Population-based neuropathological studies of dementia: design, methods and areas of investigation--a systematic review.

BACKGROUND: Prospective population-based neuropathological studies have a special place in dementia research which is under emphasised. METHODS: A systematic review of the methods of population-based neuropathological studies of dementia was carried out. These studies were assessed in relation to their representativeness of underlying populations and the clinical, neuropsychological and neuropathological approaches adopted. RESULTS: Six studies were found to be true population-based neuropathological studies of dementia in the older people: the Hisayama study (Japan); Vantaa 85+ study (Finland); CC75C study (Cambridge, UK); CFAS (multicentre, UK); Cache County study (Utah, USA); HAAS (Hawaï, USA). These differ in the core characteristics of their populations. The studies used standardised neuropathological methods which facilitate analyses on: clinicopathological associations and confirmation of diagnosis, assessing the validity of hierarchical models of neuropathological lesion burden; investigating the associations between neuropathological burden and risk factors including genetic factors. Examples of findings are given although there is too little overlap in the areas investigated amongst these studies to form the basis of a systematic review of the results. CONCLUSION: Clinicopathological studies based on true population samples can provide unique insights in dementia. Individually they are limited in power and scope; together they represent a powerful source to translate findings from laboratory to populations

A comparison of parametric models for the investigation of the shape of cognitive change in the older population.

BACKGROUND: Cognitive decline is a major threat to well being in later life. Change scores and regression based models have often been used for its investigation. Most methods used to describe cognitive decline assume individuals lose their cognitive abilities at a constant rate with time. The investigation of the parametric curve that best describes the process has been prevented by restrictions imposed by study design limitations and methodological considerations. We propose a comparison of parametric shapes that could be considered to describe the process of cognitive decline in late life. Attrition plays a key role in the generation of missing observations in longitudinal studies of older persons. As ignoring missing observations will produce biased results and previous studies point to the important effect of the last observed cognitive score on the probability of dropout, we propose modelling both mechanisms jointly to account for these two considerations in the model likelihood. METHODS: Data from four interview waves of a population based longitudinal study of the older population, the Cambridge City over 75 Cohort Study were used. Within a selection model process, latent growth models combined with a logistic regression model for the missing data mechanism were fitted. To illustrate advantages of the model proposed, a sensitivity analysis of the missing data assumptions was conducted. RESULTS: Results showed that a quadratic curve describes cognitive decline best. Significant heterogeneity between individuals about mean curve parameters was identified. At all interviews, MMSE scores before dropout were significantly lower than those who remained in the study. Individuals with good functional ability were found to be less likely to dropout, as were women and younger persons in later stages of the study. CONCLUSION: The combination of a latent growth model with a model for the missing data has permitted to make use of all available data and quantify the effect of significant predictors of dropout on the dropout and observational processes. Cognitive decline over time in older persons is often modelled as a linear process, though we have presented other parametric curves that may be considered.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The association between late-life cognitive test scores and retrospective informant interview data

Background: Cognitive assessment of older persons, particularly those with impairment, is hampered by measurement error and the ethical issues of testing people with dementia. A potential source of valuable information about end-of-life cognitive status can be gained from those who knew the respondent well-mostly relatives or friends. This study tested the association between last cognitive assessment before death and a retrospective informant assessment of cognition. Methods: Data were analyzed from 248 participants from the Medical Research Council Cognitive Function and Ageing Study who were aged 71 to 102 years at death. Late-life cognition was assessed 0 to 8 years before death using the Mini-mental State Examination (MMSE) and the informant measure was taken 0 to 7 years after death using a Retrospective Informant Interview (RInI). Results: Zero-inflated Poisson regression showed a strong association between MMSE scores and RInI scores-those scoring 29-30 on the MMSE had a RInI score four times lower than those who scored <18 (p < 0.001). The time between MMSE and death was also a significant predictor with each additional year increasing RInI scores by 12.4% (p < 0.001). The time between death and RInI was only a significant predictor when including measures that were taken four years or more after death. Conclusions: Cognitive scores from retrospective informant interviews are strongly associated with late-life MMSE scores taken close to death. This suggests that the RInI can be used as a proxy measure of cognition in the period leading up to death. © 2010 International Psychogeriatric Association

Dementia: time trends and policy responses.

In recent years, dementia has been considered a public health priority and become a topic of major political interest. Recent reviews and studies have reported with varying degrees of alarm an impending and existing "dementia epidemic" with increasing predicted trends in prevalence and enormous numbers of people with dementia particularly in low- and middle-income countries (LMICs). However, robust evidence from dementia research in high-income countries suggests stable or decreased prevalence over the last decades. Current evidence is not sufficient to suggest increasing trends of prevalence in LMICs once variation in methodological factors and study populations are taken into account. Changes in diagnostic methods over the last decades substantially influence the identification of dementia cases with systematic difference between the resulting individual prevalence studies. Potential geographical variations at the country level might indicate potential risk factors at population levels or systematic difference in clinical application of dementia diagnosis. Although it is important and necessary to use information from dementia research for evidence-based policymaking, over-interpretation of results without carefully considering underlying factors could exaggerate the findings and influence policy planning in ways which do not serve current and future population best. Planning of dementia policy needs to take full cognisance of the provenance of the data being used and be integrated with policies which optimise health across the lifecourse.Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews was supported by the Medical Research Council [grant number U105292687].This is the accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.maturitas.2014.06.02

Prevalence of dementia in East Asia: a synthetic review of time trends.

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.There is no specific funding contributing to this study. Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews was supported by the Medical Research Council [grant number U105292687].This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/gps.4297/abstract

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

Barriers and Facilitators to the Uptake and Maintenance of Healthy Behaviours by People at Mid-Life: A Rapid Systematic Review.

BACKGROUND: With an ageing population, there is an increasing societal impact of ill health in later life. People who adopt healthy behaviours are more likely to age successfully. To engage people in health promotion initiatives in mid-life, a good understanding is needed of why people do not undertake healthy behaviours or engage in unhealthy ones. METHODS: Searches were conducted to identify systematic reviews and qualitative or longitudinal cohort studies that reported mid-life barriers and facilitators to healthy behaviours. Mid-life ranged from 40 to 64 years, but younger adults in disadvantaged or minority groups were also eligible to reflect potential earlier disease onset. Two reviewers independently conducted reference screening and study inclusion. Included studies were assessed for quality. Barriers and facilitators were identified and synthesised into broader themes to allow comparisons across behavioural risks. FINDINGS: From 16,426 titles reviewed, 28 qualitative studies, 11 longitudinal cohort studies and 46 systematic reviews were included. Evidence was found relating to uptake and maintenance of physical activity, diet and eating behaviours, smoking, alcohol, eye care, and other health promoting behaviours and grouped into six themes: health and quality of life, sociocultural factors, the physical environment, access, psychological factors, evidence relating to health inequalities. Most of the available evidence was from developed countries. Barriers that recur across different health behaviours include lack of time (due to family, household and occupational responsibilities), access issues (to transport, facilities and resources), financial costs, entrenched attitudes and behaviours, restrictions in the physical environment, low socioeconomic status, lack of knowledge. Facilitators include a focus on enjoyment, health benefits including healthy ageing, social support, clear messages, and integration of behaviours into lifestyle. Specific issues relating to population and culture were identified relating to health inequalities. CONCLUSIONS: The barriers and facilitators identified can inform the design of tailored interventions for people in mid-life.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014507

Inability to get up after falling, subsequent time on floor, and summoning help: prospective cohort study in people over 90.

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

Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy.

OBJECTIVE: To study the stability and emergence of a range of behavioural and psychological symptoms (BPS), their association with mortality and the effect of covariates on these transitions in a population-based study of cognitively impaired older people with a long follow-up period and large sample size, with a particular focus on apathy. METHODS: Data were from a population-based, longitudinal cohort study of ageing. Interviews were conducted at 0, 2, 6, 8 and 10 years with 3626 participants aged 65+. The persistence of 11 BPS and their association with mortality in those with cognitive impairment (MMSE 25 or below) was investigated using multi-state models, allowing us to take into account estimations of the probability of transitions that occurred in the time between interviews. RESULTS: Most BPS were persistent. Apathy was one of the most stable symptoms; in those with apathy, the probability of still having apathy after 1 year is 62%. Apathy, sleep problems, depression, irritability and wandering were most likely to develop. BPS are associated with mortality; in those with apathy, mortality is 3.1 times more likely than in those without apathy. Low cognitive function and dementia were associated with emergence of new symptoms. CONCLUSIONS: This population-based, multi-centre study with a follow-up period of 10 years showed that BPS are associated with mortality and most symptoms are persistent. Apathy was characterised by a high prevalence, a high persistence and a strong association with mortality, and has a negative impact on disability, management of other disease and caregiver burden.RvdL received a studentship from the National Institute for Health Research (NIHR) and the Collaborations for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire & Peterborough.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/gps.446