Search

Aim: A growing evidence‐base indicates that dementia occurrence can be changed. This has been linked to potentially modifiable risk factors. Risk reduction and primary prevention strategies are increasingly recognized as needing to include population‐level policies to tackle the social and commercial determinants of health. How this knowledge can influence policymaking on dementia prevention is unknown. Understanding attitudes of policymakers is an important step in translating evidence into practice, helping to gauge system readiness for implementation, and potential barriers and enablers for influencing policy. The aim of this qualitative study is to explore the understanding of, and attitudes to, dementia risk reduction and population‐level prevention strategies amongst English policymakers at national, regional, and local level. Methods: Semi‐structured interviews were undertaken with a range of dementia and prevention policymakers, with purposive sampling of national and local policymakers, including politicians, government officials, health system leaders, academics, and dementia charity directors. Analysis of interview transcripts was undertaken by thematic analysis. Results: 14 policymakers were interviewed between November 2021 and February 2022. Three main themes were identified (1) Preventability of dementia, (2) Prevention approach, (3) Barriers and facilitators to improving the approach. Discussion: Policymakers generally held dementia to be partially preventable. Policymakers recognised that both individual‐ and population‐level approaches to primary prevention of dementia are required – with some policymakers perceiving that population‐level approaches are under‐utilised. Key barriers to implementing more population‐level approaches were identified as the complexity and co‐ordination required to effectively tackle upstream determinants of health. Key points: Adoption of policies to address the upstream, social and commercial determinants of brain health are required to significantly reduce the prevalence of dementia and reduce inequalities, but these policies can only be implemented by coordinated action between various policymakers.We interviewed 14 policymakers related to national and local prevention policy and dementia policy.Policymakers generally held dementia to be preventable, and suggested the need for both individual‐level and population‐level interventions.Further work is needed to equip policymakers with the knowledge, resources, and structures required to successfully implement more population‐level dementia risk reduction policies. [ABSTRACT FROM AUTHOR]

South‐Eastern Europe only recently was required to adapt their domestic law to adhere to European Union legislations and standards. As such, it forms an excellent case study on how and to what extent the 'Europeanisation' process is interacting with the development of special education needs (SEN) policy, particularly focusing on autistic children. This scoping review mapped autism and special education policies of Bulgaria, Romania, and Croatia and investigated how Europeanisation interacted with autism and educational policy through a path dependence analysis. Our research shows that education for children with special needs started with segregation during communist time. EU accession since then has influenced disability policies and contributed to establishing inclusive education for all students. One particular Romanian policy resulted in children with special needs not having to compete with typical children for school submission. Ultimately, the majority of policies addressed special education needs in general. Only Romania adopted specific autism policy. Inclusive education is being developed in all countries. [ABSTRACT FROM AUTHOR]

To identify factors that predict the risk of loneliness for people with dementia and carers during a pandemic. People with dementia and their carers completed assessments before (July 2019–March 2020; 206 dyads) and after (July–October 2020) the first Covid-19 'lockdown' in England. At follow-up, the analytic sample comprised 67 people with dementia and 108 carers. We built a longitudinal path model with loneliness as an observed outcome. Carer type and social contacts at both measurements were considered. Other social resources (quality of relationship, formal day activities), wellbeing (anxiety, psychological wellbeing) and cognitive impairment were measured with initial level and change using latent growth curves. We adjusted for socio-demographic factors and health at baseline. In carers, higher levels of loneliness were directly associated with non-spouse coresident carer type, level and increase of anxiety in carer, more formal day activities, and higher cognitive impairment in the person with dementia. In people with dementia, non-spouse coresident carer type, and higher initial levels of social resources, wellbeing, and cognitive impairment predicted the changes in these factors; this produced indirect effects on social contacts and loneliness. Loneliness in the Covid-19 pandemic appears to be shaped by different mechanisms for people with dementia and their carers. The results suggest that carers of those with dementia may prioritize providing care that protects the person with dementia from loneliness at the cost of experiencing loneliness themselves. Directions for the promotion of adaptive social care during the Covid-19 pandemic and beyond are discussed. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic and associated social distancing measures have profoundly impacted society and social contact patterns, with older people disproportionately affected. Concerns have been raised about a resulting pandemic of loneliness in older people, although the current evidence is mixed. This study provides a unique perspective on the prevalence of loneliness in a population cohort of older people before the pandemic, followed up after the introduction of social restrictions. Methods: Data analysis was conducted using Wave 3 of the longitudinal Cognitive Function and Aging Study II (2018–2019) and a sub‐study focusing on experiences during the COVID‐19 pandemic (2020). The sample comprised 379 adults aged over 75 living in Cambridge, Newcastle, and Nottingham. Multivariable binary logistic regression was conducted to identify correlates of prevalent loneliness, adjusted for confounding covariates, during the pandemic. The prevalence of loneliness during the pandemic was compared to loneliness in 2018–2019. Results: Prevalence of loneliness in this sample during the pandemic was 25.1% (95% CI 20.9%–29.7%) compared to 17.2% (95% CI 13.7%–21.3%) in 2018–2019 (χ2 = 14.1, p < 0.01). Variables associated with increased odds of prevalent loneliness included: prior loneliness, living alone, female gender, living in an area of higher deprivation, frequent pre‐pandemic social contact at community groups, and separation from family during the pandemic, adjusted for age and sex. Weekly technology‐mediated contact using telephone or video calls was associated with lower odds of loneliness. Conclusions: COVID‐19 recovery plans should address loneliness in older people. Target groups should include those who have previously been lonely, people who live alone, those living in deprived areas, and those who had previously been socially active through community groups. [ABSTRACT FROM AUTHOR]

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there is a lack of large studies with objective measures of vision and with more than 10 years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). In both cohorts, visual acuity was measured using a "logarithm of the minimum angle of resolution" (LogMAR) chart and categorized as no (≤0.30 LogMAR), mild (>0.3 to ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62 206 UK Biobank and 7 337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk, respectively, 1 113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable Cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% confidence interval [CI]: 0.92-1.72) and 2.16 (95% CI: 1.37-3.40), in UK Biobank, and 1.05 (95% CI: 0.72-1.53) and 1.93 (95% CI: 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but was not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention; however, the possibility of reverse causation cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Despite increasing life expectancy (LE), cross-sectional data show widening inequalities in disability-free LE (DFLE) by socioeconomic status (SES) in many countries. We use longitudinal data to better understand trends in DFLE and years independent (IndLE) by SES, and how underlying transitions contribute.Methods: The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those aged ≥65 years in three English centres (Newcastle, Nottingham, Cambridgeshire), with baseline around 1991 (CFAS I, n = 7635) and 2011 (CFAS II, n = 7762) and 2-year follow-up. We defined disability as difficulty in activities of daily living (ADL), dependency by combining ADLs and cognition reflecting care required, and SES by area-level deprivation. Transitions between disability or dependency states and death were estimated from multistate models.Results: Between 1991 and 2011, gains in DFLE at age 65 were greatest for the most advantaged men and women [men: 4.7 years, 95% confidence interval (95% CI) 3.3-6.2; women: 2.8 years, 95% CI 1.3-4.3]. Gains were due to the most advantaged women having a reduced risk of incident disability [relative risk ratio (RRR):0.7, 95% CI 0.5-0.8], whereas the most advantaged men had a greater likelihood of recovery (RRR: 1.8, 95% CI 1.0-3.2) and reduced disability-free mortality risk (RRR: 0.4, 95% CI 0.3-0.6]. Risk of death from disability decreased for least advantaged men (RRR: 0.7, 95% CI 0.6-0.9); least advantaged women showed little improvement in transitions. IndLE patterns across time were similar.Conclusions: Prevention should target the most disadvantaged areas, to narrow inequalities, with clear indication from the most advantaged that reduction in poor transitions is achievable. [ABSTRACT FROM AUTHOR]

In the past decade a large body of evidence has accumulated on risk factors for dementia, primarily from Europe and North America. Drawing on recent integrative reviews and a consensus workshop, the International Research Network on Dementia Prevention developed a consensus statement on priorities for future research. Significant gaps in geographical location, representativeness, diversity, duration, mechanisms, and research on combinations of risk factors were identified. Future research to inform dementia risk reduction should fill gaps in the evidence base, take a life-course, multi-domain approach, and inform population health approaches that improve the brain-health of whole communities. [ABSTRACT FROM AUTHOR]

Background: The current evidence for higher physical activity and better cognitive function and lower risk of dementia is strong but not conclusive. More robust evidence is needed to inform public-health policy. We provide further insight into discrepancies observed across studies, reporting on habitual inactivity including that during work.Methods: We examined cross-sectional and prospective relationships of physical inactivity during leisure and occupation time, with cognitive performance using a validated physical-activity index in a cohort of 8585 men and women aged 40-79 years at baseline (1993-1997) for different domains using a range of cognitive measures. Cognitive testing was conducted between 2006 and 2011 (including a pilot phase 2004-2006). Associations were examined using multinomial logistic-regression adjusting for socio-demographic and health variables as well total habitual physical activity.Results: Inactivity during work was inversely associated with poor cognitive performance (bottom 10th percentile of a composite cognition score): odds ratio (OR) = 0.68 [95% confidence interval (CI) 0.54, 0.86], P = 0.001. Results were similar cross-sectionally: OR = 0.65 (95% CI 0.45, 0.93), P = 0.02. Manual workers had increased risk of poor performance compared with those with an occupation classified as inactive. Inactivity during leisure time was associated with increased risk of poor performance in the cross-sectional analyses only.Conclusions: The relationship between inactivity and cognition is strongly confounded by education, social class and occupation. Physical activity during leisure may be protective for cognition, but work-related physical activity is not protective. A greater understanding of the mechanisms and confounding underlying these paradoxical findings is needed. [ABSTRACT FROM AUTHOR]

Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.Objective: To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.Methods: We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.Results: Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer's disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18-0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11-19.24) and 3.30 (1.02-10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.Conclusions: We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer's disease; however, we cannot rule out effects owing to small numbers. [ABSTRACT FROM AUTHOR]

Objectives: DETERMIND (DETERMinants of quality of life, care and costs, and consequences of INequalities in people with Dementia and their carers) is designed to address fundamental, and, as yet unanswered questions about inequalities, outcomes and costs following diagnosis with dementia. These answers are needed to improve the quality of care and equity of access to care, and therefore the quality of life, of people with dementia and their carers.Method: DETERMIND is a programme of research consisting of seven complementary workstreams (WS) exploring various components that may result in unequal dementia care: WS1: Recruitment and follow-up of the DETERMIND cohort-900 people with dementia and their carers from three geographically and socially diverse sites within six months following diagnosis, and follow them up for three years. WS2: Investigation of the extent of inequalities in access to dementia care. WS3: Relationship between use and costs of services and outcomes. WS4: Experiences of self-funders of care. WS5: Decision-making processes for people with dementia and carers. WS6: Effect of diagnostic stage and services on outcomes. WS7: Theory of Change informed strategy and actions for applying the research findings.Outcomes: During the life of the programme, analysing baseline results and then follow-up of the DETERMIND cohort over 3 years, we will establish evidence on current services and practice. DETERMIND will deliver novel, detailed data on inequalities in dementia care and what drives positive and negative outcomes and costs for people with dementia and carers, and identify factors that help or hinder living well with dementia. [ABSTRACT FROM AUTHOR]

Background: Delirium is common, affecting at least 20% of older hospital inpatients. It is widely accepted that delirium is associated with dementia but the degree of causation within this relationship is unclear. Previous studies have been limited by incomplete ascertainment of baseline cognition or a lack of prospective delirium assessments. There is an urgent need for an improved understanding of the relationship between delirium and dementia given that delirium prevention may plausibly impact upon dementia prevention. A well-designed, observational study could also answer fundamental questions of major importance to patients and their families regarding outcomes after delirium. The Delirium and Cognitive Impact in Dementia (DECIDE) study aims to explore the association between delirium and cognitive function over time in older participants. In an existing population based cohort aged 65 years and older, the effect on cognition of an episode of delirium will be measured, independent of baseline cognition and illness severity. The predictive value of clinical parameters including delirium severity, baseline cognition and delirium subtype on cognitive outcomes following an episode of delirium will also be explored.Methods: Over a 12 month period, surviving participants from the Cognitive Function and Ageing Study II-Newcastle will be screened for delirium on admission to hospital. At the point of presentation, baseline characteristics along with a number of disease relevant clinical parameters will be recorded. The progression/resolution of delirium will be monitored. In those with and without delirium, cognitive decline and dementia will be assessed at one year follow-up. We will evaluate the effect of delirium on cognitive function over time along with the predictive value of clinical parameters.Discussion: This study will be the first to prospectively elucidate the size of the effect of delirium upon cognitive decline and incident dementia. The results will be used to inform future dementia prevention trials that focus on delirium intervention. [ABSTRACT FROM AUTHOR]

Background: Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people.Methods and Findings: We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve.Conclusions: Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life. [ABSTRACT FROM AUTHOR]

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated.Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia.Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors.Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed.Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death.Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls.Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia. [ABSTRACT FROM AUTHOR]

Background: Moderate obesity in later life may improve survival, prompting calls to revise obesity control policies. However, this obesity paradox may be due to confounding from smoking, diseases causing weight-loss, plus varying follow-up periods. We aimed to estimate body mass index (BMI) associations with mortality, incident type 2 diabetes, and coronary heart disease in older people with and without the above confounders.Methods: Cohort analysis in Clinical Practice Research Datalink primary care, hospital and death certificate electronic medical records in England for ages 60 to more than 85 years. Models were adjusted for age, gender, alcohol use, smoking, calendar year, and socioeconomic status.Results: Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall death rates in all age groups. However, after excluding the specific confounders and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U-shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply rising risks above. In older age groups, mortality nadirs were at modestly higher BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity-1 at all ages and for coronary heart disease to age 84.Conclusions: Obesity is associated with shorter survival plus higher incidence of coronary heart disease and type 2 diabetes in older populations after accounting for the studied confounders, at least to age 84. These results cast doubt on calls to revise obesity control policies based on the claimed risk paradox at older ages. [ABSTRACT FROM AUTHOR]

Background: More information about the pattern of behavioural and psychological symptoms of dementia (BPSD) in the course of dementia is needed to inform patients and clinicians and to design future interventions.Aims: To determine the persistence and incidence of BPSD and their relation to cognitive function, in individuals with dementia or in cohorts investigated for dementia onset.Method: A systematic literature review analysed the baseline prevalence, persistence and incidence of 11 symptoms. The review was conducted according to established guidelines with the exception that we could not exclude the possibilities of bias in the studies examined.Results: The 59 included studies showed considerable heterogeneity in their objectives and methods. The symptoms hyperactivity and apathy showed high persistence and incidence; depression and anxiety low or moderate persistence and moderate incidence; and psychotic symptoms low persistence with moderate or low incidence.Conclusions: Despite heterogeneity across studies in terms of setting, focus and length of follow-up, there were clinically relevant differences in the longitudinal courses of different BPSD. Apathy was the only symptom with high baseline prevalence, persistence and incidence during the course of dementia. [ABSTRACT FROM AUTHOR]

Background: Genetic risk factors for Alzheimer's disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes.Methods: Using the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer's pathology. Cerebral cortex obtained at post-mortem from 299 participants was analysed by immunohistochemistry for cluster of differentiation (CD)68 (phagocytosis), human leukocyte antigen (HLA)-DR (antigen-presenting function), ionized calcium-binding adaptor molecule (Iba1) (microglial motility), macrophage scavenger receptor (MSR)-A (plaque-related phagocytosis) and CD64 (immunoglobulin Fcγ receptor I).Results: The presence of dementia was associated positively with CD68 (P < 0.001), MSR-A (P = 0.010) and CD64 (P = 0.007) and negatively with Iba1 (P < 0.001). Among participants without dementia, the cognitive function according to the Mini-Mental State Examination was associated positively with Iba1 (P < 0.001) and negatively with CD68 (P = 0.033), and in participants with dementia and Alzheimer's pathology, positively with all microglial markers except Iba1. Overall, in participants without dementia, the relationship with Alzheimer's pathology was negative or not significant, and positive in participants with dementia and Alzheimer's pathology. Apolipoprotein E (APOE) ε2 allele was associated with expression of Iba1 (P = 0.001) and MSR-A (P < 0.001) and APOE ε4 with CD68, HLA-DR and CD64 (P < 0.001).Conclusions: Our findings raise the possibility that in dementia with Alzheimer's pathology, microglia lose motility (Iba-1) necessary to support neurons. Conversely, other microglial proteins (CD68, MSR-A), the role of which is clearance of damaged cellular material, are positively associated with Alzheimer's pathology and impaired cognitive function. In addition, our data imply that microglia may respond differently to Aβ and tau in participants with and without dementia so that the microglial activity could potentially influence the likelihood of developing dementia, as supported by genetic studies, highlighting the complexity and diversity of microglial responses. [ABSTRACT FROM AUTHOR]

Background: Considerable variability exists in international prevalence and incidence estimates of dementia. The accuracy of estimates of dementia in the oldest-old and the controversial question of whether dementia incidence and prevalence decline at very old age will be crucial for better understanding the dynamics between survival to extreme old age and the occurrence and risk for various types of dementia and comorbidities. International Centenarian Consortium - Dementia (ICC-Dementia) seeks to harmonise centenarian and near-centenarian studies internationally to describe the cognitive and functional profiles of exceptionally old individuals, and ascertain the trajectories of decline and thereby the age-standardised prevalence and incidence of dementia in this population. The primary goal of the ICC-Dementia is to establish a large and thorough heterogeneous sample that has the power to answer epidemiological questions that small, separate studies cannot. A secondary aim is to examine cohort-specific effects and differential survivorship into very old age. We hope to lay the foundation for further investigation into risk and protective factors for dementia and healthy exceptional brain ageing in centenarians across diverse ethnoracial and sociocultural groups.Methods: Studies focusing on individuals aged ≥95 years (approximately the oldest 1 percentile for men, oldest 5th percentile for women), with a minimum sample of 80 individuals, including assessment of cognition and functional status, are invited to participate. There are currently seventeen member or potential member studies from Asia, Europe, the Americas, and Oceania. Initial attempts at harmonising key variables are in progress.Discussion: General challenges facing large, international consortia like ICC-Dementia include timely and effective communication among member studies, ethical and practical issues relating to human subject studies and data sharing, and the challenges related to data harmonisation. A specific challenge for ICC-Dementia relates to the concept and definition of'abnormal' in this exceptional group of individuals who are rarely free of physical, sensory and/or cognitive impairments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: the James Lind Alliance (JLA) created an approach to elicit the views of those under-represented in research priority exercises. Building on this, the JLA Dementia Priority Setting Partnership was set up as an independent and evidence-based project to identify and prioritise unanswered questions ('uncertainties') about prevention, diagnosis, treatment and care relating to dementia. Methods: a survey was widely disseminated to stakeholders with an interest in the needs of the older population. Thematic analysis was used to identify themes from the large amount of questions collected from which research questions were developed using PICO framework (Population, Intervention, Comparator, Outcome). Each question was checked against an extensive evidence base of high-quality systematic reviews to verify whether they were true uncertainties. Findings: one thousand five hundred and sixty-three questionnaires were received, from people with dementia, carers/relatives, and health and care professionals; 85 uncertainties were identified from other sources. Questions were refined and formatted iteratively into 146 unique uncertainties. An interim prioritisation process involving diverse organisations identified the top 25 ranked questions. At a final face-to-face prioritisation workshop, 18 people representing the above constituencies arrived by consensus at the top 10 priority questions. The impact of patient and public involvement on the priorities is discussed. Interpretation: the long (146 questions) and top 10 lists of dementia research priorities provide a focus for researchers, funders and commissioners. They highlight a need for more research into care for people with dementia and carers, and a need for high-quality effectiveness trials in all aspects of dementia research. [ABSTRACT FROM AUTHOR]

Background: Involving service users in the systematic review process is seen as increasingly important. As systematic reviews often include studies from diverse settings and covering a time span of several decades, involving service users in consideration of applicability to specific populations or settings might make reviews more useful to practitioners and policymakers. Objectives: To test and contextualize the findings of a systematic review of qualitative studies looking at patient and carer experiences of diagnosis and treatment of dementia. Methods: Results from the systematic review were discussed in focus groups and semi‐structured interviews with patient, public and professional participants in the South East of England. Analysis was guided by coding frameworks developed from the results of the systematic review. Participants: We recruited 27 participants, including three people with dementia, 12 carers, six service providers and five older people without dementia. Results: Findings from the focus groups and interviews were consistent with those from the systematic review and suggest that our review findings were applicable to the local setting. We found some evidence that access to information and diagnostic services had improved but, as in the systematic review, post‐diagnosis support was still often experienced as inadequate. Conclusions: Focus groups and interviews with service users and their representatives can provide useful contextual information. However, such strategies can require considerable investment of the part of the researcher in terms of time and resources, and more work is needed to refine strategies and establish the benefits for patients and the organization of services. [ABSTRACT FROM AUTHOR]

Background: non-participation in epidemiological studies threatens the generalisability of findings. Objective: to investigate the change in non-participation between the Medical Research Council Cognitive Function and Ageing Study (CFAS) I and II. Design: a comparison of two epidemiological studies of older people using identical methods. Setting: three geographical areas of the United Kingdom. Subjects: older people aged 65 years and over. Methods: the two studies were conducted approximately two decades apart between 1989 and 1994 (CFAS I) and between 2008 and 2011 (CFAS II). Random samples were drawn from primary care lists. We compared demographic factors associated with non-participation. Results: non-participation in CFAS II was higher than in CFAS I (45.3 versus 18.3%). After adjustment for confounders, in both CFAS I and CFAS II, women were more likely to decline to take part (CFAS I: odds ratio (OR) 1.3 95% confidence interval (CI) 1.2 to 1.4; CFAS II: 1.1 95% CI 1.1 to 1.2). Deprivation was associated with non-participation in both studies (highest versus lowest Townsend deprivation quintile, CFAS I: OR 1.4 95% CI 1.2 to 1.6; CFAS II: 2.0 95% CI 1.8 to 2.2). Age was not associated with non-participation in either study (CFAS I, P = 0.21; CFAS II, P = 0.47). Conclusions: non-participation in epidemiological studies of older people has increased substantially in the past two decades and public willingness to take part in studies of this kind would appear to be declining. As communities become more diverse and older people have increasing commitments on their time, new ways to engage prospective participants are urgently needed. [ABSTRACT FROM AUTHOR]

Background Community environment might play an important role in supporting ageing in place. This paper aims to explore relocation at older age and its associations with individual and community level factors. Methods The postcodes of the 2424 people in the year-10 interview of the Cognitive Function and Ageing Study (CFAS) in England were mapped onto Enumeration Districts and linked to their corresponding Townsend deprivation score and the 2011 rural/urban categories. Multilevel logistic regression was conducted to examine the influence of the baseline individual (age, gender, education and social class) and community (rural/urban categories and area deprivation) level factors on relocation over 10 years. Results One-third of people moved residence after the age of 65 years and over. Older age, low education, low social class and living in rural areas at baseline were associated with higher probability of moving later in life. The likelihood of relocation in later life increased from least to most deprived areas (odds ratio: 2.0, 95% confidence interval: 1.4, 2.8). Conclusions Urban/rural contexts and area deprivation are associated with relocation at older age and indicate that community environment may be relevant to ageing in place. [ABSTRACT FROM AUTHOR]

Background: criteria for mild cognitive impairment (MCI) capture an intermediate cognitive state between normal ageing and dementia, associated with increased dementia risk. Whether criteria for MCI are applicable in the context of stroke and can be used to predict dementia in stroke cases is not known.Objectives: to determine the prevalence of MCI in individuals with stroke and identify predictors of 2-year incident dementia in stroke cases.Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. MCI prevalence in individuals with stroke was determined. Logistic regression, with receiver operating characteristic curve analysis, was used to identify variables associated with risk of dementia in stroke cases including MCI criteria, demographic, health and lifestyle variables.Findings: of 2,640 individuals seen at the first assessment, 199 reported stroke with no dementia. In individuals with stroke, criteria for MCI are not appropriate, with less than 1% of stroke cases being classified as having MCI. However, in individuals with stroke two components of the MCI definition, subjective memory complaint and cognitive function (memory and praxis scores) predicted 2-year incident dementia (area under the curve = 0.85, 95% CI: 0.77–0.94, n = 113).Conclusion: criteria for MCI do not appear to capture risk of dementia in the context of stroke in the population. In stroke cases, subjective and objective cognitive performance predicts dementia and these variables could possibly be incorporated into dementia risk models for stroke cases. Identifying individuals with stroke at greatest risk of dementia has important implications for treatment and intervention. [ABSTRACT FROM PUBLISHER]

Sex differences in social and communication behaviours related to autism spectrum conditions (ASC) have been investigated mainly in Western populations. Little research has been done in Chinese populations. This study explored sex differences related to ASC characteristics by examining differences in item responses and score distributions in relation to a screening instrument, the Childhood Autism Spectrum Test (CAST), used with Chinese children. A Mandarin Chinese version of the CAST (M-CAST) was distributed to 737 children aged 6-11 years in mainstream schools in Beijing. Questionnaires from 682 (93 %) children were available for analysis. The median score for boys was higher than for girls [boys, median = 8 (IQR 6, 11); girls, median = 7 (IQR 4, 9); p < 0.001]. There were differences in the proportions of boys and girls across all three score groups (≤11, 12-14, ≥15) with more boys being found in the higher score groups ( p = 0.035). This finding provides evidence that boys and girls have different social and communication development profiles, consistent with previous findings in Western cultures. These results suggest that sex differences related to ASC are consistent across cultures. [ABSTRACT FROM AUTHOR]

Limited studies have investigated the latent autistic traits in the mainland Chinese population for autism spectrum conditions (ASC). This study explored the psychometric properties of a Mandarin Chinese version of the CAST in a sample consisting of 737 children in mainstream schools and 50 autistic cases. A combination of categorical data factor analysis and item response theory suggested a good-fit model of a two-factor solution for 28 items on the Mandarin CAST including social and communication, and inflexible/stereotyped language and behaviours (Goodness-of-fit indices: RMSEA = 0.029, CFI = 0.957, TLI = 0.950, SRMR = 0.064). The correlation between the two factors was moderate (GFC = 0.425). This study provided evidence for the CAST as a multidimensional measure for ASC screening in a Chinese population and also showed that the symptom manifestation of ASC in Chinese children shares similarity with western populations. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a common disorder among older people. Accurate epidemiological information is essential to identify possible aetiological factors, plan health services and set priorities for medical research.Objective: to determine the incidence of idiopathic Parkinson's disease in a defined geographical area in the North-East of England.Methods: using a prospective, longitudinal design, we sought to identify every new case of Parkinson's disease arising in the Newcastle and Gateshead area in the North-East of England. The base population comprised 488 576 individuals and multiple sources of case ascertainment were employed. All the patients with newly diagnosed idiopathic Parkinson's disease or parkinsonism between 1 June 2009 and 31 May 2011 were invited to participate. Patients were examined by a specialist and followed longitudinally to permit diagnostic review.Results: we identified 257 potential cases, of whom 181 had suspected idiopathic Parkinson's disease. After a follow-up period of 18 months, 155 patients retained a clinical diagnosis of probable Parkinson's disease. The mean age at diagnosis was 72.4 ± 10 years. The crude incidence of PD in Newcastle and Gateshead was 15.9 per 100 000 persons per year (95% CI: 13.4–18.4). Age-standardised to the European population the incidence of Parkinson's disease was 12.0 per 100 000 (95% CI: 10.1–14.0). We found a higher crude incidence among men 17.7 per 100 000 (95% CI: 14.0–21.4) than women 14.0 per 100 000 (95% CI: 10.7–17.4).Conclusion: in this prospective longitudinal study, the incidence rate of Parkinson's disease in North-East England is similar to that of other modern European and American studies. [ABSTRACT FROM AUTHOR]

Background: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally.Methods: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years.Results: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation.Conclusions: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population. [ABSTRACT FROM AUTHOR]

The article presents a study that explores end-of-life transitions of older old people across the cognitive spectrum. The study used mortality records linked to 283 Cambridge City over-75s Cohort participants' cognitive assessments less than one year before dying aged 85 years or more. One finding suggests that 55% their usual address on death registration was not their place of death.

Background: the terminal decline hypothesis suggests an acceleration in the rate of loss of cognitive function before death. Evidence about the association of educational attainment and the onset of terminal decline is scarce.Objective: to investigate the association of education with the onset of terminal decline in global cognitive function measured by Mini Mental State Exam (MMSE) scores.Subjects: deceased participants of the Cambridge City over 75 Cohort Study who were interviewed at about 2, 7, 9, 13, 17 and 21 years after baseline.Methods: regular and Tobit random change point growth models were fitted to MMSE scores to identify the onset of terminal decline and assess the effect of education on this onset.Results: people who left school at an older age had a delayed onset of terminal decline. Thus better educated individuals experience a slightly shorter period of faster decline before death.Conclusion: an important finding emerging from our work is that education does appear to delay the onset of terminal decline, although only by a limited amount. [ABSTRACT FROM PUBLISHER]

Background: being able to identify individuals at high risk of dementia is important for diagnostics and intervention. Currently, there is no standard approach to assessing cognitive function in older aged individuals to best predict incident dementia.Objective: to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG).Design: longitudinal population representative sample aged 65+ years.Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed.Results: from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy.Conclusion: in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework. [ABSTRACT FROM AUTHOR]

We tested for differences in the prevalence of autism spectrum conditions (ASC) in school-aged children in three geographical regions in the Netherlands. Schools were asked to provide the number of children enrolled, the number having a clinical diagnosis of ASC and/or two control neurodevelopmental conditions. Prevalence was evaluated by negative binomial regression and adjustments were made for non-response and size of the schools. The prevalence estimates of ASC in Eindhoven was 229 per 10,000, significantly higher than in Haarlem (84 per 10,000) and Utrecht (57 per 10,000), whilst the prevalence for the control conditions were similar in all regions. Phase two is planned to validate school-reported cases using standardized diagnostic methods and to explore the possible causes for these differences. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03-0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=−0.14-0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30-2.16; P<.001) and possible (OR=1.56; 95% CI=1.36-1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality. [ABSTRACT FROM AUTHOR]

Background: physical functioning describes the underlying abilities that make activities necessary for independent living in the community possible.Objective: to test self-reported and objective measures of physical functioning in predicting subsequent disability in cooking, shopping and housework.Design: we used data from the first and second waves of the Survey of Health, Ageing and Retirement in Europe. The respondents were asked about physical functioning (climbing, pulling/pushing, stooping/crouching/kneeling, lifting/carrying and reaching/extending were comparable) and they had their grip strength and walking speed measured.Participants: men and women aged 65 years or over who reported no disability in cooking, shopping and housework at baseline were included in the analysis. There were 6,841 individuals for whom data on disability status at follow-up were available.Methods: Poisson regression was used to calculate relative risks for the associations between self-reported and objective measures of physical functioning with disability at 2 years, adjusting for age, gender, educational level, cognitive function and chronic conditions.Results: those with limitations in physical functioning at baseline more frequently reported subsequent disability. Walking ability was most strongly associated with disability; climbing, pulling/pushing, lifting/carrying and reaching/extending were comparable (picking was non-significant). Similar results were obtained with grip strength and walking speed.Conclusions: both self-reports and objective measures capture information on the functional ability of older people that can be used to predict disability onset. Objective measures offer little to the development of intervention strategies, whereas self-reports provide some insight into the demands of the environment, being more amenable to interventions. [ABSTRACT FROM PUBLISHER]

Background: diagnosis of mild cognitive impairment (MCI) typically excludes individuals with medical co-morbidity. Interest in MCI screening raises the questions of what are the best criteria to identify a representative sample and what factors are associated with MCI progression to dementia.Objectives: to compare the pattern of disease co-morbidity across different cognitive groups and to examine the role of health co-morbidity as a risk factor for dementia progression from MCI.Methods: individuals from the MRC Cognitive Function and Ageing Study were classified as having no cognitive impairment (NCI), MCI, other cognitive impairment no dementia (OCIND) or dementia. At 2 years dementia status was assessed.Findings: over 50% of individuals in each group reported one or more medical condition. The pattern of disease prevalence was similar in the NCI, MCI and OCIND groups. Anaemia was the only health factor associated with an increased risk of dementia progression from MCI.Conclusion: classification of MCI using medical exclusions would exclude the majority of the population from a MCI diagnosis. This has implications for treatment decisions and clinical trial recruitment. This could not only make recruitment more difficult but also limit the generalisability of trial results. Medical co-morbidity does not help to distinguish progressive from non-progressive MCI. [ABSTRACT FROM PUBLISHER]

Background: In the older population, multimorbidity is common and 'best practice' may invite the prescription of multiple medications. Objective: To examine the association between polypharmacy, defined as the concurrent use of five or more prescription or nonprescription medications, and mortality in 12423 participants aged ≥65 years representative of the older population of England and Wales. Methods: Data on self-reported medication use, disability and health conditions were collected at baseline in 1991-3. The cohort was followed for up to 18 years with full mortality notification. Cox proportional hazards regression adjusted for age, baseline institutionalization, smoking, disability and health conditions was used to investigate polypharmacy and mortality, stratified by sex. Various methods for modelling the time-varying effect of polypharmacy are presented. Results: A strong independent association between polypharmacy and mortality existed in the short-term (first 2 years) for both men and women. This association remained, although attenuated, in the medium-long term (2-18 years of follow- up) for women, but became non-significant in the longer term for men. Conclusions: It remains unclear whether polypharmacy is a marker for poor health or is an independent risk factor for mortality. However, polypharmacy strongly predicts adverse outcomes, and multiple medication use should therefore be carefully monitored in the older population. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether it is possible to detect decline in global scores of cognitive function in the proximity of death whilst simultaneously investigating potential risk profiles. Methods: Using the Mini Mental State Examination in a population study of the oldest old in which 99% of participants have died, a linear and quadratic time-to-death repeated measures random effects models were used to detect decline and potential factors which might indicate individual variation. Results: Decline and acceleration of this decline were detectable in the period before death. Some between person variation was detected in this pattern, which included differences in cognitive performance by age at death (-0.2 (SE=0.02)), sex (-1.2 (SE=0.2)), initial cognitive impairment (-7.5 (SE=0.2)) and mobility (-0.6 (SE=0.2)), in rate of decline by age at death (-0.04 (SE=0.005)), sex (-0.1 (SE=0.06)), initial cognitive impairment (-0.3 (SE=0.07)) and mobility (-0.1 (SE=0.05)) and differences in change in rate of decline by sex (-0.008 (SE=0.004)), initial cognitive impairment (-0.02 (SE=0.04)) and mobility (-0.01 (SE=0.003)). Conclusion: Using an extension of existing methods for exploring terminal decline, the phenomenon of decline in global cognition measures in the proximity of death was clearly detected as well as potential variables which could influence that pattern. Further work is required to explore whether similar methods can be used to detect the onset of the acceleration of this decline in each individual together with the potential to identify individual level factors that can allow clinicians to distinguish between the normal and preterminal phases of change in extreme old age. [ABSTRACT FROM AUTHOR]

An active cognitive lifestyle has been linked to dementia incidence and survival, but the separate and combined effects of its subcomponents are not clear. Data were derived from the Medical Research Council Cognitive Function and Ageing Study, a population-based study of 13,004 individuals in England and Wales first interviewed in 1991–1992 and followed over a 10-year period for dementia incidence and 12 years for mortality. A Cognitive Lifestyle Score (CLS), defined as a composite of cognitive activity including education, occupational complexity, and social engagement, was available for 12,600 individuals in 3 stages of life. A higher CLS was protective of dementia (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9). Sensitivity analyses found this main effect to be reliable and replicable even when considering just 2 components of the score, either education and occupation or education and late-life social engagement. No single CLS factor was associated with dementia incidence on its own. Survival differences did not reach statistical significance. Our data suggest that more years of education, as well as further stimulatory experiences in either midlife or late life. are necessary for a protective link with dementia incidence. There was little evidence of an effect of cognitive lifestyle on survival after dementia diagnosis. [ABSTRACT FROM PUBLISHER]

Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age. [ABSTRACT FROM AUTHOR]

Background: This study aims to establish the extent of educational differences in the disability transitions of incidence, recovery and mortality in people aged 65 years and over, whether these can be explained by differentials in disease burden and their relative contribution to educational differences in prevalence and disability-free life expectancy (DFLE).Methods: A stratified random sample of 13 004 participants in five areas in England and Wales were interviewed in 1991-94 and followed up at 2, 6 (one centre only) and 10 years. Two levels of disability were analysed: mobility difficulty and activities of daily living (ADL) disability. We fitted logistic regression models to model educational differences in disability prevalence, incidence, recovery and mortality transitions. DFLE was calculated to assess the combined effect of the dynamic transitions.Results: Those with < or =9 years education had higher ADL and mobility disability prevalence and higher incidence and lower recovery of mobility disability. Differences in disability incidence remained after adjustment for comorbidity. Women with the lowest education had shorter life expectancies (1.7 years less at the age of 65 years) than the most educated and had even shorter DFLE (1.9 years free of ADL disability and 2.8 years free of mobility difficulty at the age of 65 years).Conclusions: Differentials in education continue to contribute to prevalence of disability at ages beyond 65 years in both men and women and independently of diseases. These appear to be driven predominantly by differentials in disability incidence that also compound to produce greater differentials in DFLE between education groups than in total years lived. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with dementia.

Background: Population ageing over the first half of this century is likely to lead to dramatic increases in the prevalence of dementia. This will affect all regions of the world, but particularly developing regions. Dementia projections have been used extensively to support policy. It is therefore important these projections are as accurate as possible.Discussion: In this paper we provide a commentary on studies projecting the future prevalence of dementia for the world or for individual continents. We identify some important limitations of the methods used in published projections and provide recommendations to improve the accuracy of future projections, and allow for the checking of the accuracy of the predictions.Summary: Accurate projections of dementia incidence, at both the global and local level, are essential for healthcare planners. [ABSTRACT FROM AUTHOR]

Background: Dementia and severe cognitive impairment are very closely linked to ageing. The longer we live the more likely we are to suffer from these conditions. Given population increases in longevity it is important to understand not only risk and protective factors for dementia and severe cognitive impairment at given ages but also whether protection affects cumulative risk. This can be explored by examining the effect on cumulative risk by time of death of factors found consistently to reduce risk at particular ages, such as education and social status.Methods and Findings: In this analysis we report the prevalence of dementia and severe cognitive impairment in the year before death in a large population sample. In the Medical Research Council Cognitive Function and Ageing Study (a 10-y population-based cohort study of individuals 65 and over in England and Wales), these prevalences have been estimated by age, sex, social class, and education. Differences have been explored using logistic regression. The overall prevalence of dementia at death was 30%. There was a strong increasing trend for dementia with age from 6% for those aged 65-69 y at time of death to 58% for those aged 95 y and above at time of death. Higher prevalences were seen for severe cognitive impairment, with similar patterns. People with higher education and social class had significantly reduced dementia and severe cognitive impairment before death, but the absolute difference was small (under 10%).Conclusions: Reducing risk for dementia at a given age will lead to further extension of life, thus cumulative risk (even in populations at lower risk for given ages) remains high. Ageing of populations is likely to result in an increase in the number of people dying with dementia and severe cognitive impairment even in the presence of preventative programmes. Policy development and research for dementia must address the needs of individuals who will continue to experience these conditions before death. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported national and regional Global Burden of Disease (GBD) estimates for the UK. Because of substantial variation in health within the UK, action to improve it requires comparable estimates of disease burden and risks at country and local levels. The slowdown in the rate of improvement in life expectancy requires further investigation. We use GBD 2016 data on mortality, causes of death, and disability to analyse the burden of disease in the countries of the UK and within local authorities in England by deprivation quintile.Methods: We extracted data from the GBD 2016 to estimate years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and attributable risks from 1990 to 2016 for England, Scotland, Wales, Northern Ireland, the UK, and 150 English Upper-Tier Local Authorities. We estimated the burden of disease by cause of death, condition, year, and sex. We analysed the association between burden of disease and socioeconomic deprivation using the Index of Multiple Deprivation. We present results for all 264 GBD causes of death combined and the leading 20 specific causes, and all 84 GBD risks or risk clusters combined and 17 specific risks or risk clusters.Findings: The leading causes of age-adjusted YLLs in all UK countries in 2016 were ischaemic heart disease, lung cancers, cerebrovascular disease, and chronic obstructive pulmonary disease. Age-standardised rates of YLLs for all causes varied by two times between local areas in England according to levels of socioeconomic deprivation (from 14 274 per 100 000 population [95% uncertainty interval 12 791-15 875] in Blackpool to 6888 [6145-7739] in Wokingham). Some Upper-Tier Local Authorities, particularly those in London, did better than expected for their level of deprivation. Allowing for differences in age structure, more deprived Upper-Tier Local Authorities had higher attributable YLLs for most major risk factors in the GBD. The population attributable fractions for all-cause YLLs for individual major risk factors varied across Upper-Tier Local Authorities. Life expectancy and YLLs have improved more slowly since 2010 in all UK countries compared with 1990-2010. In nine of 150 Upper-Tier Local Authorities, YLLs increased after 2010. For attributable YLLs, the rate of improvement slowed most substantially for cardiovascular disease and breast, colorectal, and lung cancers, and showed little change for Alzheimer's disease and other dementias. Morbidity makes an increasing contribution to overall burden in the UK compared with mortality. The age-standardised UK DALY rate for low back and neck pain (1795 [1258-2356]) was higher than for ischaemic heart disease (1200 [1155-1246]) or lung cancer (660 [642-679]). The leading causes of ill health (measured through YLDs) in the UK in 2016 were low back and neck pain, skin and subcutaneous diseases, migraine, depressive disorders, and sense organ disease. Age-standardised YLD rates varied much less than equivalent YLL rates across the UK, which reflects the relative scarcity of local data on causes of ill health.Interpretation: These estimates at local, regional, and national level will allow policy makers to match resources and priorities to levels of burden and risk factors. Improvement in YLLs and life expectancy slowed notably after 2010, particularly in cardiovascular disease and cancer, and targeted actions are needed if the rate of improvement is to recover. A targeted policy response is also required to address the increasing proportion of burden due to morbidity, such as musculoskeletal problems and depression. Improving the quality and completeness of available data on these causes is an essential component of this response.Funding: Bill & Melinda Gates Foundation and Public Health England. [ABSTRACT FROM AUTHOR]

Background: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care.Methods: In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 UK [corrected] population projections.Findings: Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025.Interpretation: On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations.Funding: Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK. [ABSTRACT FROM AUTHOR]

Background: Poor micro-scale environmental features, such as graffiti and broken windows, have been associated with crime and signs of social disorder with a potential impact on mental health. The aim of this study is to investigate the association between micro-scale environment and mental health problems in later life, including cognitive (cognitive impairment and dementia) and common mental disorders (depressive and anxiety symptoms).Methods: The method of visual image audits was used to collect micro-scale environmental data for 3590 participants in the Cognitive Function and Ageing Study II, a population-based multicentre cohort of people aged 65 or above in England. Multilevel logistic regression was used to examine the associations between the quality of micro-scale environment and mental health problems taking into account urban/rural difference.Results: Poor quality of micro-scale environment was associated with nearly 20% increased odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17; 95% CI: 0.99, 1.38) while the direction of association for cognitive disorders differed across urban and rural settings. Although higher odds of cognitive disorders were found in rural settings, living in a poor quality environment was associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95% CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR: 0.80; 95% CI: 0.57, 1.11).Limitations: The causal direction could not be fully determined due to the cross-sectional nature of the data. The visual nature of the environmental assessment tool means it likely does not fully capture features related to the availability of local support services, or opportunities for social participation and interaction.Conclusions: The quality of micro-scale environment appears to be important to mental health in older people. Interventions may incorporate the environmental aspect to reduce cognitive and common mental disorders. [ABSTRACT FROM AUTHOR]