI, with NPSnotMBI associated only with higher t-tau. MBI had a greater rate of incident dementia (HR [95%CI], 3.50 [1.99–6.17; p < 0.001). NPSnotMBI did not differ from noNPS (HR 0.96 [0.49–1.89]; p = 0.916). In MEMENTO, MBI demonstrated a similar magnitude and direction of effect for all biomarkers, but with a greater reduction in Aβ40. HR for incident dementia was 3.93 (p = 0.004) in MBI, and 1.83 (p = 0.266) in NPSnotMBI. of MBI progressors to dementia, 81% developed AD dementia.
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. Conclusions
. These findings support a biological basis for NPS that meet MBI criteria, the continued inclusion of MBI in NIA-AA ATN clinical staging, and the utility of MBI criteria to improve identification of patients for enrollment in disease-modifying drug trials or for clinical care.
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Albertyn CP, Johar I, Creese B, Young A, Carter B, Velayudhan L, Bhattacharyya S, Vasconcelos Da Silva M, Samsi K, Jafari H, et al (2023). Sativex® for the treatment of Agitation & Aggression in Alzheimer’s Dementia in UK nursing homes (STAND): Protocol for a feasibility randomised controlled trial. Health Open Research, 5
Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2023). Self-harm and Suicidality Experiences of Middle-Age and Older Adults with vs. Without High Autistic Traits.
J Autism Dev Disord,
53(8), 3034-3046.
Abstract:
Self-harm and Suicidality Experiences of Middle-Age and Older Adults with vs. Without High Autistic Traits.
Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours.
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Kouhsar MP, Creese B, Weymouth LS, Smith AR, Bergh S, Wedatilake Y, Selbæk G, Torkamani A, Mill J, Ballard CG, et al (2023). Transcription‐based drug repurposing in Alzheimer disease psychosis. Alzheimer's & Dementia, 19(S1).
Ghahremani M, Smith EE, Chen H-Y, Creese B, Goodarzi Z, Ismail Z (2023). Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status.
Alzheimers Dement (Amst),
15(1).
Abstract:
Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status.
INTRODUCTION: Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia-free persons from the National Alzheimer's Coordinating Center. METHODS: Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D-. Kaplan-Meier curves compared dementia-free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E (APOE) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. RESULTS: Across all formulations, vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55-0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. DISCUSSION: Vitamin D may be a potential agent for dementia prevention. HIGHLIGHTS: in a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset.Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure.Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment.Vitamin D effects were significantly greater in apolipoprotein E ε4 non-carriers versus carriers.Vitamin D has potential for dementia prevention, especially in the high-risk strata.
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Imm JL, Harvey J, Creese B, Chouliaras L, Dempster E, Ballard CG, O'Brien JT, Aarsland D, Mill J, Pishva E, et al (2022). A Role for Epigenetic Mechanisms in the Lewy Body Dementias. Alzheimer's & Dementia, 18(S3).
Weymouth LS, Kouhsar MP, Creese B, Bergh S, Wedatilake Y, Torkamani A, Smith AR, Selbaek G, Sweet R, Ballard CG, et al (2022). An Epigenome‐wide association study of psychosis in Alzheimer's disease dorsolateral prefrontal cortex. Alzheimer's & Dementia, 18(S4).
Harvey J, Smith AR, Weymouth LS, Smith RG, Hubbard L, Bresner K, Pishva E, Williams N, Lunnon K, Creese B, et al (2022). An epigenome wide association study of sub‐phenotypes in Parkinson’s disease. Alzheimer's & Dementia, 18(S4).
Singham T, Saunders R, Brooker H, Creese B, Aarsland D, Hampshire A, Ballard C, Corbett A, Desai R, Stott J, et al (2022). Are subtypes of affective symptoms differentially associated with change in cognition over time: a latent class analysis.
J Affect Disord,
309, 437-445.
Abstract:
Are subtypes of affective symptoms differentially associated with change in cognition over time: a latent class analysis.
BACKGROUND: in the absence of disease-modifying treatments, identifying potential psychosocial risk factors for dementia is paramount. Depression and anxiety have been identified as potential risk factors. Studies however have yielded mixed findings, lending possibility to the fact that potential constellations of co-occurring depression and anxiety symptoms may better explain the link between affective symptoms and cognitive decline. METHODS: Data from participants (aged 50 and above) of the PROTECT study was used. Latent Class Analysis (LCA) was conducted on 21,684 participants with baseline anxiety and depression measures. Multiple linear regressions models, using a subset of these participants (N = 6136) who had complete cognition data at baseline and at 2-year follow-up, were conducted to assess for associations between class membership and longitudinal changes in cognition. RESULTS: the LCA identified a 5-class solution: "No Symptoms", "Sleep", "Sleep and Worry", "Sleep and Anhedonia", and "Co-morbid Depression and Anxiety". Class membership was significantly associated with longitudinal change in cognition. Furthermore, this association differed across different cognitive measures. LIMITATIONS: Limitations included significant attrition and a generally healthy sample which may impact generalisability. CONCLUSIONS: Substantial heterogeneity in affective symptoms could explain previous inconsistent findings concerning the association between affective symptoms and cognition. Clinicians should not focus solely on total symptom scores on a single affective domain, but instead on the presence and patterns of symptoms (even if sub-clinical) on measures across multiple affective domains. Identifying particular subgroups that are at greater risk of poor cognitive outcomes may support targeted prevention work.
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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 (2022). Latent subtypes of manic and/or irritable episode symptoms in two population-based cohorts - ERRATUM.
Br J Psychiatry, 1-2.
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Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen L, Rutten BPF, Shireby G, Torkamani A, Creese B, et al (2022). Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.
NPJ Parkinsons Dis,
8(1).
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Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.
Cognitive impairment is a debilitating symptom in Parkinson's disease (PD). We aimed to establish an accurate multivariate machine learning (ML) model to predict cognitive outcome in newly diagnosed PD cases from the Parkinson's Progression Markers Initiative (PPMI). Annual cognitive assessments over an 8-year time span were used to define two cognitive outcomes of (i) cognitive impairment, and (ii) dementia conversion. Selected baseline variables were organized into three subsets of clinical, biofluid and genetic/epigenetic measures and tested using four different ML algorithms. Irrespective of the ML algorithm used, the models consisting of the clinical variables performed best and showed better prediction of cognitive impairment outcome over dementia conversion. We observed a marginal improvement in the prediction performance when clinical, biofluid, and epigenetic/genetic variables were all included in one model. Several cerebrospinal fluid measures and an epigenetic marker showed high predictive weighting in multiple models when included alongside clinical variables.
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Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen LMT, Rutten BPF, Shireby G, Torkamani A, Creese B, et al (2022). Machine learning‐based prediction of cognitive outcomes in de novo Parkinson's disease. Alzheimer's & Dementia, 18(S5).
Creese B, Lunnon K (2022). Neuropsychiatric symptoms in AD: the search for mechanisms. Nature Reviews Neurology, 18(11), 639-640.
Harvey J, Reijnders RA, Shireby G, Duits A, Köhler S, Creese B, Lunnon K, Pishva E (2022). Polygenic risk score association with cognitive decline in Parkinson’s Disease. Alzheimer's & Dementia, 18(S4).
Agüera-Ortiz L, Babulal GM, Bruneau M-A, Creese B, D’Antonio F, Fischer CE, Gatchel JR, Ismail Z, Kumar S, McGeown WJ, et al (2022). Psychosis as a Treatment Target in Dementia: a Roadmap for Designing Interventions.
Journal of Alzheimer's Disease,
88(4), 1203-1228.
Abstract:
Psychosis as a Treatment Target in Dementia: a Roadmap for Designing Interventions
Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.
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Ismail Z, Creese B, Aarsland D, Kales HC, Lyketsos CG, Sweet RA, Ballard C (2022). Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities.
Nature reviews. Neurology,
18(3), 131-144.
Abstract:
Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities.
Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.
Abstract.
Creese B, Aarsland D, Ballard CG, Brooker H, Corbett A, Ismail Z (2022). The association of the of late‐life onset psychotic symptoms with incident cognitive impairment in a cognitively normal sample. Alzheimer's & Dementia, 18(S7).
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).
Da Silva MV, Melendez‐Torres GJ, Testad I, Ballard C, Creese B (2021). A data‐driven examination of clustering of apathy and depression symptoms in people with dementia. Alzheimer's & Dementia, 17(S6).
Imm JL, Harvey J, Pishva E, Creese B, Chouliaras L, Dempster E, Ballard C, O'Brien JT, Aarsland D, Mill J, et al (2021). A role for epigenetic mechanisms in Lewy body dementias.
Alzheimers Dement,
17 Suppl 3Abstract:
A role for epigenetic mechanisms in Lewy body dementias.
BACKGROUND: the Lewy body diseases, Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and Parkinson's disease dementia (PDD) are all neurodegenerative diseases classified by the accumulation of alpha-synuclein in neurons, forming Lewy bodies (LB). We hypothesise that these LBs cause epigenetic changes within neurons and surrounding cells and that these changes can be used to distinguish the different LB diseases from one another. METHOD: Bulk tissue from the cingulate gyrus and prefrontal cortex will be as analysed for DNA methylation levels using the Illumina Infinium Methylation EPIC array to generate quantitative methylation data for over 850,000 CpG sites across the genome (n=∼100/disease group). Linear regression and pathway analyses will be used to identify loci that are significantly different or specific to each disease. Following this we will validate loci and determine their cellular specificity using a subset of samples (15 DLB, 15 PDD, 15 PD only, 15 controls) using fluorescence activated cell sorting (FACS). In each sample we will isolate various different cellular populations, including neurons, microglia, oligodendrocytes and astrocytes before profiling these using the EPIC array. RESULT: Study groups have been sourced consisting of cases with PD, PDD and DLB based on LB deposition and clinical symptom staging. Control cases have been selected for matched age and levels of concomitant AD pathology. Cases for FACS (n=15/group) have been selected to allow where possible a high base RIN, pH and minimal post-mortem interval. CONCLUSION: We are collating a well powered study cohort to interrogate the epigenetic basis of neuropathological progression and clinical staging of LB disease, controlling for levels of concomitant AD pathology. Follow up FACS sorting and analysis will allow for the cell specific methylation changes occurring in each of the LB diseases.
Abstract.
Author URL.
Sun N, Ismail Z, Aarsland D, Brooker H, Corbett A, Ballard C, Creese B (2021). Examination of cognitive performance and mild behavioral impairment domains of apathy, mood, impulse dyscontrol, social inappropriateness and psychosis in cognitively normal adults aged 50 and over. Alzheimer's & Dementia, 17(S6).
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I, Moreno-Grau S, Tárraga L, et al (2021). Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular Psychiatry, 26(10), 5797-5811.
Brooker H, Hayman V, Aarsland D, Creese B, Ballard C, Corbett A (2021). Impact of brisk walking on cognitive decline in adults with and without early impairment: a FLAME analysis in the PROTECT cohort. Alzheimer's & Dementia, 17(S10).
Creese B, Arathimos R, Brooker H, Corbett A, Aarsland D, Lewis C, Ballard C, Ismail Z (2021). Self and informant‐rated mild behavioral impairment and genetic risk for AD: the respondent matters. Alzheimer's & Dementia, 17(S6).
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.
Brooker H, Hayman V, Aarsland D, Creese B, Ballard C, Corbett A (2021). The impact of the COVID‐19 pandemic on cognitive health. Alzheimer's & Dementia, 17(Suppl 10).
Surr CA, Holloway I, Walwyn RE, Griffiths AW, Meads D, Kelley R, Martin A, McLellan V, Ballard C, Fossey J, et al (2020). Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT.
Health Technol Assess,
24(16), 1-172.
Abstract:
Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT.
BACKGROUND: the quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. OBJECTIVE: to investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. DESIGN: a pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. SETTING: Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. PARTICIPANTS: Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer's Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. INTERVENTION: Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. MAIN OUTCOME MEASURES: the primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. RESULTS: There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was -2.11 points, being lower in the intervention group than in the control (95% confidence interval -4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. LIMITATIONS: the primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. CONCLUSIONS: There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. FUTURE WORK: Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information.
Abstract.
Author URL.
Creese B, Albertyn CP, Dworkin S, Thomas RS, Wan YM, Ballard C (2020). Executive function but not episodic memory decline associated with visual hallucinations in Parkinson's disease.
J Neuropsychol,
14(1), 85-97.
Abstract:
Executive function but not episodic memory decline associated with visual hallucinations in Parkinson's disease.
INTRODUCTION: Visual hallucinations (VH) have a significant impact on quality of life for people with Parkinson's disease (PD). A major reason for this is the well-established link with cognitive impairment, but there is still a need for more longitudinal studies examining the specific cognitive domains which may be affected. The aim of this study was to profile decline in cognition associated with VH in a cohort of 69 individuals with PD over 1 year. METHOD: Visual hallucinations assessments were carried out every 3 months. Executive function and episodic memory were assessed at baseline and 1 year. All evaluations were performed via phone interviews. The presence or absence of VH was categorized based on the entirety of the year's data (i.e. no episodes and >0 episodes). We also defined a persistent VH group who had VH present at more than one time point and compared these with a no-VH group and a group with transient VH (i.e. only one episode). RESULTS: Linear mixed-effect models showed that VH were associated with more rapid overall cognitive decline (-0.26, t = -2.39, p = .02), which was driven by executive function (-0.28, t = -2.48, p = .02). Persistent VH were associated with decline in executive function (-0.33, t = -2.4, p = .02), while no relationship was found for non-persistent VH, suggesting that persistent VH be the major driver of this relationship. CONCLUSION: This finding brings greater clarity to the relationship between cognitive decline and VH in PD. Future research should examine the robustness of this phenotype for biomarkers studies and treatment interventions.
Abstract.
Author URL.
Creese B, Malekizadeh Y, Williams G, Whitfield D, Kelson M, Ballard C, Mill J, Jeffries A (2020). In‐silico high throughput whole transcriptome screening implicates cardiovascular disease and the immune system in the mechanism of action underlying adverse effects of atypical antipsychotics. Alzheimer's & Dementia, 16(S9).
Ballard C, Kales HC, Lyketsos C, Aarsland D, Creese B, Mills R, Williams H, Sweet RA (2020). Psychosis in Alzheimer's Disease.
Curr Neurol Neurosci Rep,
20(12).
Abstract:
Psychosis in Alzheimer's Disease.
PURPOSE OF REVIEW: to review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). RECENT FINDINGS: Psychosis in Alzheimer's disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets.
Abstract.
Author URL.
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.
Creese B, Ballard C, Vasconcelos Da Silva M (2019). Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer’s disease. Translational Psychiatry
Da Silva MV, Creese B, Johar I, Bergh S, Aarsland D, Rongve A, Medboen IT, Aakhus E, Andersen F, Braekhus A, et al (2019). O2‐11‐06: THE COURSE OF APATHY IN PEOPLE WITH DEMENTIA. Alzheimer's & Dementia, 15(7S_Part_11), p570-p570.
Da Silva MV, Creese B, Johar I, Aarsland D, Bergh S, Athanasiu L, Rongve A, Medboen IT, Aakhus E, Andersen F, et al (2019). P1‐131: GENOME WIDE ASSOCIATION STUDY: IDENTIFYING GENETIC MARKERS IN APATHY IN PEOPLE WITH ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 15(7S_Part_5), p286-p286.
Creese B, Brooker H, Wesnes K, Corbett A, Aarsland D, Ismail Z, Ballard C (2019). P1‐468: CHARACTERISING THE COGNITIVE PROFILE ASSOCIATED WITH INDIVIDUAL DOMAINS OF MID BEHAVIOURAL IMPAIRMENT IN THE COGNITIVELY NORMAL POPULATION. Alzheimer's & Dementia, 15(7S_Part_8), p447-p448.
Ballard C, Creese B, Chambers D, Williams G (2019). P2‐110: a NEURONAL CONNECTIVITY MAP (NMAP) DATABASE TO ESTABLISH a DRUG‐SCREENING PLATFORM FOR AD. Alzheimer's & Dementia, 15(7S_Part_12), p614-p614.
Johar I, Creese B, Bergh S, Athanasiu L, Medboen IT, Da Silva MV, Rongve A, Aakhus E, Anderson F, Bettella F, et al (2019). P2‐129: GENOME‐WIDE ASSOCIATION OF ALZHEIMER'S DISEASE WITH DYSPHORIA AND EVALUATION OF GENETIC OVERLAP WITH MAJOR DEPRESSIVE DISORDER. Alzheimer's & Dementia, 15(7S_Part_12), p621-p622.
Gatt A, Whitfield D, Creese B, Ballard C (2019). P3‐228: a MULTIPLEX BIOMARKER ASSAY FOR MEASURING TRANSCRIPTIONAL CHANGES IN THE 5XFAD MOUSE MODEL OF AD. Alzheimer's & Dementia, 15(7S_Part_19), p1019-p1019.
Creese B, Brooker H, Corbett A, Aarsland D, Ballard C (2019). P3‐319: FAMILY HISTORY OF DEMENTIA WITH PSYCHOTIC SYMPTOMS IN THE COGNITIVELY NORMAL POPULATION: FEASIBILITY OF MEASUREMENT AND INITIAL CLINICAL AND GENETIC ASSOCIATIONS. Alzheimer's & Dementia, 15(7S_Part_20), p1059-p1059.
Creese B, Brooker H, Corbett A, Ismail Z, Aarsland D, Ballard C (2019). P4‐248: EVALUATING SHARED GENETIC LIABILITY FOR LATE‐LIFE ABNORMAL THOUGHTS AND PERCEPTION (MILD BEHAVIORAL IMPAIRMENT), AND NEUROLOGICAL AND PSYCHIATRIC CONDITIONS. Alzheimer's & Dementia, 15(7S_Part_26), p1374-p1374.
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
Griffiths AW, Surr CA, Creese B, Garrod L, Chenoweth L (2019). The development and use of the assessment of dementia awareness and person-centred care training tool in long-term care.
Dementia (London),
18(7-8), 3059-3070.
Author URL.
Griffiths AW, Albertyn CP, Burnley NL, Creese B, Walwyn R, Holloway I, Safarikova J, Surr CA (2019). Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) tool - ERRATUM.
International Psychogeriatrics,
32(2), 287-287.
Abstract:
Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) tool - ERRATUM
The above article (Griffiths et al. 2019) published with an incorrect abstract.The correct abstract is as follows:Objectives:Behaviours associated with agitation are common in people living with dementia. The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale widely used to assess agitation completed by a proxy (family carer or staff member). However, proxy informants introduce possible reporting bias when blinding to the treatment arm is not possible, and potential accuracy issues due to irregular contact between the proxy and the person with dementia over the reporting period. An observational measure completed by a blinded researcher may address these issues, but no agitation measures with comparable items exist.Design:Development and validation of an observational version of the CMAI (CMAI-O), to assess its validity as an alternative or complementary measure of agitation.Setting:Fifty care homes in England.Participants:Residents (N = 726) with dementia.Measurements:Two observational measures (CMAI-O and PAS) were completed by an independent researcher. Measures of agitation, functional status, and neuropsychiatric symptoms were completed with staff proxies.Results:The CMAI-O showed adequate internal consistency (α =. 61), criterion validity with the PAS (r =. 79, p = <. 001), incremental validity in predicting quality of life beyond the Functional Assessment Staging of Alzheimer’s disease (β = 1.83, p <. 001 at baseline) and discriminant validity from the Neuropsychiatric Inventory Apathy subscale (r =. 004, p =. 902).Conclusions:The CMAI-O is a promising research tool for independently measuring agitation in people with dementia in care homes. Its use alongside the CMAI could provide a more robust understanding of agitation amongst residents with dementia.
Abstract.
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.
Creese B, Bell E, Johar I, Francis P, Ballard C, Aarsland D (2018). Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson's disease and Lewy body dementias: Review and meta-analyses.
Am J Med Genet B Neuropsychiatr Genet,
177(2), 232-241.
Abstract:
Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson's disease and Lewy body dementias: Review and meta-analyses.
Heterozygous mutations in glucocerebrosidase gene (GBA) are a major genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, there has been a considerable focus on the relationship between GBA mutations and emergence of cognitive impairment and neuropsychiatric symptoms in these diseases. Here, we review the literature in this area, with a particular focus, including meta-analysis, on the key neuropsychiatric symptoms of cognitive impairment, psychosis, and depression in Parkinson's disease. Our meta-analysis demonstrated that GBA mutations are associated with a 2.4-fold increased risk of cognitive impairment. In addition, our novel meta-analyses of psychosis and depression showed a 1.8- and 2.2-fold increased risk respectively associated with GBA mutations, although due to possible bias and heterogeneity the depression findings should be interpreted with caution. While the precise mechanisms which increase susceptibility to neurodegeneration in GBA carriers are not known, evidence of greater cortical Lewy body pathology, reduced patterns of cortical activation, and hippocampal pathology in animal models are all consistent with a direct effect of GBA mutations on these symptoms. Extension of this work in DLB and individuals without neurodegeneration will be important in further characterizing how GBA mutations increase risk for PD and DLB and influence disease course.
Abstract.
Author URL.
Surr C, Holloway I, Walwyn RE, Griffiths AW, Meads D, Kelley R, Martin A, McLellan V, Ballard C, Fossey J, et al (2018). O3‐08‐06: RESULTS OF a PRAGMATIC, CLUSTER RANDOMISED, CONTROLLED TRIAL OF THE EFFECTIVENESS AND COST‐EFFECTIVENESS OF DEMENTIA CARE MAPPING (DCM) IN UK CARE HOMES (DCM EPIC TRIAL). Alzheimer's & Dementia, 14(7S_Part_19), p1035-p1035.
Creese B, Bergh S, Aarsland D, Andersen F, Brooker H, Corbett A, Khan Z, Megalogeni M, Rongve A, Stordal E, et al (2018). P1‐151: GENETIC OVERLAP BETWEEN PSYCHOTIC SYMPTOMS ACROSS THE LIFESPAN: FINDINGS FROM SCHIZOPHRENIA, COGNITIVELY NORMAL OLDER ADULTS AND ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 14(7S_Part_6).
Brooker H, Creese B, Ismail Z, Khan Z, Megalogeni M, Corbett A, Hampshire A, Aarsland D, Ballard C, Wesnes K, et al (2018). P1‐523: THE RELATIONSHIP BETWEEN THE MILD BEHAVIOURAL IMPAIRMENT CHECKLIST (MBI‐C) TOTAL SCORE AND CORE ASPECTS OF COGNITIVE FUNCTION IN OLDER ADULTS. Alzheimer's & Dementia, 14(7S_Part_9).
Creese B, Pishva E, Proitsi P, Smith RG, Ballard C, Hove DLA, Mill J, Lunnon K (2018). P2‐143: PSYCHOSIS‐ASSOCIATED EPIGENETIC VARIATION IN PATIENTS WITH ALZHEIMER'S DISEASE ACROSS CORTICAL BRAIN REGIONS. Alzheimer's & Dementia, 14(7S_Part_13), p723-p723.
Wesnes K, Brooker H, Creese B, Khan Z, Megalogeni M, Corbett A, Davis K, Hotopf M, Aarsland D, Ballard C, et al (2018). P2‐483: DEPRESSION IS ASSOCIATED WITH IMPAIRMENT IN COGNITIVE FUNCTION IN ADULTS AGED 50 AND OVER. Alzheimer's & Dementia, 14(7S_Part_16).
Creese B, Brooker H, Ismail Z, Aarsland D, Corbett A, Khan Z, Megalogeni M, Ballard C, Wesnes K (2018). P3‐554: PROFILE OF MILD BEHAVIOURAL IMPAIRMENT IN a POPULATION‐BASED SAMPLE OF ADULTS AGED 50 AND OVER: INITIAL FINDINGS FROM THE PROTECT STUDY. Alzheimer's & Dementia, 14(7S_Part_25).
Creese B, Da Silva MV, Johar I, Ballard C (2018). The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.
Expert Rev Neurother,
18(6), 461-467.
Abstract:
The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.
Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions. Expert commentary: the current justification for antipsychotic use in the context of the changing landscape of prescribing and provide a view on the most promising alternative candidates to this class of drug are appraised.
Abstract.
Author URL.
Aarsland D, Creese B, Chaudhuri KR (2017). A new tool to identify patients with Parkinson's disease at increased risk of dementia.
Lancet Neurol,
16(8), 576-578.
Author URL.
Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, Ballard C (2017). Cognitive decline in Parkinson disease.
Nat Rev Neurol,
13(4), 217-231.
Abstract:
Cognitive decline in Parkinson disease.
Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.
Abstract.
Author URL.
Ffytche DH, Creese B, Politis M, Chaudhuri KR, Weintraub D, Ballard C, Aarsland D (2017). The psychosis spectrum in Parkinson disease.
Nat Rev Neurol,
13(2), 81-95.
Abstract:
The psychosis spectrum in Parkinson disease.
In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors - for example, autonomic dysfunction - that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.
Abstract.
Author URL.
Creese B, Ballard C, Aarsland D, Bergh S, Rongve A, Selbaek G (2017). [P1–299]: AN EVALUATION OF PREDICTORS AND COGNITIVE DECLINE ASSOCIATED WITH PERSISTENT AND TRANSIENT PSYCHOTIC SYMPTOMS IN ALZHEIMER's DISEASE. Alzheimer's & Dementia, 13(7S_Part_7), p367-p367.
Johar I, Aarsland D, Ballard C, Bergh S, Fossey J, Kirkevold Ø, Medboen IT, Orrell M, Rongve A, Selbaek G, et al (2017). [P1–309]: PREVALENCE AND CO‐MORBIDITY OF APATHY AND DEPRESSION IN ALZHEIMER's DISEASE. Alzheimer's & Dementia, 13(7S_Part_7), p371-p372.
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, 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.
Surr C, Lilley-Kelly A, Graham L, Walwyn R, Cicero R, Griffiths A, Creese B, Garrod L (2015). Complexities of trial recruitment in the care home setting: an illustration via the DCM™epic (dementia care mapping™: to enable person-centred care in care homes) trial. Trials, 16(Suppl 2).
Creese B, Ballard C, Aarsland D, Londos E, Sharp S, Jones E (2014). Determining the Association of the 5HTTLPR Polymorphism with Delusions and Hallucinations in Lewy Body Dementias. The American Journal of Geriatric Psychiatry, 22(6), 580-586.
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.
Creese B, Ballard C, Jones E (2013). Cognitive Impairment in Studies of 5HTTLPR and Psychosis in Alzheimer’s Disease: a Systematic Review.
Dementia and Geriatric Cognitive Disorders,
35(3-4), 155-164.
Abstract:
Cognitive Impairment in Studies of 5HTTLPR and Psychosis in Alzheimer’s Disease: a Systematic Review
<b><i>Background/Aims:</i></b> Cognitive impairment is a well-established correlate of psychotic symptoms in Alzheimer’s disease (AD-P). We review whether this relationship has confounded previous genetic association studies of 5HTTLPR and AD-P. <b><i>Methods:</i></b> We reviewed all studies on 5HTTLPR and conducted a semi-quantitative analysis. <b><i>Results:</i></b> Three out of 4 studies with low MMSE reported a significant association, while 1 out of 4 with high MMSE reported a significant association. <b><i>Conclusions:</i></b> Variation in cognitive impairment in past studies has contributed to the inconsistency in findings. The findings presented here bring a greater clarity to our understanding of the role of 5HTTLPR in AD-P.
Abstract.
Creese B, Ballard C, Aarsland D, Londos E, Sharp S, Jones E (2012). No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias. Neuroscience Letters, 531(1), 1-4.
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.
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.
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.
Conferences
Arathimos R, Fabbri C, Vassos E, Davis K, Pain O, Gillett A, Coleman J, Hanscombe KB, Hagenaars S, Jermy B, et al (2021). LATENT SUBTYPES OF MANIC OR IRRITABLE EPISODE SYMPTOMS IN TWO POPULATION-BASED COHORTS.
Author URL.
Publications by year
In Press
Creese B (In Press). A Data-Driven Examination of Apathy and Depressive Symptoms in Dementia with Independent Replication. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Smith S, Griffiths AW, Creese B, Sass C, Surr C (In Press). A biopsychosocial interpretation of the Neuropsychiatric Inventory-Nursing Home (NH): reconceptualising psychiatric symptom attributions. BJPsych Open
Creese B (In Press). A longitudinal study of late-life psychosis and incident dementia and the potential effects of race and cognition. Nature Mental Health
Creese B, Vassos E, Bergh S, Athanasiu L, Johar I, Rongve A, Medbøen IT, Da Silva MV, Aakhus E, Andersen F, et al (In Press). Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer’s disease: meta-analysis of 11 cohort studies.
Abstract:
Association between schizophrenia polygenic score and psychotic symptoms in Alzheimer’s disease: meta-analysis of 11 cohort studies
AbstractBackgroundPsychosis (delusions and hallucinations) is common in Alzheimer’s disease (AD) and associated with worse clinical outcomes including accelerated cognitive decline and shorter time to nursing home admission. Atypical antipsychotics have limited efficacy which, along with emerging genomic research, suggests some overlapping mechanisms with other disorders characterized by psychosis, like schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with psychotic symptoms in AD.MethodsSchizophrenia PRS was calculated using Psychiatric Genomics Consortium data at 10 GWAS p-value thresholds (PT) in 3,173 AD cases from 11 cohort studies. Association between PRS and AD psychosis status was tested by logistic regression in each cohort individually and the results meta-analyzed.ResultsThe schizophrenia PRS was associated with psychosis in AD at an optimumPTof the strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.17-fold increased risk (95% CI: 1.07-1.3; p=0.001).ConclusionThese new findings point towards psychosis in AD – and particularly delusions – sharing some genetic liability with schizophrenia, and support a transdiagnostic view of psychotic symptoms across the lifespan.
Abstract.
Creese B, Ballard C (In Press). Cost-effectiveness of Dementia Care Mapping in care home settings – Evaluation of a randomised controlled trial. Applied Health Economics and Health Policy
Surr C, Holloway I, Walwyn REA, Grifiths AW, Meads D, Martin A, Kelley R, Ballard C, Fossey J, Burnley N, et al (In Press). Effectiveness of Dementia Care Mapping™ to reduce agitation in care home residents with dementia: an open-cohort cluster randomised controlled trial. Aging and Mental Health
Lunnon K, Harvey J, Smith A, Weymouth L, Smith R, Castanho I, Hubbard L, Creese B, Bresner K, Williams N, et al (In Press). Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: a DNA co-methylation network analysis.
Abstract:
Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: a DNA co-methylation network analysis
Abstract
. Parkinson’s disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinson’s disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms and with ontological enrichment for terms relevant to neuronal and synaptic processes. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regard to depressive symptoms in Parkinson’s disease.
Abstract.
Harvey J, Smith AR, Weymouth LS, Smith RG, Castanho I, Hubbard L, Creese B, Bresner K, Williams N, Pishva E, et al (In Press). Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: a DNA co-methylation network analysis.
Abstract:
Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: a DNA co-methylation network analysis
AbstractParkinson’s disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinson’s disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms and with ontological enrichment for terms relevant to neuronal and synaptic processes. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regard to depressive symptoms in Parkinson’s disease.
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
Wolfova K, Creese B, Aarsland D, Ismail Z, Corbett A, Ballard C, Hampshire A, Cermakova P (In Press). Gender/sex differences in the association of mild behavioral impairment with cognitive aging. Journal of Alzheimer's Disease
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
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I, Moreno-Grau S, Tárraga L, et al (In Press). Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease.
Abstract:
Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease
AbstractPsychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD+P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.
Abstract.
Wang J, Spencer A, Hulme C, Corbett A, Khan Z, Vasconcelos Da Silva M, O'Dwyer S, Wright N, Testad I, Ballard C, et al (In Press). Healthcare utilisation and physical activities for older adults with comorbidities in the UK during COVID-19. Health and Social Care in the Community
Wang J, Spencer A, Hulme C, Khan Z, Vasconcelos Da Silva M, O'Dwyer S, Wright N, Testad I, Ballard C, Creese B, et al (In Press). Healthcare utilisation, physical activity and mental health during COVID-19 lockdown: an interrupted time-series analysis of older adults in England. European Journal of Ageing
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.
Creese B, Arathimos R, Aarsland D, Ballard C, Brooker H, Hampshire A, Corbett A, Ismail Z (In Press). Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: modification by genetic risk for Alzheimer’s disease. Alzheimer's and Dementia: Translational Research and Clinical Interventions
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 and/or irritable episode symptoms in two 1 population-based cohorts. British Journal of Psychiatry
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.
Lennon M, Brooker H, Creese B, Thayanandan T, Rigney G, Aarsland D, Hampshire A, Ballard C, Corbett A, Raymont V, et al (In Press). Lifetime TBI and cognitive domain deficits in late life: the PROTECT-TBI cohort study. Journal of Neurotrauma
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
Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen L, Rutten BPF, Shireby G, Torkamani A, Creese B, et al (In Press). Machine learning-based prediction of cognitive outcomes in de novo Parkinson’s disease.
Abstract:
Machine learning-based prediction of cognitive outcomes in de novo Parkinson’s disease
AbstractCognitive impairment is a debilitating symptom in Parkinson’s disease (PD). We aimed to establish an accurate multivariate machine learning (ML) model to predict cognitive outcome in newly diagnosed PD cases from the Parkinson’s Progression Markers Initiative (PPMI). Annual cognitive assessments over an eight-year time span were used to define two cognitive outcomes of i) cognitive impairment, and ii) dementia conversion. Selected baseline variables were organized into three subsets of clinical, biofluid and genetic/epigenetic measures and tested using four different ML algorithms. Irrespective of the ML algorithm used, the models consisting of the clinical variables performed best and showed better prediction of cognitive impairment outcome over dementia conversion. We observed a marginal improvement in the prediction performance when clinical, biofluid, and epigenetic/genetic variables were all included in one model. Several cerebrospinal fluid measures and an epigenetic marker showed high predictive weighting in multiple models when included alongside clinical variables.
Abstract.
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
Creese B, Ismail Z (In Press). Mild Behavioral Impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease.
Alzheimer's Research and TherapyAbstract:
Mild Behavioral Impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease
Background: Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was established to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease.
Main: MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10-15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people.
Conclusion: the emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease.
Abstract.
Daunt P, Ballard C, Creese B, Davidson G, Hardy J, Oshota O, Pither RJ, Gibson AM (In Press). Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease. The journal of prevention of Alzheimer's disease
Pishva SE, Creese B, Smith A, Ballard C, Mill J, Lunnon K (In Press). Psychosis-associated DNA methylomic variation in Alzheimer’s disease cortex. Neurobiology of Aging
Creese B, Ballard C (In Press). Revisiting criteria for psychosis in Alzheimer’s disease and related dementias- towards better phenotypic classification and biomarker research. Journal of Alzheimer's Disease
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.
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
Griffiths A, Albertyn C, Burnley N, Creese BA, Walwyn R, Holloway I, Safarikova J, Surr C (In Press). Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) Tool. International Psychogeriatrics
Malekizadeh Y, Williams G, Kelson M, Whitfield D, Mill J, Collier D, Ballard C, Jeffries A, Creese B (In Press). Whole transcriptome in-silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects. Alzheimer's and Dementia: Translational Research and Clinical Interventions
2023
Rogowska M, Thornton M, Creese B, Velayudhan L, Aarsland D, Ballard C, Tsamakis K, Stewart R, Mueller C (2023). Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: a 2011-2022 Update.
Drugs Aging,
40(1), 21-32.
Abstract:
Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: a 2011-2022 Update.
Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.
Abstract.
Author URL.
Gilchrist L, Spargo TP, Green RE, Coleman JRI, Howard DM, Thorp JG, Adey B, Lord J, Davies HL, Mundy J, et al (2023). Investigating the genetic relationship between depression symptoms and Alzheimer’s Disease in clinically diagnosed and proxy cases.
Munir A, Ghahremani M, Smith EE, Creese B, Fischer CE, Ismail Z (2023). Late life onset of persistent psychosis and incident dementia: risk stratification by baseline cognitive status. Alzheimer's & Dementia, 19(S4).
Packer A, Corbett A, Arathimos R, Ballard C, Aarsland D, Hampshire A, Dima D, Creese B, Malanchini M, Powell TR, et al (2023). Limited evidence of a shared genetic relationship between C-reactive protein levels and cognitive function in older UK adults of European ancestry. Frontiers in Dementia, 2
Ghahremani M, Chen H, Creese B, Goodarzi Z, Smith EE, Ismail Z (2023). Longitudinal association between exposure to vitamin D supplementation and incident dementia – a study of dementia‐free older adults. Alzheimer's & Dementia, 19(S8).
Ismail Z, Leon R, Creese B, Ballard C, Robert P, Smith EE (2023). Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO.
Molecular Neurodegeneration,
18(1).
Abstract:
Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO
Abstract
. Background
. Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally.
.
. Methods
. Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions).
.
. Results
. of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p < 0.001), and t-tau/Aβ42 (p = 0.001). NPSnotMBI was associated only with lower Aβ42/40 (p = 0.045). LMEs revealed a similar 4-year AD-specific biomarker profile for MBI, with NPSnotMBI associated only with higher t-tau. MBI had a greater rate of incident dementia (HR [95%CI], 3.50 [1.99–6.17; p < 0.001). NPSnotMBI did not differ from noNPS (HR 0.96 [0.49–1.89]; p = 0.916). In MEMENTO, MBI demonstrated a similar magnitude and direction of effect for all biomarkers, but with a greater reduction in Aβ40. HR for incident dementia was 3.93 (p = 0.004) in MBI, and 1.83 (p = 0.266) in NPSnotMBI. of MBI progressors to dementia, 81% developed AD dementia.
.
. Conclusions
. These findings support a biological basis for NPS that meet MBI criteria, the continued inclusion of MBI in NIA-AA ATN clinical staging, and the utility of MBI criteria to improve identification of patients for enrollment in disease-modifying drug trials or for clinical care.
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Abstract.
Albertyn CP, Johar I, Creese B, Young A, Carter B, Velayudhan L, Bhattacharyya S, Vasconcelos Da Silva M, Samsi K, Jafari H, et al (2023). Sativex® for the treatment of Agitation & Aggression in Alzheimer’s Dementia in UK nursing homes (STAND): Protocol for a feasibility randomised controlled trial. Health Open Research, 5
Stewart GR, Corbett A, Ballard C, Creese B, Aarsland D, Hampshire A, Charlton RA, Happé F (2023). Self-harm and Suicidality Experiences of Middle-Age and Older Adults with vs. Without High Autistic Traits.
J Autism Dev Disord,
53(8), 3034-3046.
Abstract:
Self-harm and Suicidality Experiences of Middle-Age and Older Adults with vs. Without High Autistic Traits.
Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours.
Abstract.
Author URL.
Kouhsar MP, Creese B, Weymouth LS, Smith AR, Bergh S, Wedatilake Y, Selbæk G, Torkamani A, Mill J, Ballard CG, et al (2023). Transcription‐based drug repurposing in Alzheimer disease psychosis. Alzheimer's & Dementia, 19(S1).
Ghahremani M, Smith EE, Chen H-Y, Creese B, Goodarzi Z, Ismail Z (2023). Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status.
Alzheimers Dement (Amst),
15(1).
Abstract:
Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status.
INTRODUCTION: Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia-free persons from the National Alzheimer's Coordinating Center. METHODS: Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D-. Kaplan-Meier curves compared dementia-free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E (APOE) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. RESULTS: Across all formulations, vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55-0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. DISCUSSION: Vitamin D may be a potential agent for dementia prevention. HIGHLIGHTS: in a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset.Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure.Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment.Vitamin D effects were significantly greater in apolipoprotein E ε4 non-carriers versus carriers.Vitamin D has potential for dementia prevention, especially in the high-risk strata.
Abstract.
Author URL.
2022
Da Silva MV, Melendez-Torres GJ, Ismail Z, Testad I, Ballard C, Creese B, Initiative TADN (2022). A DATA-DRIVEN EXAMINATION OF APATHY AND DEPRESSIVE SYMPTOMS IN DEMENTIA WITH INDEPENDENT REPLICATION.
Imm JL, Harvey J, Creese B, Chouliaras L, Dempster E, Ballard CG, O'Brien JT, Aarsland D, Mill J, Pishva E, et al (2022). A Role for Epigenetic Mechanisms in the Lewy Body Dementias. Alzheimer's & Dementia, 18(S3).
Weymouth LS, Kouhsar MP, Creese B, Bergh S, Wedatilake Y, Torkamani A, Smith AR, Selbaek G, Sweet R, Ballard CG, et al (2022). An Epigenome‐wide association study of psychosis in Alzheimer's disease dorsolateral prefrontal cortex. Alzheimer's & Dementia, 18(S4).
Harvey J, Smith AR, Weymouth LS, Smith RG, Hubbard L, Bresner K, Pishva E, Williams N, Lunnon K, Creese B, et al (2022). An epigenome wide association study of sub‐phenotypes in Parkinson’s disease. Alzheimer's & Dementia, 18(S4).
Singham T, Saunders R, Brooker H, Creese B, Aarsland D, Hampshire A, Ballard C, Corbett A, Desai R, Stott J, et al (2022). Are subtypes of affective symptoms differentially associated with change in cognition over time: a latent class analysis.
J Affect Disord,
309, 437-445.
Abstract:
Are subtypes of affective symptoms differentially associated with change in cognition over time: a latent class analysis.
BACKGROUND: in the absence of disease-modifying treatments, identifying potential psychosocial risk factors for dementia is paramount. Depression and anxiety have been identified as potential risk factors. Studies however have yielded mixed findings, lending possibility to the fact that potential constellations of co-occurring depression and anxiety symptoms may better explain the link between affective symptoms and cognitive decline. METHODS: Data from participants (aged 50 and above) of the PROTECT study was used. Latent Class Analysis (LCA) was conducted on 21,684 participants with baseline anxiety and depression measures. Multiple linear regressions models, using a subset of these participants (N = 6136) who had complete cognition data at baseline and at 2-year follow-up, were conducted to assess for associations between class membership and longitudinal changes in cognition. RESULTS: the LCA identified a 5-class solution: "No Symptoms", "Sleep", "Sleep and Worry", "Sleep and Anhedonia", and "Co-morbid Depression and Anxiety". Class membership was significantly associated with longitudinal change in cognition. Furthermore, this association differed across different cognitive measures. LIMITATIONS: Limitations included significant attrition and a generally healthy sample which may impact generalisability. CONCLUSIONS: Substantial heterogeneity in affective symptoms could explain previous inconsistent findings concerning the association between affective symptoms and cognition. Clinicians should not focus solely on total symptom scores on a single affective domain, but instead on the presence and patterns of symptoms (even if sub-clinical) on measures across multiple affective domains. Identifying particular subgroups that are at greater risk of poor cognitive outcomes may support targeted prevention work.
Abstract.
Author URL.
Gibbons E, Rongve A, de Rojas I, Shadrin A, Westra K, Baumgartner A, Rosendall L, Madaj Z, Hernandez DG, Ross OA, et al (2022). Identification of a sex-specific genetic signature in dementia with Lewy bodies: a meta-analysis of genome-wide association studies.
Creese B, Arathimos R, Aarsland D, Ballard C, Corbett A, Ismail Z (2022). Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: modification by genetic risk for Alzheimer’s disease.
Arathimos R, Fabbri C, Vassos E, Davis KAS, Pain O, Gillett A, Coleman JRI, Hanscombe K, Hagenaars S, Jermy B, et al (2022). Latent subtypes of manic and/or irritable episode symptoms in two population-based cohorts - ERRATUM.
Br J Psychiatry, 1-2.
Author URL.
Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen L, Rutten BP, Shireby G, Torkamani A, Creese B, et al (2022). Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.
Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen L, Rutten BPF, Shireby G, Torkamani A, Creese B, et al (2022). Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.
NPJ Parkinsons Dis,
8(1).
Abstract:
Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.
Cognitive impairment is a debilitating symptom in Parkinson's disease (PD). We aimed to establish an accurate multivariate machine learning (ML) model to predict cognitive outcome in newly diagnosed PD cases from the Parkinson's Progression Markers Initiative (PPMI). Annual cognitive assessments over an 8-year time span were used to define two cognitive outcomes of (i) cognitive impairment, and (ii) dementia conversion. Selected baseline variables were organized into three subsets of clinical, biofluid and genetic/epigenetic measures and tested using four different ML algorithms. Irrespective of the ML algorithm used, the models consisting of the clinical variables performed best and showed better prediction of cognitive impairment outcome over dementia conversion. We observed a marginal improvement in the prediction performance when clinical, biofluid, and epigenetic/genetic variables were all included in one model. Several cerebrospinal fluid measures and an epigenetic marker showed high predictive weighting in multiple models when included alongside clinical variables.
Abstract.
Author URL.
Harvey J, Reijnders RA, Cavill R, Duits A, Köhler S, Eijssen LMT, Rutten BPF, Shireby G, Torkamani A, Creese B, et al (2022). Machine learning‐based prediction of cognitive outcomes in de novo Parkinson's disease. Alzheimer's & Dementia, 18(S5).
Creese B, Lunnon K (2022). Neuropsychiatric symptoms in AD: the search for mechanisms. Nature Reviews Neurology, 18(11), 639-640.
Harvey J, Reijnders RA, Shireby G, Duits A, Köhler S, Creese B, Lunnon K, Pishva E (2022). Polygenic risk score association with cognitive decline in Parkinson’s Disease. Alzheimer's & Dementia, 18(S4).
Agüera-Ortiz L, Babulal GM, Bruneau M-A, Creese B, D’Antonio F, Fischer CE, Gatchel JR, Ismail Z, Kumar S, McGeown WJ, et al (2022). Psychosis as a Treatment Target in Dementia: a Roadmap for Designing Interventions.
Journal of Alzheimer's Disease,
88(4), 1203-1228.
Abstract:
Psychosis as a Treatment Target in Dementia: a Roadmap for Designing Interventions
Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.
Abstract.
Ismail Z, Creese B, Aarsland D, Kales HC, Lyketsos CG, Sweet RA, Ballard C (2022). Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities.
Nature reviews. Neurology,
18(3), 131-144.
Abstract:
Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities.
Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.
Abstract.
Creese B, Aarsland D, Ballard CG, Brooker H, Corbett A, Ismail Z (2022). The association of the of late‐life onset psychotic symptoms with incident cognitive impairment in a cognitively normal sample. Alzheimer's & Dementia, 18(S7).
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
Da Silva MV, Melendez‐Torres GJ, Testad I, Ballard C, Creese B (2021). A data‐driven examination of clustering of apathy and depression symptoms in people with dementia. Alzheimer's & Dementia, 17(S6).
Imm JL, Harvey J, Pishva E, Creese B, Chouliaras L, Dempster E, Ballard C, O'Brien JT, Aarsland D, Mill J, et al (2021). A role for epigenetic mechanisms in Lewy body dementias.
Alzheimers Dement,
17 Suppl 3Abstract:
A role for epigenetic mechanisms in Lewy body dementias.
BACKGROUND: the Lewy body diseases, Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and Parkinson's disease dementia (PDD) are all neurodegenerative diseases classified by the accumulation of alpha-synuclein in neurons, forming Lewy bodies (LB). We hypothesise that these LBs cause epigenetic changes within neurons and surrounding cells and that these changes can be used to distinguish the different LB diseases from one another. METHOD: Bulk tissue from the cingulate gyrus and prefrontal cortex will be as analysed for DNA methylation levels using the Illumina Infinium Methylation EPIC array to generate quantitative methylation data for over 850,000 CpG sites across the genome (n=∼100/disease group). Linear regression and pathway analyses will be used to identify loci that are significantly different or specific to each disease. Following this we will validate loci and determine their cellular specificity using a subset of samples (15 DLB, 15 PDD, 15 PD only, 15 controls) using fluorescence activated cell sorting (FACS). In each sample we will isolate various different cellular populations, including neurons, microglia, oligodendrocytes and astrocytes before profiling these using the EPIC array. RESULT: Study groups have been sourced consisting of cases with PD, PDD and DLB based on LB deposition and clinical symptom staging. Control cases have been selected for matched age and levels of concomitant AD pathology. Cases for FACS (n=15/group) have been selected to allow where possible a high base RIN, pH and minimal post-mortem interval. CONCLUSION: We are collating a well powered study cohort to interrogate the epigenetic basis of neuropathological progression and clinical staging of LB disease, controlling for levels of concomitant AD pathology. Follow up FACS sorting and analysis will allow for the cell specific methylation changes occurring in each of the LB diseases.
Abstract.
Author URL.
Sun N, Ismail Z, Aarsland D, Brooker H, Corbett A, Ballard C, Creese B (2021). Examination of cognitive performance and mild behavioral impairment domains of apathy, mood, impulse dyscontrol, social inappropriateness and psychosis in cognitively normal adults aged 50 and over. Alzheimer's & Dementia, 17(S6).
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I, Moreno-Grau S, Tárraga L, et al (2021). Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular Psychiatry, 26(10), 5797-5811.
Brooker H, Hayman V, Aarsland D, Creese B, Ballard C, Corbett A (2021). Impact of brisk walking on cognitive decline in adults with and without early impairment: a FLAME analysis in the PROTECT cohort. Alzheimer's & Dementia, 17(S10).
Arathimos R, Fabbri C, Vassos E, Davis K, Pain O, Gillett A, Coleman J, Hanscombe KB, Hagenaars S, Jermy B, et al (2021). LATENT SUBTYPES OF MANIC OR IRRITABLE EPISODE SYMPTOMS IN TWO POPULATION-BASED COHORTS.
Author URL.
Creese B, Arathimos R, Brooker H, Corbett A, Aarsland D, Lewis C, Ballard C, Ismail Z (2021). Self and informant‐rated mild behavioral impairment and genetic risk for AD: the respondent matters. Alzheimer's & Dementia, 17(S6).
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.
Abstract.
Author URL.
Brooker H, Hayman V, Aarsland D, Creese B, Ballard C, Corbett A (2021). The impact of the COVID‐19 pandemic on cognitive health. Alzheimer's & Dementia, 17(Suppl 10).
2020
Surr CA, Holloway I, Walwyn RE, Griffiths AW, Meads D, Kelley R, Martin A, McLellan V, Ballard C, Fossey J, et al (2020). Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT.
Health Technol Assess,
24(16), 1-172.
Abstract:
Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT.
BACKGROUND: the quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. OBJECTIVE: to investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. DESIGN: a pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. SETTING: Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. PARTICIPANTS: Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer's Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. INTERVENTION: Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. MAIN OUTCOME MEASURES: the primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. RESULTS: There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was -2.11 points, being lower in the intervention group than in the control (95% confidence interval -4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. LIMITATIONS: the primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. CONCLUSIONS: There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. FUTURE WORK: Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information.
Abstract.
Author URL.
Creese B, Albertyn CP, Dworkin S, Thomas RS, Wan YM, Ballard C (2020). Executive function but not episodic memory decline associated with visual hallucinations in Parkinson's disease.
J Neuropsychol,
14(1), 85-97.
Abstract:
Executive function but not episodic memory decline associated with visual hallucinations in Parkinson's disease.
INTRODUCTION: Visual hallucinations (VH) have a significant impact on quality of life for people with Parkinson's disease (PD). A major reason for this is the well-established link with cognitive impairment, but there is still a need for more longitudinal studies examining the specific cognitive domains which may be affected. The aim of this study was to profile decline in cognition associated with VH in a cohort of 69 individuals with PD over 1 year. METHOD: Visual hallucinations assessments were carried out every 3 months. Executive function and episodic memory were assessed at baseline and 1 year. All evaluations were performed via phone interviews. The presence or absence of VH was categorized based on the entirety of the year's data (i.e. no episodes and >0 episodes). We also defined a persistent VH group who had VH present at more than one time point and compared these with a no-VH group and a group with transient VH (i.e. only one episode). RESULTS: Linear mixed-effect models showed that VH were associated with more rapid overall cognitive decline (-0.26, t = -2.39, p = .02), which was driven by executive function (-0.28, t = -2.48, p = .02). Persistent VH were associated with decline in executive function (-0.33, t = -2.4, p = .02), while no relationship was found for non-persistent VH, suggesting that persistent VH be the major driver of this relationship. CONCLUSION: This finding brings greater clarity to the relationship between cognitive decline and VH in PD. Future research should examine the robustness of this phenotype for biomarkers studies and treatment interventions.
Abstract.
Author URL.
Creese B, Malekizadeh Y, Williams G, Whitfield D, Kelson M, Ballard C, Mill J, Jeffries A (2020). In‐silico high throughput whole transcriptome screening implicates cardiovascular disease and the immune system in the mechanism of action underlying adverse effects of atypical antipsychotics. Alzheimer's & Dementia, 16(S9).
Ballard C, Kales HC, Lyketsos C, Aarsland D, Creese B, Mills R, Williams H, Sweet RA (2020). Psychosis in Alzheimer's Disease.
Curr Neurol Neurosci Rep,
20(12).
Abstract:
Psychosis in Alzheimer's Disease.
PURPOSE OF REVIEW: to review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). RECENT FINDINGS: Psychosis in Alzheimer's disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets.
Abstract.
Author URL.
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.
2019
Creese B, Ballard C, Vasconcelos Da Silva M (2019). Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer’s disease. Translational Psychiatry
Da Silva MV, Creese B, Johar I, Bergh S, Aarsland D, Rongve A, Medboen IT, Aakhus E, Andersen F, Braekhus A, et al (2019). O2‐11‐06: THE COURSE OF APATHY IN PEOPLE WITH DEMENTIA. Alzheimer's & Dementia, 15(7S_Part_11), p570-p570.
Da Silva MV, Creese B, Johar I, Aarsland D, Bergh S, Athanasiu L, Rongve A, Medboen IT, Aakhus E, Andersen F, et al (2019). P1‐131: GENOME WIDE ASSOCIATION STUDY: IDENTIFYING GENETIC MARKERS IN APATHY IN PEOPLE WITH ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 15(7S_Part_5), p286-p286.
Creese B, Brooker H, Wesnes K, Corbett A, Aarsland D, Ismail Z, Ballard C (2019). P1‐468: CHARACTERISING THE COGNITIVE PROFILE ASSOCIATED WITH INDIVIDUAL DOMAINS OF MID BEHAVIOURAL IMPAIRMENT IN THE COGNITIVELY NORMAL POPULATION. Alzheimer's & Dementia, 15(7S_Part_8), p447-p448.
Ballard C, Creese B, Chambers D, Williams G (2019). P2‐110: a NEURONAL CONNECTIVITY MAP (NMAP) DATABASE TO ESTABLISH a DRUG‐SCREENING PLATFORM FOR AD. Alzheimer's & Dementia, 15(7S_Part_12), p614-p614.
Johar I, Creese B, Bergh S, Athanasiu L, Medboen IT, Da Silva MV, Rongve A, Aakhus E, Anderson F, Bettella F, et al (2019). P2‐129: GENOME‐WIDE ASSOCIATION OF ALZHEIMER'S DISEASE WITH DYSPHORIA AND EVALUATION OF GENETIC OVERLAP WITH MAJOR DEPRESSIVE DISORDER. Alzheimer's & Dementia, 15(7S_Part_12), p621-p622.
Gatt A, Whitfield D, Creese B, Ballard C (2019). P3‐228: a MULTIPLEX BIOMARKER ASSAY FOR MEASURING TRANSCRIPTIONAL CHANGES IN THE 5XFAD MOUSE MODEL OF AD. Alzheimer's & Dementia, 15(7S_Part_19), p1019-p1019.
Creese B, Brooker H, Corbett A, Aarsland D, Ballard C (2019). P3‐319: FAMILY HISTORY OF DEMENTIA WITH PSYCHOTIC SYMPTOMS IN THE COGNITIVELY NORMAL POPULATION: FEASIBILITY OF MEASUREMENT AND INITIAL CLINICAL AND GENETIC ASSOCIATIONS. Alzheimer's & Dementia, 15(7S_Part_20), p1059-p1059.
Creese B, Brooker H, Corbett A, Ismail Z, Aarsland D, Ballard C (2019). P4‐248: EVALUATING SHARED GENETIC LIABILITY FOR LATE‐LIFE ABNORMAL THOUGHTS AND PERCEPTION (MILD BEHAVIORAL IMPAIRMENT), AND NEUROLOGICAL AND PSYCHIATRIC CONDITIONS. Alzheimer's & Dementia, 15(7S_Part_26), p1374-p1374.
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
Griffiths AW, Surr CA, Creese B, Garrod L, Chenoweth L (2019). The development and use of the assessment of dementia awareness and person-centred care training tool in long-term care.
Dementia (London),
18(7-8), 3059-3070.
Author URL.
Griffiths AW, Albertyn CP, Burnley NL, Creese B, Walwyn R, Holloway I, Safarikova J, Surr CA (2019). Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) tool - ERRATUM.
International Psychogeriatrics,
32(2), 287-287.
Abstract:
Validation of the Cohen-Mansfield Agitation Inventory Observational (CMAI-O) tool - ERRATUM
The above article (Griffiths et al. 2019) published with an incorrect abstract.The correct abstract is as follows:Objectives:Behaviours associated with agitation are common in people living with dementia. The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale widely used to assess agitation completed by a proxy (family carer or staff member). However, proxy informants introduce possible reporting bias when blinding to the treatment arm is not possible, and potential accuracy issues due to irregular contact between the proxy and the person with dementia over the reporting period. An observational measure completed by a blinded researcher may address these issues, but no agitation measures with comparable items exist.Design:Development and validation of an observational version of the CMAI (CMAI-O), to assess its validity as an alternative or complementary measure of agitation.Setting:Fifty care homes in England.Participants:Residents (N = 726) with dementia.Measurements:Two observational measures (CMAI-O and PAS) were completed by an independent researcher. Measures of agitation, functional status, and neuropsychiatric symptoms were completed with staff proxies.Results:The CMAI-O showed adequate internal consistency (α =. 61), criterion validity with the PAS (r =. 79, p = <. 001), incremental validity in predicting quality of life beyond the Functional Assessment Staging of Alzheimer’s disease (β = 1.83, p <. 001 at baseline) and discriminant validity from the Neuropsychiatric Inventory Apathy subscale (r =. 004, p =. 902).Conclusions:The CMAI-O is a promising research tool for independently measuring agitation in people with dementia in care homes. Its use alongside the CMAI could provide a more robust understanding of agitation amongst residents with dementia.
Abstract.
2018
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.
Creese B, Bell E, Johar I, Francis P, Ballard C, Aarsland D (2018). Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson's disease and Lewy body dementias: Review and meta-analyses.
Am J Med Genet B Neuropsychiatr Genet,
177(2), 232-241.
Abstract:
Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson's disease and Lewy body dementias: Review and meta-analyses.
Heterozygous mutations in glucocerebrosidase gene (GBA) are a major genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, there has been a considerable focus on the relationship between GBA mutations and emergence of cognitive impairment and neuropsychiatric symptoms in these diseases. Here, we review the literature in this area, with a particular focus, including meta-analysis, on the key neuropsychiatric symptoms of cognitive impairment, psychosis, and depression in Parkinson's disease. Our meta-analysis demonstrated that GBA mutations are associated with a 2.4-fold increased risk of cognitive impairment. In addition, our novel meta-analyses of psychosis and depression showed a 1.8- and 2.2-fold increased risk respectively associated with GBA mutations, although due to possible bias and heterogeneity the depression findings should be interpreted with caution. While the precise mechanisms which increase susceptibility to neurodegeneration in GBA carriers are not known, evidence of greater cortical Lewy body pathology, reduced patterns of cortical activation, and hippocampal pathology in animal models are all consistent with a direct effect of GBA mutations on these symptoms. Extension of this work in DLB and individuals without neurodegeneration will be important in further characterizing how GBA mutations increase risk for PD and DLB and influence disease course.
Abstract.
Author URL.
Surr C, Holloway I, Walwyn RE, Griffiths AW, Meads D, Kelley R, Martin A, McLellan V, Ballard C, Fossey J, et al (2018). O3‐08‐06: RESULTS OF a PRAGMATIC, CLUSTER RANDOMISED, CONTROLLED TRIAL OF THE EFFECTIVENESS AND COST‐EFFECTIVENESS OF DEMENTIA CARE MAPPING (DCM) IN UK CARE HOMES (DCM EPIC TRIAL). Alzheimer's & Dementia, 14(7S_Part_19), p1035-p1035.
Creese B, Bergh S, Aarsland D, Andersen F, Brooker H, Corbett A, Khan Z, Megalogeni M, Rongve A, Stordal E, et al (2018). P1‐151: GENETIC OVERLAP BETWEEN PSYCHOTIC SYMPTOMS ACROSS THE LIFESPAN: FINDINGS FROM SCHIZOPHRENIA, COGNITIVELY NORMAL OLDER ADULTS AND ALZHEIMER'S DISEASE. Alzheimer's & Dementia, 14(7S_Part_6).
Brooker H, Creese B, Ismail Z, Khan Z, Megalogeni M, Corbett A, Hampshire A, Aarsland D, Ballard C, Wesnes K, et al (2018). P1‐523: THE RELATIONSHIP BETWEEN THE MILD BEHAVIOURAL IMPAIRMENT CHECKLIST (MBI‐C) TOTAL SCORE AND CORE ASPECTS OF COGNITIVE FUNCTION IN OLDER ADULTS. Alzheimer's & Dementia, 14(7S_Part_9).
Creese B, Pishva E, Proitsi P, Smith RG, Ballard C, Hove DLA, Mill J, Lunnon K (2018). P2‐143: PSYCHOSIS‐ASSOCIATED EPIGENETIC VARIATION IN PATIENTS WITH ALZHEIMER'S DISEASE ACROSS CORTICAL BRAIN REGIONS. Alzheimer's & Dementia, 14(7S_Part_13), p723-p723.
Wesnes K, Brooker H, Creese B, Khan Z, Megalogeni M, Corbett A, Davis K, Hotopf M, Aarsland D, Ballard C, et al (2018). P2‐483: DEPRESSION IS ASSOCIATED WITH IMPAIRMENT IN COGNITIVE FUNCTION IN ADULTS AGED 50 AND OVER. Alzheimer's & Dementia, 14(7S_Part_16).
Creese B, Brooker H, Ismail Z, Aarsland D, Corbett A, Khan Z, Megalogeni M, Ballard C, Wesnes K (2018). P3‐554: PROFILE OF MILD BEHAVIOURAL IMPAIRMENT IN a POPULATION‐BASED SAMPLE OF ADULTS AGED 50 AND OVER: INITIAL FINDINGS FROM THE PROTECT STUDY. Alzheimer's & Dementia, 14(7S_Part_25).
Surr CA, Holloway I, Walwyn RE, Griffiths AW, Meads D, Kelley R, Martin A, Ballard C, Fossey J, Burnley N, et al (2018). The Clinical and Cost Effectiveness of Dementia Care Mapping (DCM™) to Reduce Agitation in Care Home Residents with Dementia: Results of the DCM™ EPIC Cluster Randomised Controlled Trial.
Creese B, Da Silva MV, Johar I, Ballard C (2018). The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.
Expert Rev Neurother,
18(6), 461-467.
Abstract:
The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.
Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions. Expert commentary: the current justification for antipsychotic use in the context of the changing landscape of prescribing and provide a view on the most promising alternative candidates to this class of drug are appraised.
Abstract.
Author URL.
2017
Aarsland D, Creese B, Chaudhuri KR (2017). A new tool to identify patients with Parkinson's disease at increased risk of dementia.
Lancet Neurol,
16(8), 576-578.
Author URL.
Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, Ballard C (2017). Cognitive decline in Parkinson disease.
Nat Rev Neurol,
13(4), 217-231.
Abstract:
Cognitive decline in Parkinson disease.
Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.
Abstract.
Author URL.
Ffytche DH, Creese B, Politis M, Chaudhuri KR, Weintraub D, Ballard C, Aarsland D (2017). The psychosis spectrum in Parkinson disease.
Nat Rev Neurol,
13(2), 81-95.
Abstract:
The psychosis spectrum in Parkinson disease.
In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors - for example, autonomic dysfunction - that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.
Abstract.
Author URL.
Creese B, Ballard C, Aarsland D, Bergh S, Rongve A, Selbaek G (2017). [P1–299]: AN EVALUATION OF PREDICTORS AND COGNITIVE DECLINE ASSOCIATED WITH PERSISTENT AND TRANSIENT PSYCHOTIC SYMPTOMS IN ALZHEIMER's DISEASE. Alzheimer's & Dementia, 13(7S_Part_7), p367-p367.
Johar I, Aarsland D, Ballard C, Bergh S, Fossey J, Kirkevold Ø, Medboen IT, Orrell M, Rongve A, Selbaek G, et al (2017). [P1–309]: PREVALENCE AND CO‐MORBIDITY OF APATHY AND DEPRESSION IN ALZHEIMER's DISEASE. Alzheimer's & Dementia, 13(7S_Part_7), p371-p372.
2016
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.
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.
Surr C, Lilley-Kelly A, Graham L, Walwyn R, Cicero R, Griffiths A, Creese B, Garrod L (2015). Complexities of trial recruitment in the care home setting: an illustration via the DCM™epic (dementia care mapping™: to enable person-centred care in care homes) trial. Trials, 16(Suppl 2).
2014
Creese B, Ballard C, Aarsland D, Londos E, Sharp S, Jones E (2014). Determining the Association of the 5HTTLPR Polymorphism with Delusions and Hallucinations in Lewy Body Dementias. The American Journal of Geriatric Psychiatry, 22(6), 580-586.
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.
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.
2013
Creese B, Ballard C, Jones E (2013). Cognitive Impairment in Studies of 5HTTLPR and Psychosis in Alzheimer’s Disease: a Systematic Review.
Dementia and Geriatric Cognitive Disorders,
35(3-4), 155-164.
Abstract:
Cognitive Impairment in Studies of 5HTTLPR and Psychosis in Alzheimer’s Disease: a Systematic Review
<b><i>Background/Aims:</i></b> Cognitive impairment is a well-established correlate of psychotic symptoms in Alzheimer’s disease (AD-P). We review whether this relationship has confounded previous genetic association studies of 5HTTLPR and AD-P. <b><i>Methods:</i></b> We reviewed all studies on 5HTTLPR and conducted a semi-quantitative analysis. <b><i>Results:</i></b> Three out of 4 studies with low MMSE reported a significant association, while 1 out of 4 with high MMSE reported a significant association. <b><i>Conclusions:</i></b> Variation in cognitive impairment in past studies has contributed to the inconsistency in findings. The findings presented here bring a greater clarity to our understanding of the role of 5HTTLPR in AD-P.
Abstract.
2012
Creese B, Ballard C, Aarsland D, Londos E, Sharp S, Jones E (2012). No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias. Neuroscience Letters, 531(1), 1-4.
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
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.