Abstract
. Objectives: to investigate using quantitative EEG (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer’s disease (MCI-AD) and (2) its utility as a potential biomarker for early differential diagnosis. Methods: We analyzed eyes-closed, resting state, high-density EEG data from highly phenotyped participants (39 MCI-LB, 36 MCI-AD, and 31 healthy controls). EEG measures included spectral power in different frequency bands (delta, theta, pre-alpha, alpha, and beta), theta/alpha ratio, dominant frequency, and dominant frequency variability. Receiver operating characteristics (ROC) analyses were performed to assess diagnostic accuracy. Results: There was a shift in power from beta and alpha frequency bands towards slower frequencies in the pre-alpha and theta range in MCI-LB compared to healthy controls. Additionally, dominant frequency was slower in MCI-LB compared to controls. We found significantly increased pre-alpha power, decreased beta power, and slower dominant frequency in MCI-LB compared to MCI-AD. EEG abnormalities were more apparent in MCI-LB cases with more diagnostic features. There were no significant differences between MCI-AD and controls. In the ROC analysis to distinguish MCI-LB from MCI-AD, beta power and dominant frequency showed the highest area under the curve values of 0.71 and 0.70, respectively. While specificity was high for some measures (up to 0.97 for alpha power and 0.94 for theta/alpha ratio), sensitivity was generally much lower. Conclusions: Early EEG slowing is a specific feature of MCI-LB compared to MCI-AD. However, there is overlap between the two MCI groups which makes it difficult to distinguish between them based on EEG alone.

OBJECTIVES: to explore the impact of COVID-19 on postdiagnostic dementia care and support provision in England and Wales. DESIGN: Qualitative research using semistructured interviews, via video or telephone conferencing. SETTING: Services providing postdiagnostic support across health, social care and the third sector. PARTICIPANTS: 21 professionals previously recruited to an ongoing research programme on postdiagnostic dementia care (or colleagues, if unavailable). RESULTS: Key themes identified from the data were: challenges caused by COVID-19; responses to those challenges, including a widespread shift to remote working; and effects of COVID-19 on future postdiagnostic support. Challenges included changing and sometimes conflicting guidelines; a lack of access to support; identifying and responding to emerging needs; emotional and physical impact of COVID-19; and balancing COVID-19 risk with other risks such as deterioration. Some dementia services closed, while others adapted and continued to provide support thus potentially widening existing inequalities. There were also some unintended positive outcomes, including improved cross-sector and multidisciplinary working between professionals. CONCLUSION: Delivering postdiagnostic dementia support during COVID-19 required essential adaptations. While some changes were detrimental to service users, others were identified as potentially beneficial and highly likely to become the new 'norm', for example, use of blended approaches, combining virtual and face-to-face work, thus allowing more flexible, integrated care. Our data have implications for policy and practice to improve the response to the lingering effects of COVID-19 as well as creating service provision that is more resilient to future pandemics or other periods of disruption.

Patients who have dementia with Lewy bodies and Alzheimer's disease show early degeneration of the cholinergic nucleus basalis of Meynert. However, how white matter projections between the nucleus basalis of Meynert and the cortex are altered in neurodegenerative disease is unknown. Tractography of white matter pathways originating from the nucleus basalis of Meynert was performed using diffusion-weighted imaging in 46 patients with Alzheimer's disease dementia, 48 with dementia with Lewy bodies, 35 with mild cognitive impairment with Alzheimer's disease, 38 with mild cognitive impairment with Lewy bodies and 71 control participants. Mean diffusivity of the resulting pathways was compared between groups and related to cognition, attention, functional EEG changes and dementia conversion in the mild cognitive impairment groups. We successfully tracked a medial and a lateral pathway from the nucleus basalis of Meynert. Mean diffusivity of the lateral pathway was higher in both dementia and mild cognitive impairment groups than controls (all P < 0.03). In the patient groups, increased mean diffusivity of this pathway was related to more impaired global cognition (β = -0.22, P = 0.06) and worse performance on an attention task (β = 0.30, P = 0.03). In patients with mild cognitive impairment, loss of integrity of both nucleus basalis of Meynert pathways was associated with increased risk of dementia progression [hazard ratio (95% confidence interval), medial pathway: 2.51 (1.24-5.09); lateral pathway: 2.54 (1.24-5.19)]. Nucleus basalis of Meynert volume was reduced in all clinical groups compared to controls (all P < 0.001), but contributed less strongly to cognitive impairment and was not associated with attention or dementia conversion. EEG slowing in the patient groups as assessed by a decrease in dominant frequency was associated with smaller nucleus basalis of Meynert volumes (β = 0.22, P = 0.02) and increased mean diffusivity of the lateral pathway (β = -0.47, P = 0.003). We show that degeneration of the cholinergic nucleus basalis of Meynert in Alzheimer's disease and dementia with Lewy bodies is accompanied by an early reduction in integrity of white matter projections that originate from this structure. This is more strongly associated with cognition and attention than the volume of the nucleus basalis of Meynert itself and might be an early indicator of increased risk of dementia conversion in people with mild cognitive impairment.

BACKGROUND: Higher continuity of GP care (CGPC), that is, consulting the same doctor consistently, can improve doctor-patient relationships and increase quality of care; however, its effects on patients with dementia are mostly unknown. AIM: to estimate the associations between CGPC and potentially inappropriate prescribing (PIP), and with the incidence of adverse health outcomes (AHOs) in patients with dementia. DESIGN AND SETTING: a retrospective cohort study with 1 year of follow-up anonymised medical records from 9324 patients with dementia, aged ≥65 years living in England in 2016. METHOD: CGPC measures include the Usual Provider of Care (UPC), Bice-Boxerman Continuity of Care (BB), and Sequential Continuity (SECON) indices. Regression models estimated associations with PIPs and survival analysis with incidence of AHOs during the follow-up adjusted for age, sex, deprivation level, 14 comorbidities, and frailty. RESULTS: the highest quartile (HQ) of UPC (highest continuity) had 34.8% less risk of delirium (odds ratio [OR] 0.65, 95% confidence interval [CI] = 0.51 to 0.84), 57.9% less risk of incontinence (OR 0.42, 95% CI = 0.31 to 0.58), and 9.7% less risk of emergency admissions to hospital (OR 0.90, 95% CI = 0.82 to 0.99) compared with the lowest quartile. Polypharmacy and PIP were identified in 81.6% (n = 7612) and 75.4% (n = 7027) of patients, respectively. The HQ had fewer prescribed medications (HQ: mean 8.5, lowest quartile (LQ): mean 9.7, P

BACKGROUND: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years. METHOD: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory. RESULTS: of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement. CONCLUSIONS: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution.

OBJECTIVE: to assess the accuracy of documentation of the symptoms and diagnosis of delirium in medical notes of inpatients with Parkinson's disease (PD). METHODS: the DETERMINE-PD pilot study assessed PD inpatients over 4-months. Delirium prevalence was classified prospectively using a standardized assessment at a single visit on the basis of Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria. Incident delirium was diagnosed retrospectively using detailed clinical vignettes and validated consensus method. Inpatient medical notes and discharge summaries of those with delirium were reviewed for documentation of symptoms, diagnosis and follow-up. RESULTS: Forty-four PD patients consented to take part in the study, accounting for 53 admissions. We identified 30 cases (56.6%) of delirium during the participants' stay in hospital. of those with delirium identified by the research team, delirium symptoms were documented in the clinical notes of 72.3%; 37.9% had a delirium diagnosis documented. Older patients were more likely to have delirium (p = 0.027) and have this diagnosis documented (p = 0.034). Time from documentation of symptoms to diagnosis ranged from

This qualitative study was designed to understand the impact of social distancing measures on people with dementia and carers living in the community in England and Wales during a period of social restrictions before the COVID-19 vaccination roll-out. We conducted 12 semi-structured interviews with people with dementia aged 50-88 years, living alone or with a partner, and 10 carers aged 61-78 years, all living with the person with dementia. Three of the interviews were with dyads. Participants were recruited during November and December 2020. We used framework analysis to identify themes and elicit suggestions for potential solutions. We identified three interrelated themes. People with dementia experienced a fear of decline in capabilities or mood and attempted to mitigate this. Carers noticed changes in the person with dementia and increased caring responsibilities, and for some, a change in the relationship. Subsequently, reduced confidence in capabilities to navigate a new and hostile environment created a cyclical dilemma of re-engaging where an inability to access usual activities made things worse. People with dementia and carers experienced neglect and being alone in their struggle, alongside feeling socially excluded during the pandemic, and there was little optimism associated with the upcoming vaccine programme. People found their own solutions to reduce the effects of isolation by keeping busy and being socially active, and practising skills deemed to help reduce the progression of dementia. This and some limited local public initiatives for the general public facilitated feelings of social inclusion. This study adds understanding to existing evidence about the longer-term experience of social isolation several months into the pandemic. It highlights the importance of health and community groups and suggests how services can find ways to support, include, and interact with people with dementia and carers during and after social restrictions.

BACKGROUND: National audits are a common, but variably effective, intervention to improve services. This study aimed to design an intervention to increase the effectiveness of national audit. METHODS: We used interviews, documentary analysis, observations, co-design and stakeholder engagement methods. The intervention was described in an intervention manual and illustrated using a logic model. Phase 1 described the current hospital response to a national audit. Phase 2 identified potential enhancements. Phase 3 developed a strategy to implement the enhancements. Phase 4 explored the feasibility of the intervention alongside the National Audit of Dementia and refined the intervention. Phase 5 adapted the intervention to a second national audit (National Diabetes Audit). Phase 6 explored the feasibility and fidelity of the intervention alongside the National Diabetes Audit and used the findings to further refine the intervention. RESULTS: the developed intervention is a quality improvement collaborative (QIC), containing virtual educational workshop, virtual outreach for local team leads and virtual facilitation of a learning collaborative delivered after feedback has been received. The QIC aims to support national audit recipients to undertake improvement actions tailored to their local context. The target audience is clinical and clinical governance leaders. We found that actions from national audit were constrained by what the clinical lead perceived they deliver personally, these actions were not aligned to identified influences upon performance. We found that the hospital response could be enhanced by targeting low baseline performance, identifying and addressing influences upon to performance, developing trust and credibility, addressing recipient priorities, presenting meaningful comparisons, developing a conceptual model, involving stakeholders and considering the opportunity cost. Phase 3 found that an educational workshop and outreach strategy could support implementation of the enhancements through developing coherence and cognitive participation. We found feasibility could be increased by revising the content, re-naming the intervention, amending activities to address time commitment, incorporating a more structured analysis of influences, supporting collaboration and developing local feedback mechanisms. Phase 5 found adaptation to a second national audit involved reflecting differences in the clinical topic, context and contractual requirements. We found that the behaviour change techniques identified in the manual were delivered by facilitators. Participants reported positive attitudes towards the intervention and that the intervention was appropriate. CONCLUSIONS: the QIC supports local teams to tailor their actions to local context and develop change commitment. Future work will evaluate the effectiveness of the intervention as an adjunct to the National Diabetes Audit.

BACKGROUND: Delirium is a serious acute neuropsychiatric condition associated with altered attention and arousal. OBJECTIVE: to evaluate simple bedside tests for attention and arousal to detect delirium in those with and without Parkinson's disease (PD) and dementia. METHODS: Participants from two prospective delirium studies were pooled comprising 30 with PD without cognitive impairment, 24 with Lewy body cognitive impairment (PD dementia or dementia with Lewy bodies), 16 with another dementia and 179 PD and dementia-free older adults. Participants completed standardised delirium assessments including tests of attention: digit span, Memorial Delirium Assessment Scale (MDAS) attention and months of the year backwards; and arousal: Glasgow Coma Scale (GSC), Observational Scale of Level of Arousal (OSLA), Modified Richmond Agitation Scale and MDAS consciousness. Delirium was diagnosed using the DSM-5 criteria. RESULTS: on their first admission, 21.7%participants had prevalent delirium. Arousal measures accurately detected delirium in all participants (p 

Stroke events increase the risk of developing dementia, 10% for a first-ever stroke and 30% for recurrent strokes. However, the effects of stroke on global cognition, leading up to dementia, remain poorly understood. We investigated: (i) post-stroke trajectories of cognitive change, (ii) trajectories of cognitive decline in those who develop dementia over periods of follow-up length and (iii) risk factors precipitating the onset of dementia. Prospective cohort of hospital-based stroke survivors in North-East England was followed for up to 12 years. In this study, we included 355 stroke survivors of ≥75 years of age, not demented 3 months post-stroke, who had had annual assessments during follow-up. Global cognition was measured annually and characterized using standardized tests: Cambridge Cognition Examination-Revised and Mini-Mental State Examination. Demographic data and risk factors were recorded at baseline. Mixed-effects models were used to study trajectories in global cognition, and logistic models to test associations between the onset of dementia and key risk factors, adjusted for age and sex. of the 355 participants, 91 (25.6%) developed dementia during follow-up. The dementia group had a sharper decline in Cambridge Cognition Examination-Revised (coeff. = -1.91, 95% confidence interval = -2.23 to -1.59, P 

INTRODUCTION: the increasingly ageing population is associated with greater numbers of people living with dementia (PLwD) and mild cognitive impairment (MCI). There are an estimated 55 million PLwD and approximately 6% of people over 60 years of age are living with MCI, with the figure rising to 25% for those aged between 80 and 84 years. Sleep disturbances are common for this population, but there is currently no standardised approach within UK primary care to manage this. Coined as a 'wicked design problem', sleep disturbances in this population are complex, with interventions supporting best management in context. METHODS AND ANALYSIS: the aim of this realist review is to deepen our understanding of what is considered 'sleep disturbance' in PLwD or MCI within primary care. Specifically, we endeavour to better understand how sleep disturbance is assessed, diagnosed and managed. To co-produce this protocol and review, we have recruited a stakeholder group comprising individuals with lived experience of dementia or MCI, primary healthcare staff and sleep experts. This review will be conducted in line with Pawson's five stages including the development of our initial programme theory, literature searches and the refinement of theory. The Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) quality and reporting standards will also be followed. The realist review will be an iterative process and our initial realist programme theory will be tested and refined in response to our data searches and stakeholder discussions. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. We will follow the RAMESES standards to ensure we produce a complete and transparent report. Our final programme theory will help us to devise a tailored sleep management tool for primary healthcare professionals, PLwD and their carers. Our dissemination strategy will include lay summaries via email and our research website, peer-reviewed publications and social media posts. PROSPERO REGISTRATION NUMBER: CRD42022304679.

OBJECTIVE: to provide evidence that cardiac I-123-metaiodobenzylguanidine sympathetic innervation imaging (MIBG) scintigraphy differentiates probable mild cognitive impairment with Lewy bodies (MCI-LB) from mild cognitive impairment due to Alzheimer disease (MCI-AD), we scanned patients with MCI and obtained consensus clinical diagnoses of their MCI subtype. We also performed baseline FP-CIT scans to compare the accuracy of MIBG and FP-CIT. METHODS: We conducted a prospective cohort study into the accuracy of cardiac MIBG scintigraphy in the diagnosis of MCI-LB. Follow-up clinical assessment was used to diagnose MCI-AD (no core features of MCI-LB and normal FP-CIT), probable MCI-LB (2 or more core features, or 1 core feature with abnormal FP-CIT), or possible MCI-LB (1 core feature or abnormal FP-CIT). For the comparison between MIBG and FP-CIT, only core clinical features were used for diagnosis. RESULTS: We recruited 95 people with mild cognitive impairment. Cardiac MIBG was abnormal in 22/37 probable and 2/15 possible MCI-LB cases and normal in 38/43 MCI-AD cases. The sensitivity in probable MCI-LB was 59% (95% confidence interval [CI], 42%-75%), specificity 88% (75%-96%), and accuracy 75% (64%-84%). The positive likelihood ratio was 5.1 and negative likelihood ratio 0.46. With symptom-only diagnoses, the accuracies were 79% for MIBG (95% CI, 68%-87%) and 76% for FP-CIT (95% CI, 65%-85%). CONCLUSIONS: Cardiac MIBG appears useful in early disease, with an abnormal scan highly suggestive of MCI-LB. Validation in a multicenter setting is justified. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cardiac MIBG distinguishes MCI-LB from MCI-AD.

BACKGROUND: People living with all stages of dementia should have the opportunity to participate in meaningful occupations. For those living in care homes, this may not always occur and residents may spend significant parts of the day unengaged, especially those living with more advanced dementia. Digital technologies are increasingly being used in health care and could provide opportunities for people living with dementia (PLWD) in care homes to engage in meaningful occupations and support care staff to provide these activities. With technology advancing at a rapid rate, the objective of this scoping review is to provide an up-to-date systematic map of the research on the diverse range of digital technologies that support engagement in meaningful occupations. In particular, focus will be given to barriers and facilitators to inform future intervention design and implementation strategies, which have not yet been clearly mapped across the full range of these digital technologies. METHOD: a scoping review will be conducted to systematically search for published research using a comprehensive search strategy on thirteen databases. Published, peer-reviewed studies that focused on PLWD in the care home setting and assessed any form of digital technology that supported a meaningful occupation will be included. All methodologies which meet the criteria will be included. Data will be extracted and charted to report the range of digital technologies, underlying mechanisms of action, facilitators and barriers to implementation. DISCUSSION: Mapping the range of technologies to support PLWD to engage in meaningful occupations will identify gaps in research. The systematic search will include a diverse range of technologies such as software to enhance care planning, tablets devices, smartphones, communication robots and social media platforms, rather than focussing on a specific design or interface. This will enable comparison between mechanisms of action, barriers and facilitators to implementation which will be useful for future research and intervention design. TRIAL REGISTRATION: Open Science Framework https://doi.org/10.17605/OSF.IO/7UDM2.

Previous resting-state fMRI studies in dementia with Lewy bodies have described changes in functional connectivity in networks related to cognition, motor function, and attention as well as alterations in connectivity dynamics. However, whether these changes occur early in the course of the disease and are already evident at the stage of mild cognitive impairment is not clear. We studied resting-state fMRI data from 31 patients with mild cognitive impairment with Lewy bodies compared to 28 patients with mild cognitive impairment due to Alzheimer's disease and 24 age-matched controls. We compared the groups with respect to within- and between-network functional connectivity. Additionally, we applied two different approaches to study dynamic functional connectivity (sliding-window analysis and leading eigenvector dynamic analysis). We did not find any significant changes in the mild cognitive impairment groups compared to controls and no differences between the two mild cognitive impairment groups, using static as well as dynamic connectivity measures. While patients with mild cognitive impairment with Lewy bodies already show clear functional abnormalities on EEG measures, the fMRI analyses presented here do not appear to be sensitive enough to detect such early and subtle changes in brain function in these patients.

Background
Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson’s disease dementia, is the second commonest cause of neurodegenerative dementia. Existing evidence suggests that it is underdiagnosed and without a consistent approach to management.

Objectives
To improve the diagnosis and management of Lewy body dementia by (1) understanding current diagnostic practice for dementia with Lewy bodies and Parkinson’s disease dementia; (2) identifying barriers to and facilitators of diagnosis and management; (3) developing evidence-based assessment toolkits to improve diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia; (4) producing a management toolkit to facilitate management; and (5) undertaking a pilot cluster randomised clinical trial.

Design
Work package 1 assessed clinical diagnostic rates from case notes for dementia with Lewy bodies and Parkinson’s disease dementia before and after (work package 1 repeated) introduction of an assessment toolkit. In work package 2, we developed a management toolkit for Lewy body dementia. In work package 3, we developed assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia and piloted these and the management toolkit in a clinical service. In work package 4, we undertook a pilot study of 23 services in nine NHS trusts that were cluster randomised to receiving and using the management toolkit or standard care. Work package 5 comprised a series of qualitative studies, examining barriers to and facilitators of diagnosis and management.

Setting
Secondary care memory assessment and movement disorder services in England.

Interventions
Assessment toolkits for Lewy body dementia consisted of questions for diagnostic symptoms, and management toolkits comprised 161 guidance statements grouped under five symptom domains.

Review methods
The systematic reviews of pharmacological and non-pharmacological management were based on published literature, with meta-analysis when possible, following a search of several electronic databases and the grey literature using terms related to Lewy body dementia, without restriction on time or language.

Participants
Participants aged ≥ 50 years diagnosed with dementia with Lewy bodies or Parkinson’s disease dementia and, for work package 1 and work package 1 repeated, non-dementia with Lewy bodies and non-Parkinson’s disease dementia controls. The qualitative studies included people with Lewy body dementia, carers and professionals.

Main outcome measures
For work packages 1 and 1 repeated, diagnostic rates for dementia with Lewy bodies and Parkinson’s disease dementia as a proportion of all dementia or Parkinson’s disease. For work packages 2 and 3, the production of diagnostic and management toolkits. For work package 4, feasibility of undertaking a cluster randomised trial of the toolkits, measured by number of participants recruited and use of the toolkits, assessed qualitatively.

Results
Work package 1 – 4.6% of dementia cases in secondary care received a dementia with Lewy bodies diagnosis (with significant differences in diagnostic rates between services) and 9.7% of those with Parkinson’s disease had a diagnosis of Parkinson’s disease dementia. There was evidence of delays in diagnosis for both dementia with Lewy bodies and Parkinson’s disease dementia compared with control patients, and the costs of dementia with Lewy bodies and Parkinson’s disease dementia were also greater than those for matched controls (p  80% were retained in the study at 6 months. Work package 5 – barriers to diagnosis and management of Lewy body dementia were complex. Managing Lewy body dementia often requires input from a range of specialties and, therefore, care pathways may be fragmented. Positive attitudes to diagnosing Lewy body dementia, working with a team with expertise in Lewy body dementia and opportunities for cross-specialty discussion of patients with complex needs facilitated diagnosis and management. The toolkits were generally well received, particularly the management toolkit. Implementation, however, varied, reflecting differences in attitudes, skills, time and local leadership. Work package 1 repeated – following introduction of the assessment toolkit, we found that 9.7% of dementia cases had dementia with Lewy bodies (a significant increase from baseline; p = 0.0019), but Parkinson’s disease dementia rates were similar (8.2%) to baseline.

Limitations
We included only two geographical regions and evidence informing the management toolkit was limited. Work package 4 was a pilot study and, therefore, we did not set out to assess the extent to which use of the management toolkit altered outcomes at the individual patient level. We noted implementation of the toolkits was variable. The increase in diagnostic rates in dementia with Lewy bodies following introduction of the assessment toolkits cannot be necessarily causally attributed to them.

Conclusions
Dementia with Lewy bodies and Parkinson’s disease dementia were diagnosed in secondary care NHS services, with a lower frequency (around half) than that expected from known prevalence rates. The introduction of assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia was associated with increased diagnostic rates of dementia with Lewy bodies, but not Parkinson’s disease dementia. Qualitative studies indicated inherent complexities of the disease itself, with treatment requiring input from different specialties and the potential for fragmented services, a workforce with variable training and confidence in Lewy body dementia, and negative attitudes towards diagnosis. The cluster randomised pilot trial demonstrated that patients could be successfully recruited, and provided preliminary evidence that the toolkits could be implemented in clinical services.

Future work
The evidence base informing the management of Lewy body dementia is limited, especially for non-pharmacological interventions. More well-designed randomised controlled trials for both cognitive and non-cognitive symptoms are needed.

Trial registration
Current Controlled Trials ISRCTN11083027.

Objectives: to investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. Methods: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. Results: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. Conclusions: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group.

BackgroundThere has been a shift in focus of international dementia policies from improving diagnostic rates to enhancing the post-diagnostic support provided to people with dementia and their carers. There is, however, little agreement over what constitutes good post-diagnostic support. This study aimed to identify the components of post-diagnostic dementia support.MethodsWe adopted a qualitative design using interviews, focus groups and observation to explore the perspectives of key stakeholders on the content of post-diagnostic dementia support. Purposive sampling was used to identify sites in England and Wales recognised as delivering good practice. Participants included 17 people with dementia, 31 carers, 68 service managers or funders, and 78 frontline staff. Interviews and focus groups were audio recorded and transcribed for analysis. Forty-eight sessions of observation were completed and recorded in fieldnotes. Components were identified through an inductive, thematic approach and cross-checked against national guidelines and existing frameworks; they were subsequently critically reviewed by a range of experts and our mixed stakeholder panel.ResultsTwenty distinct components of post-diagnostic support were identified, related to five themes: timely identification and management of needs; understanding and managing dementia; emotional and psychological wellbeing; practical support; and integrating support. The first and last of these were cross-cutting themes facilitating the delivery of a unique constellation of components of post-diagnostic support to each individual living with dementia or dyad at a particular time.ConclusionsOur work offers an empirically based framework to inform the development and delivery of holistic, integrated and continuous dementia care from diagnosis to end of life. It highlights the relevance of many components to both people living with dementia and their carers. Since the framework was developed in England and Wales, further research is needed to explore the relevance of our components to other sectors, countries and care systems.

BACKGROUND: Hospitals in many countries are encouraged to develop audits to assess and improve the quality of care. Ward audit is a specific form of audit and feedback that is commonly used but little studied. The aim of this study is to describe the content and application of hospital ward audit in order to identify potential enhancements to such audits. METHODS: Multiple qualitative methods were used to study a diversity sample of four English National Health Service organisations over a 16-month period. We undertook semi-structured interviews (n = 32), documentary analysis (n = 44) and 25 h of observations of healthcare workers involved in the design and implementation of ward audit. Data were analysed using framework analysis. Findings were presented iteratively to stakeholders who used them to develop a description of the content and delivery of ward audit. RESULTS: Ward audit consisted of seven stages: impetus; method; preparation of staff; assessing practice; analysis; feedback; and decide on action to improve. Two key stages were the monthly assessment of practice using case note data extraction, and the resulting feedback to clinical staff, ward managers, matrons and directors of nursing. At three organisations, the case note data were extracted by staff and there was evidence that this resulted in misrepresentation of the clinical performance audited. The misrepresentation appeared to be associated with the anticipation of punitive feedback from directors of nursing and matrons, as well as time pressures and a lack clarity about the method of audit data collection. Punitive feedback was reported to occur if no data were collected, if data demonstrated poor performance or if performance did not improve. CONCLUSIONS: Organisations invest considerable clinical resources in ward audit, but such audits may have unintended, potentially negative, consequences due to the impacts from punitive feedback. We discuss potential enhancements to ward audit (e.g. providing feedback recipients with suggested actions for improvement) and discuss implications for theory. There is a need to reduce the use of punitive feedback.

IMPORTANCE: treatment of dementia in individuals with comorbidities is complex, leading to potentially inappropriate prescribing (PIP). The impact of PIP in this population is unknown. OBJECTIVE: to estimate the rate of PIP and its effect on adverse health outcomes (AHO). DESIGN: retrospective cohort. SETTING: primary care electronic health records linked to hospital discharge data from England. SUBJECTS: 11,175 individuals with dementia aged over 65 years in 2016 and 43,463 age- and sex-matched controls. METHODS: Screening Tool of Older Persons' Prescriptions V2 defined PIP. Logistic regression tested associations with comorbidities at baseline, and survival analyses risk of incident AHO, adjusted for age, gender, deprivation and 14 comorbidities. RESULTS: the dementia group had increased risk of PIP (73% prevalence; odds ratio [OR]: 1.92; confidence interval [CI]: 83-103%; P 

BACKGROUND: Global policy recommendations suggest a task-shifted model of post-diagnostic dementia care, moving towards primary and community-based care. It is unclear how this may best be delivered. AIM: to assess the effectiveness and cost-effectiveness of primary care-based models of post-diagnostic dementia care. DESIGN AND SETTING: a systematic review of trials and economic evaluations of post-diagnostic dementia care interventions where primary care was substantially involved in care plan decision making. METHOD: Searches were undertaken of MEDLINE, PsychINFO, EMBASE, Web of Science, and CINAHL (from inception to March 2019). Two authors independently critically appraised studies and inductively classified interventions into types of care models. Random effects meta-analysis or narrative synthesis was conducted for each model where appropriate. RESULTS: from 4506 unique references and 357 full texts, 23 papers were included from 10 trials of nine interventions, delivered in four countries. Four types of care models were identified. Primary care provider (PCP)-led care (n = 1) led to better caregiver mental health and reduced hospital and memory clinic costs compared with memory clinics. PCP-led care with specialist consulting support (n = 2) did not have additional effects on clinical outcomes or costs over usual primary care. PCP-case management partnership models (n = 6) offered the most promise, with impact on neuropsychiatric symptoms, caregiver burden, distress and mastery, and healthcare costs. Integrated primary care memory clinics (n = 1) had limited evidence for improved quality of life and cost-effectiveness compared with memory clinics. CONCLUSION: Partnership models may impact on some clinical outcomes and healthcare costs. More rigorous evaluation of promising primary care-led care models is needed.

Dementia with Lewy bodies and Parkinson's disease dementia, jointly known as Lewy body dementia, are common neurodegenerative conditions. Patients with Lewy body dementia present with a wide range of cognitive, neuropsychiatric, sleep, motor, and autonomic symptoms. Presentation varies between patients and can vary over time within an individual. Treatments can address one symptom but worsen another, which makes disease management difficult. Symptoms are often managed in isolation and by different specialists, which makes high-quality care difficult to accomplish. Clinical trials and meta-analyses now provide an evidence base for the treatment of cognitive, neuropsychiatric, and motor symptoms in patients with Lewy body dementia. Furthermore, consensus opinion from experts supports the application of treatments for related conditions, such as Parkinson's disease, for the management of common symptoms (eg, autonomic dysfunction) in patients with Lewy body dementia. However, evidence gaps remain and future clinical trials need to focus on the treatment of symptoms specific to patients with Lewy body dementia.

Objectives: to investigate using quantitative EEG the (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer's disease (MCI-AD) and (2) its utility as a potential biomarker for early differential diagnosis. Methods: We analyzed eyes-closed, resting-state, high-density EEG data from highly phenotyped participants (39 MCI-LB, 36 MCI-AD, and 31 healthy controls). EEG measures included spectral power in different frequency bands (delta, theta, pre-alpha, alpha, and beta), theta/alpha ratio, dominant frequency, and dominant frequency variability. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. Results: There was a shift in power from beta and alpha frequency bands towards slower frequencies in the pre-alpha and theta range in MCI-LB compared to healthy controls. Additionally, the dominant frequency was slower in MCI-LB compared to controls. We found significantly increased pre-alpha power, decreased beta power, and slower dominant frequency in MCI-LB compared to MCI-AD. EEG abnormalities were more apparent in MCI-LB cases with more diagnostic features. There were no significant differences between MCI-AD and controls. In the ROC analysis to distinguish MCI-LB from MCI-AD, beta power and dominant frequency showed the highest area under the curve values of 0.71 and 0.70, respectively. While specificity was high for some measures (up to 0.97 for alpha power and 0.94 for theta/alpha ratio), sensitivity was generally much lower. Conclusions: Early EEG slowing is a specific feature of MCI-LB compared to MCI-AD. However, there is an overlap between the two MCI groups which makes it difficult to distinguish between them based on EEG alone.

BACKGROUND: Fall-related injuries are a significant cause of morbidity and mortality in people with dementia. There is presently little evidence to guide the management of such injuries, and yet there are potentially substantial benefits to be gained if the outcomes of these injuries could be improved. This study aimed to design an appropriate new health-care intervention for people with dementia following a fall and to assess the feasibility of its delivery in the UK NHS. OBJECTIVES: to determine whether or not it is possible to design an intervention to improve outcomes of falls in dementia, to investigate the feasibility and acceptability of the DIFRID (Developing an Intervention for Fall related Injuries in Dementia) intervention and to investigate the feasibility of a future randomised controlled trial and the data collection tools needed to evaluate both the effectiveness and the cost-effectiveness of the DIFRID intervention. DESIGN: This was a mixed-methods feasibility study. A systematic review (using Cochrane methodology) and realist review [using Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) methodology] explored the existing evidence base and developed programme theories. Searches were carried out in November 2015 (updated in January 2018) for effectiveness studies and in August 2016 for economic studies. A prospective observational study identified service use via participant diary completion. Qualitative methods (semistructured interviews, focus groups and observation) were used to explore current practice, stakeholder perspectives of the health and social care needs of people with dementia following a fall, ideas for intervention and barriers to and facilitators of change. Each of the resulting data sets informed intervention development via Delphi consensus methods. Finally, a single-arm feasibility study with embedded process evaluation was conducted. SETTING: This study was set in the community. PARTICIPANTS: the participants were (1) people with dementia presenting with falls necessitating health-care attention in each setting (primary care, the community and secondary care) at three sites and their carers, (2) professionals delivering the intervention, who were responsible for training and supervision and who were members of the intervention team, (3) professionals responsible for approaching and recruiting participants and (4) carers of participants with dementia. INTERVENTIONS: This was a complex multidisciplinary therapy intervention. Physiotherapists, occupational therapists and support workers delivered up to 22 sessions of tailored activities in the home or local area of the person with dementia over a period of 12 weeks. MAIN OUTCOME MEASURES: (1) Assessment of feasibility of study procedures; (2) assessment of the acceptability, feasibility and fidelity of intervention components; and (3) assessment of the suitability and acceptability of outcome measures for people with dementia and their carers (number of falls, quality of life, fear of falling, activities of daily living, goal-setting, health-care utilisation and carer burden). RESULTS: a multidisciplinary intervention delivered in the homes of people with dementia was designed based on qualitative work, realist review and recommendations of the consensus panel. The intervention was delivered to 11 people with dementia. The study suggested that the intervention is both feasible and acceptable to stakeholders. A number of modifications were recommended to address some of the issues arising during feasibility testing. The measurement of outcome measures was successful. CONCLUSIONS: the study has highlighted the feasibility of delivering a creative, tailored, individual approach to intervention for people with dementia following a fall. Although the intervention required greater investment of time than usual practice, many staff valued the opportunity to work more closely with people with dementia and their carers. We conclude that further research is now needed to refine this intervention in the context of a pilot randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41760734 and PROSPERO CRD42016029565. 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. 23, No. 59. See the NIHR Journals Library website for further project information.

AIMS: Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE). METHODS: Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3 h) or full-time (Full) exposure to EE per day for 12 weeks. RESULTS: High frequencies of moderate carotid artery stenosis (51-75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P 50% in BCAS mice exposed to EE compared with BCAS-Std (P 

Objectives: People with dementia are more likely to fall and less likely to recover well after a fall than cognitively intact older people. Little is known about how best to deliver services to this patient group. This paper explores the importance of compensating for cognitive impairment when working with people with dementia. Methods: Qualitative methods - interviews, focus groups and observation - were used to explore the views and experiences of people with dementia, family carers and professionals providing services to people with dementia following an injurious fall. A thematic, iterative analysis was undertaken in which emerging themes were identified from each individual dataset, prior to an integrative analysis. Results: a key theme across all datasets was the need to deliver services in ways that compensate for cognitive impairment, such as negotiating meaningful activities that can be embedded into the routines of people with dementia. Professionals varied in their ability to adapt their practice to meet the needs of people with dementia. Negative attitudes towards dementia, a lack of knowledge and understanding of dementia limited the ability of some professionals to work in person-centred ways. Conclusion: Improving outcomes for people with dementia following a fall requires the principles of person-centred care to be enacted by professionals with a generic role, as well as specialist staff. This requires additional training and support by specialist staff to address the wide variability in current practice.

INTRODUCTION: multiple conditions in later life (multi-morbidity) is a major challenge for health and care systems worldwide, is of particular relevance for older people, but has not (until recently) received high priority as a topic for research. We have identified the top 10 research priorities from the perspective of older people, their carers, and health and social care professionals using the methods of a James Lind Alliance Priority Setting Partnership. METHODS: in total, 354 participants (162 older people and carers, 192 health professionals) completed a survey and 15 older people and carers were interviewed to produce 96 'unanswered questions'. These were further refined by survey and interviews to a shortlist of 21 topics, and a mix of people aged 80+ living with three or more conditions, carers and health and social care providers to prioritised the top 10. RESULTS: the key priorities were about the prevention of social isolation, the promotion of independence and physical and emotional well-being. In addition to these broad topics, the process also identified detailed priorities including the role of exercise therapy, the importance of falls (particularly fear of falling), the recognition and management of frailty and Comprehensive Geriatric Assessment. CONCLUSION: these topics provide a unique perspective on research priorities on multiple conditions in later life and complement existing UK and International recommendations about the optimisation of health and social care systems to deliver essential holistic models of care and the prevention and treatment of multiple co-existing conditions.

INTRODUCTION: people with dementia are more likely to fall and less likely to recover well after a fall than cognitively intact older people. Little is known about how best to deliver services to this patient group. This paper explored current service provision to help inform the development of a new intervention. METHODS: qualitative approaches were used to explore the views and experiences of people with dementia, family carers and professionals providing services to people with dementia following an injurious fall. These data were analysed using a thematic, iterative analysis. FINDINGS: while a wide range of services potentially relevant to people with dementia was identified, there were no dedicated services for people with dementia with fall-related injuries in our three geographical areas. Factors influencing service uptake included a lack of knowledge of local provision amongst professionals and underdeveloped information sharing systems. Some aspects of current service organisation were incompatible with the needs of people with dementia. These include an emphasis on time-limited interventions; lack of longer-term follow-up; and service delivery in environments that could be challenging for people with dementia. CONCLUSIONS: care pathways for people with dementia who fall are fragmented and unclear. This is likely to preclude people with dementia from receiving all appropriate support and contribute to poor recovery following a fall. The findings highlight the need for new approaches to service organisation and delivery which address the specific needs of people with dementia who fall.

BACKGROUND: the annual prevalence of falls in people with dementia ranges from 47 to 90%. Falls are a common reason for hospital admission in people with dementia, and there is limited research evidence regarding the care pathways experienced by this population. In addition to immediate management of an injury, prevention of further falls is likely to be an important part of any successful intervention. This review aims to assess the effectiveness of interventions for improving the physical and psychological wellbeing of people with dementia who have sustained a fall-related injury. METHODS: Systematic review methodologies were employed utilising searches across multiple databases (MEDLINE, CENTRAL, Health Management Information Consortium, EMBASE, CINAHL, Web of Science, Allied and Complementary Medicine Database, and Physiotherapy Evidence Database (PEDro)) and citation chaining. Studies including people with a known diagnosis of dementia living in the community and who present at health services with a fall, with or without injury, were included. Outcomes of interest included mobility, recurrent falls, activities of daily living, length of hospital stay, and post-discharge residence. Results were independently reviewed and quality assessed by two researchers, and data extracted using a customised form. A narrative synthesis was performed due to heterogeneity of the included studies. RESULTS: Seven studies were included. Interventions clustered into three broad categories: multidisciplinary in-hospital post-surgical geriatric assessment; pharmaceuticals; and multifactorial assessment. Multidisciplinary care and early mobilisation showed short-term improvements for some outcomes. Only an annual administration of zoledronic acid showed long-term reduction in recurrent falls. CONCLUSIONS: Due to high heterogeneity across the studies, definitive conclusions could not be reached. Most post-fall interventions were not aimed at patients with dementia and have shown little efficacy regardless of cognitive status. Minor improvements to some quality of life indicators were shown, but these were generally not statistically significant. Conclusions were also limited due to most studies addressing hip fracture; the interventions provided for this type of injury may not be suitable for other types of fractures or soft tissue injuries, or for use in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016029565.

BACKGROUND: People with dementia (PWD) experience ten times as many incident falls as people without dementia. Little is known about how best to deliver services to people with dementia following a fall. We used an integrated, mixed-methods approach to develop a new intervention which combines theory generated via a realist synthesis and data on current provision and pathways, gathered through a prospective observational study as well as qualitative interviews, focus groups and ethnographic observation. This intervention is to be tested in a feasibility study in the UK National Health Service. METHODS: People living with dementia in one of three geographical areas will be eligible for the study if they experience a fall requiring healthcare attention and have an informal carer. Potential participants will be identified by community services (primary care, paramedics, telecare), secondary care (ED, facilitated discharge services, rehabilitation outreach teams) and research case registers. Participants will receive a complex multidisciplinary intervention focused on their goals and interests for up to 12 weeks. The intervention will be delivered by occupational therapists, physiotherapists and rehabilitation support workers. Feasibility outcomes will include recruitment and retention, suitability and acceptability of outcome measures and acceptability, feasibility and fidelity of intervention components. PWD outcome measures will include number of falls, Montreal Cognitive Assessment (MOCA), European Quality of Life Instrument (EQ-5D-5L), Quality of Life-Alzheimer's Disease Scale (QOL-AD), Modified Falls Efficacy Scale (MFES) and Goal Attainment Scaling (GAS). PWD outcome measures completed by an informal carer will include Disability Assessment for Dementia (DAD), EQ-5D-5L Proxy, QoL-AD Proxy and a Health Utilisation Questionnaire (HUQ). The carer outcome measure will be the Zarit Burden Interview (ZBI). An embedded process evaluation will explore barriers and facilitators to recruitment and intervention delivery. DISCUSSION: the study results will inform whether and how a larger multicentre RCT should be undertaken. A full RCT would have the potential to show how outcomes can be improved for people with dementia who have fallen. ETHICS AND DISSEMINATION: the National Research Ethics Service Committee Newcastle and North Tyneside 2 approved the feasibility study. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Registry. Registration number: ISRCTN41760734. Date of registration: 16/11/2015.

Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.

PLAIN ENGLISH SUMMARY: Why did we do this study? it can be difficult for scientists to communicate their research findings to the public. This is partly due to the complexity of translating scientific language into words that the public understand. Further, it may be hard for the public to find out about and locate information about research studies. We aimed to adapt some scientific articles about the links between dementia and stroke into lay summaries to be displayed online for the general public. How did we do it? We collaborated with five people from a volunteer organisation, VOICENorth. They took part in two group discussions about studies reporting on the link between dementia and stroke, and selected four studies to translate into lay summaries and display on a website. We discussed the layout and language of the summaries and made adaptations to make them more understandable to the general public. What did we find? We were able to work with members of the public to translate research findings into lay summaries suitable for a general audience. We made changes to language and layout including the use of 'question and answer' style layouts, the addition of a reference list of scientific terms, and removing certain words. What does this mean? Working with members of the public is a realistic way to create resources that improve the accessibility of research findings to the wider public. ABSTRACT: Background Scientific research is often poorly understood by the general public and difficult for them to access. This presents a major barrier to disseminating and translating research findings. Stroke and dementia are both major public health issues, and research has shown lifestyle measures help to prevent them. This project aimed to select a series of studies from the Newcastle Cognitive Function after Stroke cohort (COGFAST) and create lay summaries comprehensible and accessible to the public. Methods We used a focus group format to collaborate with five members of the public to review COGFAST studies, prioritise those of most interest to the wider public, and modify the language and layout of the selected lay summaries. Focus groups were audio-taped and the team used the data to make iterative amendments, as suggested by members of the public, to the summaries and to a research website. We calculated the Flesch reading ease and Flesch-Kincaid grade level for each summary before and after the changes were made. Results in total, we worked with five members of the public in two focus groups to examine draft lay summaries, created by researchers, relating to eight COGFAST studies. Members of the public prioritised four COGFAST lay summaries according to the importance of the topic to the general public. We made a series of revisions to the summaries including the use of 'question and answer' style layouts, the addition of a glossary, and the exclusion of scientific jargon. Group discussion highlighted that lay summaries should be engaging, concise and comprehensible. We incorporated suggestions from members of the public into the design of a study website to display the summaries. The application of existing quantitative tools to estimate readability resulted in an apparently paradoxical increase in complexity of the lay summaries following the changes made. Conclusion This study supports previous literature demonstrating challenges in creating generic guidelines for researchers to create lay summaries. Existing quantitative metrics to assess readability may be inappropriate for assessing scientific lay summaries. We have shown it is feasible and successful to involve members of the public to create lay summaries to communicate the findings of complex scientific research. Trial registration Not applicable to the lay summary project.

INTRODUCTION: the Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). METHODS: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. RESULTS: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. DISCUSSION: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

BACKGROUND: Neuroimaging features associated with vascular cognitive impairment have not been examined in sub-Saharan Africans. We determined magnetic resonance imaging (MRI) features associated with cognitive impairment in a sample of Nigerian stroke survivors. METHODS: Stroke survivors underwent brain MRI with standardized assessment of brain volumes and visual rating of medial temporal lobe atrophy (MTA), and white matter hyperintensities (WMH) at 3 months post-stroke. Demographic, clinical and psychometric assessments of global cognitive function, executive function, mental speed and memory were related to changes in structural MRI. RESULTS: in our pilot sample of 58 stroke survivors (60.1 ± 10.7 years old) MTA correlated significantly with age (r = 0.525), WMH (r = 0.461), memory (r = -0.702), executive function (r = -0.369) and general cognitive performance (r = -0.378). On univariate analysis, age >60 years (p = 0.016), low educational attainment (p < 0.001 to p < 0.003), total brain volume (p < 0.024 and p < 0.025) and MTA (p < 0.003 to p < 0.007) but not total WMH (p < 0.073, p = 0.610) were associated with cognitive outcome. In a two-step multivariate regression analysis, MTA (p < 0.035 and p < 0.016) and low educational attainment (p < 0.012 and p < 0.019) were sustained as independent statistical predictors of cognitive outcome. CONCLUSIONS: Medial temporal lobe atrophy was a significant neuroimaging predictor of early post-stroke cognitive dysfunction in the Nigerian African stroke survivors. These observations have implications for a vascular basis of MTA in older stroke survivors among sub-Saharan Africans.

Stroke is a major risk factor for the development of dementia in the elderly. It is unclear which genes influence risk of delayed dementia after stroke. We tested a single nucleotide polymorphism (SNP) in endothelial nitric oxide synthase (NOS3) gene at codon 298 (single-nucleotide polymorphism rs1799983; p.Asp298Glu) in a cohort of 355 older (>75 years) stroke survivors, who had detailed cognitive assessments from 3 months poststroke, i.e. baseline when the patients were free of dementia and subsequently at annual intervals. of these, 253 participants were genotyped for polymorphisms in NOS3 and apolipoprotein E (APOE). Our analysis showed that homozygosity for NOS3 TT rather than the GT or GG genotype was a significant factor in the development of dementia. The presence of TT genotype increased risk of incident dementia compared with GG genotype; hazard ratio, 3.14 (95% confidence interval, 1.64-5.99; p = 0.001). We hypothesize that this may be mediated by reduction of nitric oxide production and cerebral perfusion. Our findings, if replicated widely, have implications for treatments to ameliorate cognitive decline in stroke survivors. © 2011 Elsevier Inc.

Background: Falls are a major cause of morbidity and mortality in dementia, but there have been no prospective studies of risk factors for falling specific to this patient population, and no successful falls intervention/prevention trials. This prospective study aimed to identify modifiable risk factors for falling in older people with mild to moderate dementia. Methods and Findings: 179 participants aged over 65 years were recruited from outpatient clinics in the UK (38 Alzheimer's disease (AD), 32 Vascular dementia (VAD), 30 Dementia with Lewy bodies (DLB), 40 Parkinson's disease with dementia (PDD), 39 healthy controls). A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospectively for 12 months. Dementia participants experienced nearly 8 times more incident falls (9118/1000 person-years) than controls (1023/1000 person-years; incidence density ratio: 7.58, 3.11-18.5). In dementia, significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder (proportional hazard ratio (HR) adjusted for age and sex: 3.33, 2.11-5.26), and history of falls in the preceding 12 months (HR: 2.52, 1.52-4.17). In multivariate analyses, significant potentially modifiable predictors were symptomatic orthostatic hypotension (HR: 2.13, 1.19-3.80), autonomic symptom score (HR per point 0-36: 1.055, 1.012-1.099), and Cornell depression score (HR per point 0-40: 1.053, 1.01-1.099). Higher levels of physical activity were protective (HR per point 0-9: 0.827, 0.716-0.956). Conclusions: the management of symptomatic orthostatic hypotension, autonomic symptoms and depression, and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia. Randomised controlled trials to assess such a strategy are a priority. © 2009 Allan et al.

BACKGROUND: There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). AIMS: to assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification. RESULTS: There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p

Background/Aims: There is little published data regarding autonomic symptoms in dementia. This study aimed to examine the prevalence and severity of autonomic symptoms in patients with different subtypes of dementia in comparison with healthy controls, and their association with levels of physical activity, depression, quality of life and ability to carry out activities of daily living. Methods: Prevalence and severity of autonomic symptoms in Parkinson's disease dementia (PDD, n = 46), dementia with Lewy bodies (DLB, n = 32), vascular dementia (VAD, n = 38), Alzheimer's disease (AD, n = 40) and healthy controls (n = 42) were assessed using a structured symptom scale. The associations between autonomic symptoms and physical activity, Bristol Activities of Daily Living Score, Geriatric and Cornell Depression Scores and quality of life (Medical Outcomes Study 36-Item Short Form Health Survey, SF-36) were examined by multiple linear regressions. Results: Total autonomic symptom scores, urinary symptoms, constipation and postural dizziness were significantly higher in PDD, DLB and VAD patients than either controls or AD patients (all p < 0.05). Higher autonomic symptom scores were associated with poorer outcomes in all measures of physical activity, activities of daily living, depression and quality of life. Conclusion: the burden of autonomic symptoms is high in non-Alzheimer's dementias. The identification of such symptoms is of importance because of the detrimental effect of these symptoms upon physical activity, depression, activities of daily living and quality of life. Copyright © 2006 S. Karger AG.

Heart rate variability (HRV) is a sensitive method for the assessment of autonomic function and requires little cooperation from the subject, making it suitable for use in dementia. Preliminary studies have suggested that HRV may be impaired in Alzheimer's disease (AD). HRV has not been studied in vascular dementia (VAD). We investigate autonomic function in AD and VAD, using power spectral analysis of HRV. One hundred and fourteen participants were evaluated (14 AD, 20 VAD and 80 controls). The resting ECG was recorded for 5 min with participants in the supine position. Power spectral analysis used to obtain spectral bands in the very-low-frequency (

BACKGROUND AND PURPOSE: Impaired autonomic function is common in the acute poststroke phase but little is known about the longer term effects, particularly in older people. We sought to determine if autonomic function is impaired after stroke recovery in older patients. METHODS: a cross-sectional case-control study comparing autonomic function in 76 nondemented stroke patients with 70 community-living controls aged older than 75 years. RESULTS: Cases were assessed on average 9 months after stroke. From power spectral analysis of heart rate variability, stroke patients had lower total (P=0.032) and low-frequency (P=0.014) spectral densities and impaired baroreflex sensitivity (alpha low-frequency baroreflex sensitivity, P=0.006). From a series of cardiovascular autonomic reflex tests, heart rate variation during forced respiration, Valsalva ratio, and blood pressure overshoot during Valsalva maneuver were significantly lower in stroke patients (P=0.003,

OBJECTIVES: to compare the prevalence, severity, and type of gait and balance disorders in Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), Parkinson's disease without dementia (PD), and age-matched controls. DESIGN: Cross-sectional. SETTING: Secondary care clinics in geriatric psychiatry, neurology, and geriatrics. PARTICIPANTS: Two hundred forty-five participants aged 65 and older (AD, n = 40; VaD, n = 39; PDD, n = 46; DLB, n = 32; PD, n = 46; and controls, n = 42). MEASUREMENTS: Prevalence and severity of gait and balance disorders were assessed using the Tinetti gait and balance scale. The types of gait disorders in each diagnostic group were classified using the Nutt et al. classification. RESULTS: Gait and balance disorders were more common with PDD (93%), VaD (79%), and DLB (75%) than with PD (43%) and AD (25%) and in controls (7%). The risk of gait and balance disorder was higher in the non-Alzheimer's dementia groups (VaD, PDD, and DLB) than in the AD group (odds ratio = 15 (95% confidence interval = 6-37). If a gait disorder was present in mild dementia (Cambridge Examination for Mental Disorders of the Elderly cognitive subsection score >65), this was diagnostic of non-Alzheimer's dementia, with sensitivity of 78% and specificity of 100%. Non-Alzheimer's dementia groups had worse Tinetti gait and balance scores than the AD group (all P <. 001). The types of gait disorders discriminated between non-Alzheimer's dementias. CONCLUSION: the findings support the idea that gait and balance assessment may augment the diagnostic evaluation of dementia. © 2005 by the American Geriatrics Society.

Background. Post-stroke cognitive impairment is frequent, with characteristic impairments of attentional and executive performance. Objective. The study aims to determine whether the profile and severity of impairment in vascular Cognitive Impairment No Dementia (vascular CIND) is intermediate between that seen in stroke patients without significant cognitive impairment and patients with post-stroke dementia and thus to establish if the potential value of vascular CIND is a useful concept for predicting further cognitive decline and dementia in stroke patients. Methods. Stroke patients (n = 381) >75 were recruited from representative hospital-based stroke registers in Tyneside and Wearside, UK. Sixty six age matched controls were also recruited. A detailed battery of neuropsychological assessments was completed 3 months post stroke. Results. Deficits of attention (z = 5.7; p < 0.0001) and executive function (z = 5.9; p < 0.0001) were seen even in stroke patients without vascular CIND, compared to controls. However, stroke patients with CIND were significantly more impaired again on tests of executive function (z = 10.3; p < 0.0001) compared to those not meeting CIND criteria; and also had greater impairments of memory (z = 10.4; p < 0.0001) and language expression (z = 10.1; p < 0.0001). A similar overall profile of deficits was evident in the CIND and the dementia group, but specific deficits were significantly more pronounced in those with dementia, particularly in orientation (z = 7.2; p < 0.0001) and memory (z = 5.8; p < 0.0001). Conclusions. The current study indicates that attentional and executive impairments are frequent in stroke patients, but deficits of memory, orientation and language are more indicative of CIND and dementia. Further longitudinal studies are required to clarify the relationship between specific lesions and the progression of specific cognitive deficits in post-stroke patients. Copyright © 2004 John Wiley & Sons, Ltd.