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We will use UK Biobank data to assess whether ethnicity modifies the impact of dementia risk factors on dementia risk.

Supporting communication is important for reducing the impact of communication difficulties of people with dementia on overall well-being. There are evidence-based strategies that carers can use to support people with dementia. Paid and family carers may access advice from charities and health sites via the internet rather than journals. We aim to find what advice is given, and compare this to the evidence-base.

Supplemental Material, sj-pdf-1-dem-10.1177_14713012221076954 for Experience of UK Latin Americans caring for a relative living with dementia: A qualitative study of family carers by Stefanny Guerra, Tiffeny James, Penny Rapaport and Gill Livingston in Dementia.

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Background The objectives of this study were to describe changes in the proportion of people diagnosed with dementia and the pharmacological treatments prescribed to them over a 10 year period from 2005 to 2015 at a time of UK policy strategies and prioritisation of dementia. We aimed to explore the potential impact of policy on dementia care. Methods In this longitudinal retrospective cohort study, we included all patients registered at a Clinical Practice Research Datalink (CPRD) practice between July 1, 2005, and June 30, 2015, with a diagnosis of dementia defined using Read codes. The main outcomes were the number and proportion of acceptable patients, who met the CPRD threshold for data quality, in a GP practice defined by the CPRD as contributing up-to-standard data with a diagnosis of dementia and the number and proportion of these with a prescription for an antidementia or antipsychotic medication. We examined the prevalence of dementia diagnosis and prescribing by calendar quarter, and stratified by age, sex, and UK country (England, Scotland, Wales, or Northern Ireland). We investigated the use of antidementia drugs, alone and in combination, antipsychotics, antidepressants, anxiolytics, and hypnotics. The trend in the proportion of patients with a diagnosis of dementia, before and after the introduction of the UK National Dementia Strategy, was estimated using an interrupted time-series analysis. Findings 8 966 224 patients were identified in the CPRD whose most recent registration period overlapped the study period. Of these, 128 249 (1·4%) had a diagnosis of dementia before the end of the study period. The proportion of people diagnosed with dementia in the UK doubled from 0·42% (19 635 of 4 640 290 participants) in 2005 to 0·82% (25 925 of 3 159 754 participants) in 2015 (χ2 test for trend, p

Table S1. Full list of search terms. Table S2. Full data extracted from included studies and full references. Table S3. Quality rating criteria and scores for included studies. Table S4. Risk of hospitalisation in people with dementia compared to people without dementia: full details of GRADE rating of evidence strength. Table S5. Percentage of study participants hospitalised in the study period. Table S6. Association of potential risk factors with hospitalisation in people with dementia: full details of GRADE rating of evidence strength for risk factors. (DOCX 147 kb)

ObjectiveTo test the hypothesis that leisure activity participation is associated with lower dementia risk, we examined the association between participation in leisure activities and incident dementia in a large longitudinal study with average 18-year follow-up.MethodsWe used data from 8,280 participants of the Whitehall II prospective cohort study. A 13-item scale assessed leisure activity participation in 1997–1999, 2002–2004, and 2007–2009, and incidence of dementia (n cases = 360, mean age at diagnosis 76.2 years, incidence rate 2.4 per 1,000 person-years) was ascertained from 3 comprehensive national registers with follow-up until March 2017. Primary analyses were based on complete cases (n = 6,050, n cases = 247) and sensitivity analyses used multiple imputation for missing data.ResultsParticipation in leisure activities at mean age 55.8 (1997–1999 assessment), with 18.0-year follow-up, was not associated with dementia (hazard ratio [HR] 0.92 [95% confidence interval 0.79–1.06]), but those with higher participation at mean age 65.7 (2007–2009 assessment) were less likely to develop dementia with 8.3-year follow-up (HR 0.82 [0.69–0.98]). No specific type of leisure activity was consistently associated with dementia risk. Decline in participation between 1997–1999 and 2007–2009 was associated with subsequent dementia risk.ConclusionOur findings suggest that participation in leisure activities declines in the preclinical phase of dementia; there was no robust evidence for a protective association between leisure activity participation and dementia. Future research should investigate the sociobehavioral, cognitive, and neurobiological drivers of decline in leisure activity participation to determine potential approaches to improving social participation of those developing dementia.

OBJECTIVE: National and global dementia plans have focused on the research ambition to develop a cure or disease-modifying therapy by 2025, with the initial focus on investment in drug discovery approaches. We set out to develop complementary research ambitions in the areas of prevention, diagnosis, intervention, and care and strategies for achieving them. METHODS: Alzheimer's Society facilitated a taskforce of leading UK clinicians and researchers in dementia, UK funders of dementia research, people with dementia, and carer representatives to develop, using iterative consensus methodology, goals and recommendations to advance dementia research. RESULTS: The taskforce developed 5 goals and 30 recommendations. The goals focused on preventing future cases of dementia through risk reduction, maximising the benefit of a dementia diagnosis, improving quality of life, enabling the dementia workforce to improve practice, and optimising the quality and inclusivity of health and social care systems. Recommendations addressed gaps in knowledge and limitations in research methodology or infrastructure that would facilitate research in prioritised areas. A 10-point action plan provides strategies for delivering the proposed research agenda. CONCLUSIONS: By creating complementary goals for research that mirror the need to find effective treatments, we provide a framework that enables a focus for new investment and initiatives. This will support a broader and more holistic approach to research on dementia, addressing prevention, surveillance of population changes in risk and expression of dementia, the diagnostic process, diagnosis itself, interventions, social support, and care for people with dementia and their families.

Appendix 1. Association between clinical and demographic characteristics and the mini-mental state examination at death, using only scores recorded within one year of death. Appendix 2. Flow diagram of study patient inclusion/exclusion. (DOCX 41 kb)

Supplemental Material for An intervention to improve sleep for people living with dementia: Reflections on the development and co-production of DREAMS:START (Dementia RElAted Manual for Sleep: STrAtegies for RelaTives) by Penny Rapaport, Lucy Webster, Rossana Horsley, Simon D Kyle, Kirsi M Kinnunen, Brendan Hallam, James Pickett and Claudia Cooper in Dementia

SummarySeveral proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer’s disease (AD), Huntingtin (HTT) for Huntington’s disease, Parkin (PARK2) for Parkinson’s disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.

The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample. The disease prediction accuracy was investigated in a subset of the IGAP data, a sample of 3049 cases and 1554 controls (for whom APOE genotype data were available) by means of sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and positive and negative predictive values. We observed significant evidence for a polygenic component enriched in Alzheimer's disease (P = 4.9 × 10(-26)). This enrichment remained significant after APOE and other genome-wide associated regions were excluded (P = 3.4 × 10(-19)). The best prediction accuracy AUC = 78.2% (95% confidence interval 77-80%) was achieved by a logistic regression model with APOE, the polygenic score, sex and age as predictors. In conclusion, Alzheimer's disease has a significant polygenic component, which has predictive utility for Alzheimer's disease risk and could be a valuable research tool complementing experimental designs, including preventative clinical trials, stem cell selection and high/low risk clinical studies. In modelling a range of sample disease prevalences, we found that polygenic scores almost doubles case prediction from chance with increased prediction at polygenic extremes.

GRB-associated binding protein 2 (GAB2) represents a compelling genome-wide association signal for late-onset Alzheimer's disease (LOAD) with reported odds ratios (ORs) ranging from 0.75-0.85. We tested eight GAB2 variants in four North American Caucasian case-control series (2,316 LOAD, 2,538 controls) for association with LOAD. Meta-analyses revealed ORs ranging from (0.61-1.20) with no significant association (all p>0.32). Four variants were hetergeneous across the populations (all p

Study protocol. (PDF 100 kb)

Study protocol. (PDF 100 kb)