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Background: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. Objective: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. Methods: Twelve panellists (six experts in neurological examination, five experts in data collection—two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. Results: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. Conclusion: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist. [ABSTRACT FROM AUTHOR]

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology. [ABSTRACT FROM AUTHOR]

Background: The mental health system in Indonesia comprises attempts to modernise a colonial relic. There is still a disconnect between available services and help-seeking behaviours at the grassroots level. This study aims to explore the perceptions of Javanese people on the aetiology of mental illness and their ideas on how to deal with individuals who may have mental illness. Methods: This qualitative study involves semi-structured interviews, embedded in a cluster randomised trial examining the clinical and cost-effectiveness of primary mental health services. Interviews were conducted with Indonesian and Javanese. The recruitment procedure was aligned to the trial. Participants were primary care patients recruited from 21 sites across Yogyakarta province. Interviews were recorded, transcribed, and translated into English. Thematic analysis was used to analyse the interview transcripts. Results: 75 participants took part in the study: 51 women (68%) and 24 men (32%). Key themes emerged around perceived causes of mental health problems (including 'extrinsic factors'; 'intrinsic factors'; and 'spiritual factors'), and perceived appropriate pathways of care ('modern medical science'; 'social support and activities'; and 'religious or spiritual interventions'). Gender potentially influenced some of the responses. Conclusions: Themes indicate the variety of preconceptions towards mental health problems and assumptions regarding the best management pathways. Some of these preconceptions and assumptions support the utility of modern medical care, while the rest promote spiritual or religious healers. Participants' ideas of the appropriate care pathways largely correspond to their perception of what the symptoms are caused by. Despite hints to some understanding of the bio-psycho-social model of mental illness, most participants did not capture the complexity of mental health and illness, indicating the importance of contextual (especially culturally and religiously-aligned) public education around mental health, illness and care. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies have explored how features of the neighbourhood environment can be related to cognitive health in later life. Yet few have focused on low- and middle-income countries and compared the results across different settings. The aim of this study is to investigate the cross-sectional associations between neighbourhood amenities and dementia in older people from high-, middle- and low-income countries.Methods: This study was based on two population-based cohort studies of people aged≥65: the Cognitive Function and Ageing Study II (CFAS II) in UK (N = 4955) and a subset of the 10/66 study in China, Dominican Republic and Mexico (N = 3386). In both cohorts, dementia was assessed using the Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) algorithm. The 10/66 dementia diagnostic algorithm was also used as an additional criterion in the 10/66 study. Publicly accessible databases, Google Maps and Open Street Map, were used to obtain geographic information system data on distance to neighbourhood amenities, including lifestyle (cafés, libraries, movie theatres, parks), daily life (post offices, convenience stores), healthcare (hospitals, pharmacies) and percentages of local green and blue spaces within 400 and 800 m of participants' residences. Multilevel logistic regression was used to investigate the associations between these environmental features and dementia adjusting for sociodemographic factors and self-rated health.Results: Living far from daily life amenities was associated with higher odds of dementia in both CFAS II (1.47; 95% CI: 0.96, 2.24) and the 10/66 study (1.53; 95% CI: 1.15, 2.04), while living far from lifestyle (1.50; 95% CI: 1.13, 1.99) and healthcare amenities (1.32; 95% CI: 0.93, 1.87) was associated with higher odds of dementia only in the 10/66 study. A high availability of local green and blue spaces was not associated with dementia in either cohort yet living far from public parks was associated with lower odds of dementia in CFAS II (0.64; 95% CI: 0.41, 1.00).Conclusions: The different relationships across cohorts may indicate a varying role for local amenities in diverse settings. Future research may investigate mechanisms related to these differences and social, cultural and historical influences on the interaction between neighbourhood amenities and older people. [ABSTRACT FROM AUTHOR]

Background: Studies from North America and Western Europe suggest stable or declining trends in impaired cognition across birth cohorts.Objective: We aimed to examine changes in the age-specific prevalence of cognitive impairment in the Czech Republic.Methods: The study used two samples from the population-based Czech Survey on Health, Ageing and Retirement in Europe. Age-specific prevalence of cognitive impairment (defined based on scores in verbal fluency, immediate recall, delayed recall, and temporal orientation) was compared between participants in wave 2 (2006/2007; n = 1,107) and wave 6 (2015; n = 3,104). Logistic regression was used to estimate the association between the wave and cognitive impairment, step-wise adjusting for sociodemographic and clinical characteristics. Multiple sensitivity analyses, focusing on alternative operationalizations of relative cognitive impairment, impact of missing cognitive data, and survival bias, were carried out.Results: The most conservative estimate suggested that the age-specific prevalence of cognitive impairment declined by one fifth, from 11% in 2006/2007 to 9% in 2015. Decline was observed in all sensitivity analyses. The change was associated with differences in physical inactivity, management of high blood cholesterol, and increases in length education.Conclusion: Older adults in the Czech Republic, a country situated in the Central and Eastern European region, have achieved positive developments in cognitive aging. Longer education, better management of cardiovascular factors, and reduced physical inactivity seem to be of key importance. [ABSTRACT FROM AUTHOR]

This raises the question whether the previous phase III trials, which were generally neutral, were simply performed too soon with insufficient development of combinations of effective interventions, and the current studies prepare the ground for large scale phase III trials with a higher chance of success. But while the SMARRT trial targets persons between 70 and 89, the AIBL and MYB studies target much younger populations of over 60 and 55-77, respectively [[5]]. Although the SMARRT pilot trial will use change in cognitive functioning for the sample size calculation for the full-scale trial, it will potentially be able to power for all-cause dementia due to the target age range of 70-89, depending on the expected effect size and planned study duration of the full trial. The AIBL proof of concept for sustainable adherence, the carefully designed pilot study necessary for a proper sample size calculation in SMARRT, and the ambitious MYB study may all inspire future dementia prevention study designs. [Extracted from the article]

Background: Research into Alzheimer's disease and other dementias increasingly involves large-scale data-sharing initiatives. The development of novel digital tools and assessments is likely to increase the need for these. This presents ethics and governance challenges to ensure the use of these data is able to maximise the benefit to patients and the public. Discussion: We consider the challenges associated with informed consent and governance in the context of dementia research. We set out the potential of novel data governance approaches for the future of data sharing for dementia. Summary: The data trust model proposed in discussions of data governance may have potentially valuable application for dementia research. Such inclusive approaches to trustworthy data governance should be considered as data-sharing initiatives are established and develop. [ABSTRACT FROM AUTHOR]

In this month's Editorial, Guest Editors Carol Brayne and Bruce Miller discuss research and commentary published in March and future directions for dementia research. [ABSTRACT FROM AUTHOR]

Objectives To determine the prevalence of dementia and cognitive impairment in older people across generations. Design Two prospective cohort studies (Personnes Agées QUID ( PAQUID), Aging Multidisciplinary Investigation ( AMI)). Setting Baseline data from two subsamples of older farmers in southwestern France. Participants PAQUID (n = 595) and AMI (n = 906) participants aged 65 and older living at home at baseline (1988 PAQUID, 2008 AMI). Measurements Two methods were used to diagnose dementia: a clinical consensus diagnosis and a computer-assisted taxonomy approach (cognitive impairment with disability ( CIWD)) using Mini-Mental State Examination and instrumental activity of daily living scores. Crude and standardized prevalences (using PAQUID age-sex structure) and 95% confidence intervals were calculated, and logistic regression was used to explore confounding. Results The prevalence of consensus diagnosis of dementia was higher in AMI in 2008 than in PAQUID in 1988 (12.0% vs 5.7%, P < .001), whereas the reverse was observed for CIWD (14.8% vs 23.8%, P < .001), confirmed by logistic regressions (odds ratio ( OR) AMIvs PAQUID = 2.50, 95% confidence interval ( CI) = 1.52-4.12; ORAMIvs. PAQUID = 0.60, 95% CI = 0.42-0.87, respectively). Educational level increased and management of vascular risk factors improved over the study period, and health and living conditions improved globally. Conclusion These findings suggest global cognitive and functional improvement in old farmers (the prevalence of CIWD decreased by 40% over 20 years) and simultaneously a marked change in the subjective boundary between dementia and nondementia according to clinicians. [ABSTRACT FROM AUTHOR]

Background A fragmented research field exists on the prevalence of anxiety disorders. Here, we present the results of a systematic review of reviews on this topic. We included the highest quality studies to inform practice and policy on this issue. Method Using PRISMA methodology, extensive electronic and manual citation searches were performed to identify relevant reviews. Screening, data extraction, and quality assessment were undertaken by two reviewers. Inclusion criteria consisted of systematic reviews or meta-analyses on the prevalence of anxiety disorders that fulfilled at least half of the AMSTAR quality criteria. Results We identified a total of 48 reviews and described the prevalence of anxiety across population subgroups and settings, as reported by these studies. Despite the high heterogeneity of prevalence estimates across primary studies, there was emerging and compelling evidence of substantial prevalence of anxiety disorders generally (3.8-25%), and particularly in women (5.2-8.7%); young adults (2.5-9.1%); people with chronic diseases (1.4-70%); and individuals from Euro/Anglo cultures (3.8-10.4%) versus individuals from Indo/Asian (2.8%), African (4.4%), Central/Eastern European (3.2%), North African/Middle Eastern (4.9%), and Ibero/Latin cultures (6.2%). Conclusions The prevalence of anxiety disorders is high in population subgroups across the globe. Recent research has expanded its focus to Asian countries, an increasingly greater number of physical and psychiatric conditions, and traumatic events associated with anxiety. Further research on illness trajectories and anxiety levels pre- and post-treatment is needed. Few studies have been conducted in developing and under-developed parts of the world and have little representation in the global literature. [ABSTRACT FROM AUTHOR]

Background/Aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. Results: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective This study aims to synthesise evidence on time trends of dementia prevalence in East Asian countries including Japan, China, South Korea and Taiwan and assess the impact of the societal changes on future prevalence. Method Relevant reviews and recent nationwide studies in East Asia were identified to investigate changes in prevalence of dementia over time taking into account the potential impact of methodological factors and study designs. Results The robust evidence that has been interpreted to suggest a substantial increasing trend over time is less compelling once fundamental differences in study methods and populations across individual surveys are considered. In Japan, longitudinal studies in small areas suggest the potential increase of prevalence after 2000. Increasing trends in China, South Korea and Taiwan over the last 20-30 years are based on the literature review without adjustment for methodological differences. Economic development and huge societal changes alongside the rise of non-communicable disease in East Asia could lead to increasing prevalence of dementia in the future once those cohorts with high risk of dementia reached their older age. Conclusion Current evidence is not sufficient to suggest increasing trends of dementia prevalence in East Asia. Longitudinal studies with representative samples and stable methodology are needed to provide fundamental information of the epidemiology of dementia and identify important risk factors in East Asian societies. © 2015 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Studies with strong selection biases propose that alpha-synucleinopathy (AS) spreads upwards and downwards in the neuraxis from the medulla, that amygdala-dominant AS is strongly associated with Alzheimer's disease (AD), and that a more severe involvement of the cerebral cortex is correlated with increasing risk of dementia. This study examines the association of AS patterns and observed neuropsychological symptoms in brains of a population-representative donor cohort. Methods: Brains donated in 2 out of 6 cognitive function and ageing study cohorts (Cambridgeshire and Nottingham) were examined. Over 80% were >80 years old at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein (using LB509 by Zymed Laboratories) was carried out in 208 brains to establish Braak stage and the pattern and severity of AS following the dementia with Lewy bodies (DLB) consensus recommendations. Dementia, specific neuropsychological measures as measured using the Cambridge cognitive examination, the presence of hallucinations and Parkinson's disease were investigated. Results: Four patterns of AS were observed: no AS pathology (n = 92), AS pathology following the DLB consensus guidelines (n = 33, of which five were 'neocortical'), amygdala-predominant AS (n = 18), and other AS patterns (n = 33). Each group was subdivided according to high/low neurofibrillary tangles (NFT) Braak stage. Results showed no association between dementia and these patterns of AS, adjusting for the presence of NFT or not. The risk of visual hallucinations shows a weak association with AS in the substantia nigra (odds ratio (OR) = 3.2; 95% confidence interval (CI) 0.5 to 15.5; P = 0.09) and amygdala (OR = 3.0; 95% CI 0.7 to 12.3; P = 0.07). The analysis is similar for auditory hallucinations in subcortical regions. Conclusions: Among the whole population of older people, AS does not increase the risks for dementia, irrespective of Braak stage of NFT pathology. There was no evidence that the pattern of AS pathology in cortical areas was relevant to the risk of hallucination. In general, the hypothesis that AS as measured using these methods per se is a key determinant of cognitive clinical phenotypes is not supported. [ABSTRACT FROM AUTHOR]

Accurate detection of individuals with cognitive impairment and dementia in addition to identification of those at high risk of future disease is important to guide clinical care, and has research implications regarding clinical trial recruitment and development of dementia preventative strategies. In this narrative review, we describe new proposed criteria for early diagnosis of Alzheimer's disease (AD). We also explore risk factors for dementia and evaluate methods for screening for increased risk of incident disease. We highlight variability in different diagnostic approaches. Additional work needs to be done to validate new methods across different settings (such as population-based, primary care, and memory clinics), age, and ethnic groups. Having an accurate method to assess for dementia and predict risk in routine clinical care will aid decision making and could ultimately lead to disease prevention. [ABSTRACT FROM AUTHOR]

Abstract: Dementia research over the last 50 years has expanded enormously and has greater international interest now than at any time in history. A variety of scientific approaches have been brought to bear on this complex disorder in which the syndrome of clinical features is its defining importance in societal terms. Little has emerged in terms of tangible benefits for people with dementia to date other than a hugely increased awareness at societal and governmental levels. One of the drivers for the increase in focus has been epidemiological evidence, which has provided background numbers for the justification of resources for dementia research. However it can be argued that this justification did not take into account the true meaning of the population evidence, drawing instead on preconceptions which were, at the time, the widely accepted interpretations of earlier evidence. Current evidence, along with the lack of single therapeutic successes, suggests that a clearer analysis is required which not only examines the value and applicability of existing knowledge, most particularly its generation and generalizability, but also where future investment should go for most likely benefit of populations. This includes a hard look at the pre-occupation of societies with single therapies, their place in the context of prevention more generally, particularly within aging populations, and how evidence is generated on likely impacts and their timeframes. [Copyright &y& Elsevier]

Six papers based on studies with particular epidemiological designs are presented here which have been selected on the basis of their visibility in the literature. The designs are intended to provide robust evidence on risk, natural history, and underpinning neurobiology and outcomes relevant to aging populations. There is a large case control study (the Late Onset Alzheimer's Disease study), a case cohort study of Parkinson's Disease (the CamPaIGN study), and the Medical Research Council Cognitive Function and Ageing Study. Each study has included genetic investigation and risk, and the latter two include investigation of the clinical syndromes and their natural histories in relation to underlying pathology. Each aimed to provide results which were as generalizable to usual older populations as possible and each has produced findings which have contributed to current understanding of genetic risk, the heterogeneity of the syndrome of Parkinson's disease, and the underlying neuropathology of dementia in older population. They have influenced thinking about future directions, and the cohorts on which the findings are based will continue to provide an important resource for novel areas of research and future health care planning. [ABSTRACT FROM AUTHOR]

A disconnect has developed over the past two decades between neurological and neuroscientific research, which have seen notable innovation and development, and our increasing understanding of the role of social and commercial determinants of health, including the health of the nervous system. Over the next two decades, grounding neurological research in public health and epidemiological principles can bring about a paradigm shift, away from reductionism, over-medicalisation, and health inequities towards neurological research that reduces inequalities and has true relevance to the populations it aims to serve. People who are involved in neurological and neuroscientific research and practice, as clinicians, researchers, publishers, and funders, can create change by being more aware of the social and commercial determinants of health, reprioritising research funding, and advocating for greater neurological health equity. [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]

We here describe the study-design major findings from the neuropathological component of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS). MRC CFAS is a population-representative study of aging and health including more than 18000 participants at baseline. More than 500 brain donations were accrued to date and have been subjected to comprehensive pathological assessment. This resource enables a thorough epidemiological description of the neuropathology associated with dementia in the UK. Results to date reveal a high prevalence of mixed Alzheimer and vascular pathology, a significant population who die with dementia but with a more limited pathological burden than is traditionally associated with dementia, and a group who die with a significant pathological burden yet remained cognitively intact until death. This dissociation between pathology and dementia increases with increasing age. Further studies have described the distribution and etiology of neurodegenerative disease in the population, and determined pathological correlates of cognitive impairment and dementia. Brain donation programs linked to epidemiological studies provide an invaluable resource for describing the pathological correlates of dementia in a way that is representative of the population, thereby identifying targets for and assessing the likely effect of therapeutic and preventive interventions. [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]

The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques-which are frequently surrounded by dystrophic neurites-and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: A recent genome-wide association (GWA) study of late-onset Alzheimer’s disease (LOAD) identified 15 novel single nucleotide polymorphisms (SNPs) independent of ApoE. We hypothesised that variants associated with LOAD are also associated with poor cognitive function in elderly populations. We measured additive associations between the five most strongly associated LOAD SNPs and grouped Mini Mental State Examination (MMSE) scores. Variants were genotyped in respondents (mean age 79 years) from the Oxford Healthy Ageing project (OHAP) and other sites of the MRC Cognitive Function and Ageing Study (MRC-CFAS). In adjusted ordinal logistic models, two variants were associated with poorer cognitive function: rs11622883 (OR=1.14, 95% CI: 1.01–1.28, p =0.040) and rs505058 (OR=1.29, 95% CI: 1.02–1.64, p =0.036). These SNPs are close to a SERPINA gene cluster and within LMNA, respectively. The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment. [Copyright &y& Elsevier]

The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in an investigation of the relationships of brain pathology at death, clinical dementia and time in education, testing the hypothesis that greater exposure to education reduces the risk of dementia. EClipSE has harmonized longitudinal clinical data and neuropathology from three longstanding population-based studies that included post-mortem brain donation. These three studies started between 1985 and 1991. Number of years of education during earlier life was recorded at baseline. Incident dementia was detected through follow-up interviews, complemented by retrospective informant interviews, death certificate data and linked health/social records (dependent on study) after death. Dementia-related neuropathologies were assessed in each study in a comparable manner based on the Consortium to Establish a Registry for Alzheimer's Disease protocol. Eight hundred and seventy-two brain donors were included, of whom 56% were demented at death. Longer years in education were associated with decreased dementia risk and greater brain weight but had no relationship to neurodegenerative or vascular pathologies. The associations between neuropathological variables and clinical dementia differed according to the ‘dose’ of education such that more education reduced dementia risk largely independently of severity of pathology. More education did not protect individuals from developing neurodegenerative and vascular neuropathology by the time they died but it did appear to mitigate the impact of pathology on the clinical expression of dementia before death. The findings suggest that an understanding of the mechanisms leading to functional protection in the presence of pathology may be of considerable value to society. [ABSTRACT FROM AUTHOR]

Aim: Non-hypolipidemic effects of statins, known as pleiotropic effects, are likely to explain the effect of statins on dementia. Results of the relationship between statins and dementia in previous studies are conflicting. There is no systematic review investigating the effect of statins on vascular dementia (VaD). This systematic review evaluates the role of statins in the prevention of VaD or dementia. The possible causes of conflicting results in the existing published work will be explored. Methods: Relevant studies were systematically identified and reviewed. The Cochrane Controlled Trials and three electronic databases (MEDLINE, EMBASE and PsycInfo) were searched. The selection criteria were defined a priori. Included studies were rated by quality assessment checklists and two independent reviewers. Results: Six studies in dementia, two studies in VaD (one study reported both dementia and VaD) and two meta-analyses met the selection criteria. The studies covered 1372 cases of dementia from 14 430 participants and 116 cases of VaD from 4924 participants from the USA and UK. There was no association between statin use and risk of VaD. The protective effect of statins on dementia was demonstrated only in a nested case–control study of lower quality and one recently published cohort study. In most other cohort and high quality studies, statin use did not show a beneficial effect. Conclusion: Study design differences among the studies and methodological shortcomings may have resulted in different outcomes. On the basis of these conflicting results, statins could not be recommended as a preventative treatment for dementia. [ABSTRACT FROM AUTHOR]

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: Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS). Methods and Findings: A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%). Conclusions: Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively ''pure,'' but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia. [ABSTRACT FROM AUTHOR]

Objectives To describe the incidence and extent of lying on the floor for a long time after being unable to get up from a fall among people aged over 90; to explore their use of call alarm systems in these circumstances. Design 1 year follow-up of participants in a prospective cohort study of ageing, using fall calendars, phone calls, and visits. Setting Participants' usual place of residence (own homes or care homes), mostly in Cambridge. Participants 90 women and 20 men aged over 90 (n=110), surviving participants of the Cambridge City over-75s Cohort, a population based sample. Main outcome measures Inability to get up without help, lying on floor for a long time after falling, associated factors; availability and use of call alarm systems; participants' views on using call alarms to summon help if needed after falling. Results In one year's intensive follow-up, 54% (144/265) of fall reports described the participant as being found on the floor and 82% (217/265) of falls occurred when the person was alone. Of the 60% who fell, 80% (53./66) were unable to get up after at least one fall and 30% (20/66) had lain on the floor for an hour or more. Difficulty in getting up was consistently associated with age, reported mobility, and severe cognitive impairment. Cognition was the only characteristic that predicted lying on the floor for a long time. Lying on the floor for a long time was strongly associated with serious injuries, admission to hospital, and subsequent moves into long term care. Call alarms were widely available but were not used in most cases of falls that led to lying on the floor for a long time. Comments from older people and carers showed the complexity of issues around the use of call alarms, including perceptions of irrelevance, concerns about independence, and practical difficulties. Conclusions Lying on the floor for a long time after falling is more common among the "oldest old" than previously thought and is associated with serious consequences. Factors indicating higher risk and comments from participants suggest practical implications. People need training in strategies to get up from the floor. Work is needed on access and activation issues for design of call alarms and information for their effective use. Care providers need better understanding of the perceptions of older people to provide acceptable support services. [ABSTRACT FROM AUTHOR]

Objectives Classifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ‘at-risk’ cases in the application of different MCI criteria in the population is unknown. Methods Data were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated. Results Prevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5–41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7–30.0%), reflecting heterogeneity in MCI classification requirements. Conclusions Narrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ‘normal’, over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The identification of modifiable risk factors that prevent dementia or slow its progression is a major public health priority. Vascular disease and its risk factors have been linked with cognitive decline and dementia, although the degree of association varies depending on differences in vulnerability related to age, ethnicity, disease co-morbidity and possibly brain reserve. Here we review current dementia prevention strategies linked to vascular modification to identify whether any approach exists that will reduce the population burden of dementia, and whether any exist that show evidence of being cost effective and safe for populations. As yet, there is no compelling evidence that dementia can be prevented through vascular manipulation by pharmacological or non-pharmacological trials. To date, no intervention can be recommended for dementia prevention at the population level including Alzheimer's Disease or Vascular Dementia. Advances in the prevention of dementia will be gained, it is argued, from a more complete understanding of the pathophysiology of disease and its causes, particularly in early life, within and across different populations and age groups. Furthermore, a more complete understanding of the earliest pre-clinical stage of disease is required for effective risk factor modification. Although the current state of knowledge cannot support public health policy for vascular manipulation for dementia prevention at the population level, this does not undermine the importance of vascular manipulation in its own right to promote healthier ageing. [ABSTRACT FROM AUTHOR]

Objectives To provide estimates of survival after onset of dementia by age, sex, self reported health, disability, and severity of cognitive impairment. Design Analysis of participants from prospective population based cohort study in 1991-2003, with follow- up of dementia status in all individuals after two and six years (in one centre) and 10 years and in subsamples additionally at six and eight years and mortality until 2005. Setting Multicentre population based study in England and Wales: two rural and three urban centres. Participants 438 participants who developed dementia from a population based study of 13 004 individuals aged 65 years and over drawn from primary care population registers. Main outcome measures Sociodemographic factors, cognitive function, specific health conditions, and self reported health collected at each interview. Cox's proportional hazards regression models were used to identify predictors of mortality from the selected variables in people who received diagnosis of dementia according the study's criteria. Results By December 2005, 356 of the 438 (81%) participants who developed dementia during the study had died. Estimated median survival time from onset of dementia to death was 4.1 years (interquartile range 2.5-7.6) for men and 4.6 years (2.9-7.0) for women. There was a difference of nearly seven years in survival between the younger old and the oldest people with dementia: 10.7 (25th centile 5.6) forages 65-69; 5.4 (interquartile range 3.4-8.3) for ages 70-79; 4.3 (2.8-7.0) for ages 80-89, and 3.8 (2.3-5.2) years for ages >90. Significant factors that predicted mortality in the presence of dementia during the follow-up included sex, age of onset, and disability. Conclusion These analyses give a population based estimated median survival for incident dementia of 4.5 years. Such estimates can be used for prognosis and planningfor patients, carers, service providers, and policy makers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Numerous studies report a positive association between the presence of vascular conditions and depression; however, it is unclear whether this presents a distinct subtype of depression. Method: A comprehensive literature search of Medline was conducted in order to identify studies that have compared symptoms of those with depression in the presence and absence of vascular factors. Aims: To provide a systematic review of studies that have attempted to characterise the depressive symptomatology associated with vascular factors. To establish whether the evidence for a subtype is sufficient to be of use in clinical settings. Results: Thirteen publications were identified as relevant to the investigation. Study design and definition of vascular factors varied greatly between studies. Depression in the presence of vascular conditions was associated with poor motivation, lack of energy and psychomotor change in some studies, though these findings were inconsistent. Many other possible distinctive features were reported in individual publications but were not consistent enough to be used confidently as a diagnostic feature. Conclusion: At present, there does not appear to be sufficient evidence to support a clinically-recognisable subtype of vascular depression. [Copyright &y& Elsevier]

The increasing age of the population around the world has meant that greater attention is being paid to disorders that mainly affect older people. In particular, work is focusing on ways to preserve the healthy brain and prevent dementia. Preventive studies are complex and must take into account not only simple approaches such as those used in risk and outcome studies, but also stage of life, survival and mortality, and population context before their effect can be assessed. This paper presents questions and areas which must be explored if the potential for prevention of dementia during brain ageing is to be properly understood. [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]

Rigid and introverted personality type has been suggested as possibly associated with risk of Parkinson's disease (PD). However, to be a risk, the measurement of personality must precede the onset of PD, more than simply reported as personality in PD cases. Several reviews have been published examining the literature base for this suggestion; however, the issue of 'premorbid' personality measurement was not emphasized. MEDLINE, EMBASE, and PSYCHINFO databases were searched for existing systematic reviews or meta-analyses, and none were found that fulfilled this criterion. The databases were searched systematically for primary research articles. Articles without robust methodology were excluded based on published quality scoring criteria. No articles met all selection criteria. Four articles met most selection criteria and three of them reported significant differences in personality features said to be present before PD onset and between PD cases and controls. PD cases were more introverted, cautious, socially alert, and tense than controls. Although the instruments used to characterize personality varied widely across studies, the general descriptions of PD patients included nervous, cautious, rigid, and conventional. There do appear to be parkinsonian characteristics, but these studies were all retrospective. To confirm that personality traits precede PD onset and are a risk for this condition, prospective research is required. Even then, the term 'premorbid' is difficult to define due to the unknown latent period before onset of PD. Additional research would involve correlating personality characteristics to activities or changes in the brain. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objective: to investigate a number of prospectively collected factors (sociodemographic, medical and behavioural) and their association with incident dementia in a population based cohort. Design: nested case-control analysis (at 2 and 6 years) of a population-based cohort study. Setting: individuals aged 65 years and above from five centres in England and Wales: two rural (Cambridgeshire and Gwynedd) and three urban (Nottingham, Newcastle and Oxford). Participants: a total of 4,075 individuals from a detailed assessment group, with risk measured at baseline. Main outcome measure: incident dementia at 2 and 6 years. Methods: logistic regression was used to calculate crude odds ratios (ORs) for various risk factors and ORs adjusted for age, sex, education and social class. Results: age (90+ versus 65-69 years OR = 25.6, 95% confidence interval (CI) = 11.6-56.9) and sex (women versus men OR = 1.6, 95% CI = 1.1-2.4) were directly associated with dementia, with a trend by years of education (Ptrend = 0.02) but not social class. Poor self-perceived health (versus good) increased the risk for incident dementia (OR = 3.9, 95%, CI = 2.2-5.9). Alcohol and smoking (never, past and current) were neither strongly protective nor predictive. Stroke was strongly related to incident dementia (OR = 2.1, 95% CI = 1.1-4.2), as was Parkinson's disease (OR = 3.5, 95% CI = 1.3-9.3), and exposure to general anaesthesia (GA) was inversely associated with dementia development (OR = 0.6, 95% CI = 0.4-0.9, with a trend with increasing GA exposure; P = 0.003). Conclusion: in this large multicentre and long-term population-based study, some well-known risk factors for dementia, of vascular and Alzheimer's type, are confirmed but not others. The association between self-perceived health--a robust predictor of later health outcomes--and incident dementia, independently of other potential risks, warrants further study. [ABSTRACT FROM AUTHOR]

This review examines the evidence for screening for autism spectrum disorders in the general population and the information needed to inform screening policy. The UK National Screening Committee criteria are taken as the framework. These criteria cover the condition, the screening test, the treatment and the screening programme as a whole. With respect to the condition, reasons for variation in prevalence estimates for autism spectrum disorders need to be resolved and there are few longitudinal studies to describe the natural history of autism spectrum disorders that include data on children identified at an early age. There is no screening test suitable for use in a population setting that has been fully validated. There is insufficient evidence regarding the effectiveness of interventions. This review supports the current policy position of the National Screening Committee, that on the basis of existing evidence, screening for autism spectrum disorders cannot be recommended. [ABSTRACT FROM AUTHOR]

Abstract: There are many challenges facing epidemiologists wishing to investigate relationships between physical activity, obesity, diabetes, dementia and depression, all of which are complex fields in their own right. There is a large literature investigating the relationship between diabetes and dementia but less, as yet, on the other exposures and outcomes. In this literature there is a diversity of definitions making rigorous systematic review problematic. There is a need to define hypotheses in this area very clearly and to identify studies that have addressed the specific question. Such exercises have not been carried out to date but would enlighten the research area and point more clearly to questions which remain to be answered. Our own research group has examined the specific question of risk of development of dementia in relation to levels of HbA1c, as a marker of glycaemic control and showed that although not related to dementia, it is related to incidence of severe cognitive impairment. [Copyright &y& Elsevier]

Background: Although incidence of dementia is known to vary between nations, variation within country has not been explored because most incidence studies are single site or have insufficient numbers to compare sites. Few countries have conducted multisite incidence studies in order to facilitate national comparisons. This study aims to provide robust measures of the variation of the incidence of dementia across sites within England and Wales and produce overall estimates by age and sex. Methods and Findings: The Medical Research Council Cognitive Function and Ageing Study used identical methodology in five diverse sites across the United Kingdom, each with different risk patterns and mortality rates. Incidence has been estimated using likelihood-based methods between the first two waves of interviews. Incidence rates rise with age, particularly above the age of 75 y, from 7.4 (95% confidence interval, 3.6-16.1) per 1,000 person years at age 65-69 y to 84.9 (95% confidence interval, 63.0-107.8) per 1,000 person years at age 85 y and above. The rate of increase for both sexes is marked, and continues into the oldest age groups. Hence, it is estimated that approximately 180,000 new cases of dementia occur in England and Wales each year. There is no convincing evidence of variation across sites, and incidence rates do not reflect the variations in the prevalence of possible risk factors in these sites. Conclusion: There is no evidence, within England and Wales, of variation in dementia incidence across sites. Dementia incidence rates do not tail off at the oldest ages. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Longitudinal studies of the elderly are complicated by the loss of individuals between waves due to death or other dropout mechanisms. Factors that affect dropout may well be similar from one study to another. This article systematically reviews all large population-based studies of the elderly (published 1966–2002) that report on differences in individual characteristics between people who remain and people who dropout at follow-up. Study design and setting: A systematic review of articles that investigate attrition after baseline interview. Results: Twelve studies were found that investigated dropout other than death using unadjusted, multivariable methods or both. The unadjusted analyses showed many significant factors related to attrition. Multivariable analyses showed two main independent factors were related to increased attrition: increasing age and cognitive impairment. People who were very ill or frail had higher dropout rates, and people in worse health were less likely to be recontactable. Conclusions: Multivariable methods of analyzing attrition in longitudinal studies show consistent patterns of dropout between differing studies, with a small number of key relationships. These findings will assist researchers when planning studies of older people, and provide insight into the possible biases in longitudinal studies introduced by differential dropout. [Copyright &y& Elsevier]

The analysis of longitudinal data has recently been an active area of biostatistical research. Two main approaches to analysis have emerged, the first concentrating on modelling evolution of marginal distributions of the main response variable of interest and the other on subject-specific trajectories. In epidemiology the analysis is usually complicated by missing data and by death of study participants. Motivated by a study of cognitive decline in the elderly, this paper argues that these two types of incomplete follow-up may need to be treated differently in the analysis, and proposes an extension to the marginal modelling approach. The problem of informative drop-out is also discussed. The methods are implemented in the 'Stata' statistical package. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Focuses on a study which provided a profile of disorders and disabilities in the older population. Setting and design of the study; Results; Conclusion.