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Background: Air pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK. Methods: This study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008–2011) and Wales (2011–2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO2, O3, PM10, PM2.5) were modelled for the year 2012 and linked via the participants' postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies. Results: Higher exposure levels of NO2 (HR: 1.04; 95% CI: 0.94, 1.14), O3 (HR: 0.90; 95% CI: 0.70, 1.15), PM10 (HR: 1.17; 95% CI: 0.86, 1.58), PM2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies. Conclusions: In contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse. [ABSTRACT FROM AUTHOR]

Background and Objectives A 2008 European consensus on research outcome measures in dementia care concluded that measurement of carer quality of life (QoL) was limited. Three systematic reviews (2012, 2017, and 2018) of dementia carer outcome measures found existing instruments wanting. In 2017, recommendations were published for developing reliable measurement tools of carers' needs for research and clinical application. The aim of this study was to develop a new instrument to measure the QoL of dementia carers (family/friends). Methods Items were generated directly from carers following an inductive needs-led approach. Carers (n = 566) from 22 English and Welsh locations then completed the items and comparator measures at three time points. Rasch, factor, and psychometric (reliability, validity, responsiveness, and minimally important differences [MIDs]) analyses were undertaken. Results Following factor analysis, the pool of 70 items was refined to three independent scales: primary SIDECAR-D (direct impact of caring upon carer QOL, 18 items), secondary SIDECAR-I (indirect impact, 10 items), and SIDECAR-S (support and information, 11 items). All three scales satisfy Rasch model assumptions. SIDECAR-D, I, S psychometrics: reliability (internal ≥.70; test–retest ≥.85); convergent validity (as hypothesized); responsiveness (effect sizes: D: moderate; I and S: small); MIDs (D = 9/100, I = 10/100, S = 11/100). Discussion and Implications SIDECAR scales demonstrate robust measurement properties, meeting COSMIN quality standards for study design and psychometrics. SIDECAR provides a theoretically based needs-led QoL profile specifically for dementia carers. SIDECAR is free for use in public health, social care, and voluntary sector services, and not-for-profit organizations. [ABSTRACT FROM AUTHOR]

Background: death certification data are routinely collected in most developed countries. Coded causes of death are a readily accessible source and have the potential advantage of providing complete follow-up, but with limitations. Objective: to investigate the reliability of using death certificates for surveillance of dementia, the time trend of recording dementia on death certificates and predictive factors of recording of dementia. Subjects: individuals aged 65 and over in six areas across England and Wales were randomly selected for the Medical Research Council Cognitive Function and Ageing Study (CFAS) and CFAS II with mortality follow-up. Methods: prevalence of dementia recorded on death certificates were calculated by year. Reporting of dementia on death certificates compared with the study diagnosis of dementia, with sensitivity, specificity and Cohen's x were estimated. Multivariable logistic regression models explored the impact of potential factors on the reporting of dementia on the death certificate. Results: the overall unadjusted prevalence of dementia on death certificates rose from 5.3% to 25.9% over the last 26 years. Dementia reported on death certificates was poor with sensitivity 21.0% in earlier cohort CFAS, but it had increased to 45.2% in CFAS II. Dementia was more likely to be recorded on death certificates in individuals with severe dementia, or those living in an institution, yet less likely reported if individuals died in hospital. Conclusion: recording dementia on death certificate has improved significantly in the England and Wales. However, such information is still an underestimate and should be used alongside epidemiological estimations. [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]

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]

Background: Whilst many studies have analysed predictors of longitudinal cognitive decline, few have described their impact on population distributions of cognition by age cohort. The aim of this paper was to examine whether gender, education, social class and birth cohort affect how mean population cognition changes with age. Methods: The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is a multi-centre population based longitudinal study of 13,004 individuals in England and Wales. Using ten years of follow-up data, mean Mini-mental State Examination (MMSE) scores were modelled by age and birth cohort adjusting for nonrandom drop-out. The model included terms to estimate cohort effects. Results are presented for five year age bands between 65-95 years. Results: At a population level, women show greater change in MMSE scores with age than men. Populations with lower education level and manual work also show similar effects. More recent birth cohorts have slightly higher scores. Conclusion: Longitudinal data can allow examination of population patterns by gender, educational level, social class and cohort. Each of these major socio-demographic factors shows some effect on whole population change in MMSE with age. [ABSTRACT FROM AUTHOR]

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]

Background: Behavioural and psychological symptoms of dementia (BPSD) are major contributors to the burden of dementia.Aims: To describe the prevalence, correlates and course of BPSD in the population of England and Wales.Method: The prevalence of 12 symptoms was estimated in 587 participants with dementia and 2050 participants without dementia as part of a population-based longitudinal study of ageing. The effect of risk factors and the factor structure were estimated using 1782 interviews provided by participants with dementia throughout the study.Results: Each symptom apart from sleeping problems was more common in the population with dementia. The co-occurrence of the symptoms was explained by a four-factor solution, corresponding to psychosis/apathy, depression/anxiety, irritability/persecution and wandering/sleep problems. Psychosis occurred more frequently with declining cognition. Anxiety and depression were more common in younger individuals and in those with poor self-reported health. Persistence varied between symptoms.Conclusions: Behavioural and psychological symptoms of dementia affect nearly all people with dementia. Symptoms co-occur, and the symptoms that affected individuals experience are related to their socio-demographic and clinical characteristics. [ABSTRACT FROM AUTHOR]

Objective: to describe the characteristics and survival of the oldest old in England and Wales. Design: retrospective analysis of the oldest old from a population-based cohort study. Setting: population-based study in England and Wales: two rural and three urban sites. Methods: two types of analyses were conducted: (i) a descriptive analysis of those individuals who were aged 90 years or more, and 100 years or more, and (ii) a survival analysis of those who reached their 90th, 95th, or 100th birthday during the study. Median survival time was calculated by the Kaplan-Meier method. Effects of socio-demographic characteristics on survival were evaluated using the Cox proportional-hazards regression model. Results: in total, 958 individuals aged 90 years or more, and 24 individuals aged 100 years or more, had been interviewed at least once during the study. Twenty-seven per cent were living in residential or nursing homes. Women aged 90 years or more were more likely to be living in residential and nursing homes, be widowed, have any disability or have lower MMSE scores. The centenarians were mostly cognitively and functionally impaired. The median survival times for those reaching their 90th (n = 2,336), 95th (n = 638), or 100th birthday (n = 92) during the study were 3.7 years (95% CI: 3.5-4.0), 2.3 (2.1-2.6) and 2.1 (1.7-2.6) years for women, and 2.9 (95% CI: 2.6-3.1), 2.0 (1.2-3.1) and 2.2 (0.5-2.3) for men, respectively. Those living in residential and nursing homes had a shorter survival when aged 90 years, with similar non-significant effects for those aged 95 and 100 years. After the age of 100 years, the high mortality rate and small sample size limited the ability to detect any differences between the different groups. Conclusion: even at the very oldest ages, the majority live in non-institutionalised settings. Among the oldest old, women were frailer than men. Being male and living in residential nursing homes shortened survival in those aged 90 years or more. [ABSTRACT FROM AUTHOR]

Background: Diabetes is common in the older population and is increasing. Glycated hemoglobin (HbA1c) is an indicator of average blood glucose concentration over the past three months. The HbA1c test is currently one of clinical methods used to check diabetes control. Recent studies have suggested diabetes is a risk factor for dementia, cognitive dysfunction and physical disability. In addition, there have reported the relationship between HbA1c and mortality on all cause, cardiovascular disease and cognitive function, but few studies have investigated the relationship concentrating on the older population. The aim of this study is to investigate the association between the level of HbA1c and mortality from all causes, incident cardiovascular disease, cognitive decline and physical disability in people aged 65 and over in England and Wales. Methods: 1139 men and women aged 69 years and over who were participants in a ten year population based ageing multi-centre, longitudinal study who had HbA1c measurements after 5-6 years of follow up. All participants were flagged for death notification including causes at the Office of National Statistics. Information on health including vascular conditions, cognitive status, physical function and dementia were available from the study both before and after the HbA1c measurement. Survival analyses and logistic regression were conducted. Results: Mortality from all causes, cardiovascular and ischaemic heart disease increased with increasing HbA1c. Participants with diagnosed diabetes or who had HbA1c≥ 7% but no self-reported diabetes had increased mortality risk from all causes and cardiovascular diseases. The respondents in the group HbA1c ≥7% who had not been diagnosed with diabetes had a significantly higher risk (odds ratio = 4.8 95% CI: 1.1 to 21.6) of developing dementia. Individuals who had self-reported diabetes but a HbA1c level <7% had mortality and dementia incidence comparable to individuals without diabetes and HbA1c <7%. Conclusion: The findings support previous reports that bio-markers of glucose metabolism are associated with long term outcomes, such as mortality and dementia. [ABSTRACT FROM AUTHOR]

ABSTRACTBackgroundDepression in old age is an important public health problem. The aims of this study were to report the prevalence of depression in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), a community-based, cohort.MethodFollowing screening of 13 004 people aged 65 and over from a population base, a stratified random subsample of 2640 participants received the Geriatric Mental State (GMS) examination and were diagnosed using the Automated Geriatric Examination for Computer-Assisted Taxonomy (AGECAT) algorithm.ResultsThe prevalence of depression was 8?7% [95% confidence interval (CI) 7?3?10?2], increasing to 9?7% if subjects with concurrent dementia were included. Depression was more common in women (10?4%) than men (6?5%) and was associated with functional disability, co-morbid medical disorder, and social deprivation. Prevalence remained high into old age, but after adjustment for other associated factors, it was lower in the older age groups.ConclusionsThe prevalence of depression in the elderly is high and remains high into old age, perhaps due to increased functional disability. [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]

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]

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]

This study explores the potential modifying effect of age and mediation effect of co-morbidity on the association between land use mix, a measure of neighbourhood walkability, and five-year mortality among the 2424 individuals participating in the year-10 follow-up of the Cognitive Function and Ageing Study in England. Postcodes of participants were mapped onto Lower-layer Super Output Areas, a small area level geographical unit in the UK, and linked to Generalised Land Use data. Cox regression models were fitted to investigate the association. For the younger older age group (75-79 years), the effect of high land use mix on an elevated risk of mortality was mediated by co-morbidity. For older old age groups (80-84, 85+ years), a higher land use mix was directly associated with a 10% lower risk of five-year mortality. The findings suggest differential impacts of land use mix on the health of the younger and older old. [ABSTRACT FROM AUTHOR]

Background: Depression is a leading cause of disability, with older people particularly susceptible to poor outcomes., Aims: To investigate whether the prevalence of depression and antidepressant use have changed across two decades in older people., Method: The Cognitive Function and Ageing Studies (CFAS I and CFAS II) are two English population-based cohort studies of older people aged ≥65 years, with baseline measurements for each cohort conducted two decades apart (between 1990 and 1993 and between 2008 and 2011). Depression was assessed by the Geriatric Mental State examination and diagnosed with the Automated Geriatric Examination for Computer-Assisted Taxonomy algorithm., Results: In CFAS I, 7635 people aged ≥65 years were interviewed, of whom 1457 were diagnostically assessed. In CFAS II, 7762 people were interviewed and diagnostically assessed. Age-standardised depression prevalence in CFAS II was 6.8% (95% CI 6.3-7.5%), representing a non-significant decline from CFAS I (risk ratio 0.82, 95% CI 0.64-1.07, P = 0.14). At the time of CFAS II, 10.7% of the population (95% CI 10.0-11.5%) were taking antidepressant medication, more than twice that of CFAS I (risk ratio 2.79, 95% CI 1.96-3.97, P < 0.0001). Among care home residents, depression prevalence was unchanged, but the use of antidepressants increased from 7.4% (95% CI 3.8-13.8%) to 29.2% (95% CI 22.6-36.7%)., Conclusions: A substantial increase in the proportion of the population reporting taking antidepressant medication is seen across two decades for people aged ≥65 years. However there was no evidence for a change in age-specific prevalence of depression.

There is evidence to suggest that social isolation is associated with poor cognitive health, although findings are contradictory. One reason for inconsistency in reported findings may be a lack of consideration of underlying mechanisms that could influence this relationship. Cognitive reserve is a theoretical concept that may account for the role of social isolation and its association with cognitive outcomes in later life. Therefore, we aimed to examine the relationship between social isolation and cognition in later life, and to consider the role of cognitive reserve in this relationship. Baseline and two year follow-up data from the Cognitive Function and Ageing Study-Wales (CFAS-Wales) were analysed. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and cognitive reserve was assessed using a proxy measure of education, occupational complexity, and cognitive activity. Linear regression modelling was used to assess the relationship between social isolation and cognition. To assess the role of cognitive reserve in this relationship, moderation analysis was used to test for interaction effects. After controlling for age, gender, education, and physically limiting health conditions, social isolation was associated with cognitive function at baseline and two year follow-up. Cognitive reserve moderated this association longitudinally. Findings suggest that maintaining a socially active lifestyle in later life may enhance cognitive reserve and benefit cognitive function. This has important implications for interventions that may target social isolation to improve cognitive function., Competing Interests: The authors have declared that no competing interests exist.

Background: death certification data are routinely collected in most developed countries. Coded causes of death are a readily accessible source and have the potential advantage of providing complete follow-up, but with limitations., Objective: to investigate the reliability of using death certificates for surveillance of dementia, the time trend of recording dementia on death certificates and predictive factors of recording of dementia., Subjects: individuals aged 65 and over in six areas across England and Wales were randomly selected for the Medical Research Council Cognitive Function and Ageing Study (CFAS) and CFAS II with mortality follow-up., Methods: prevalence of dementia recorded on death certificates were calculated by year. Reporting of dementia on death certificates compared with the study diagnosis of dementia, with sensitivity, specificity and Cohen's κ were estimated. Multivariable logistic regression models explored the impact of potential factors on the reporting of dementia on the death certificate., Results: the overall unadjusted prevalence of dementia on death certificates rose from 5.3% to 25.9% over the last 26 years. Dementia reported on death certificates was poor with sensitivity 21.0% in earlier cohort CFAS, but it had increased to 45.2% in CFAS II. Dementia was more likely to be recorded on death certificates in individuals with severe dementia, or those living in an institution, yet less likely reported if individuals died in hospital., Conclusion: recording dementia on death certificate has improved significantly in the England and Wales. However, such information is still an underestimate and should be used alongside epidemiological estimations., (© The Author(s) 2018.)

Cerebral white matter lesions (WML) are common in the aging brain and are associated with dementia and depression. They are associated with vascular risk factors and small vessel disease, suggesting an ischemic origin, but recent pathology studies suggest a more complex pathogenesis. Studies using samples from the population-representative Medical Research Council Cognitive Function and Ageing Study neuropathology cohort used post-mortem magnetic resonance imaging to identify WML for further study. Expression of hypoxia-related molecules and other injury and protective cellular pathways in candidate immunohistochemical and gene expression microarray studies support a role for hypoxia/ischemia. However, these approaches also suggest that immune activation, blood-brain barrier dysfunction, altered cell metabolic pathways and glial cell injury contribute to pathogenesis. These abnormalities are not confined to WML, but are also found in apparently normal white matter in brains with lesions, suggesting a field effect of white matter abnormality within which lesions arise. WML are an active pathology with a complex pathogenesis that may potentially offer a number of primary and secondary intervention targets., (© 2014 International Society of Neuropathology.)

Objective: Behavioural and psychological symptoms (BPS) are common in the older population and may be an indication of early dementia. We explored the predictive effect of the presence of BPS on the 2-year progression to dementia in a cognitively impaired population aged 65 years and over without dementia at baseline., Methods: Twelve symptoms were measured in 2024 participants without dementia at baseline as part of a population-based longitudinal study of ageing. The risk of progression to dementia was predicted in those with cognitive impairment for each individual BPS and using a BPS composite score., Results: Wandering and persecution were independently associated with progression to dementia after adjustment for socio-demographic factors, cognitive domains and other BPS. When stratifying by cognitive function, those with low cognition (MMSE 0-18) and 4 or more BPS were more likely to progress to dementia than those without BPS., Conclusions: We have shown that some psychiatric symptoms are associated with increased short-term progression to dementia in those with low cognition. The predictive effect of BPS in dementia progression has implications for risk stratification of those at high risk of progression to dementia, along with memory impairment, other cognitive impairment and health variables., (Copyright © 2012 John Wiley & Sons, Ltd.)

Education and lifestyle factors linked with complex mental activity are thought to affect the progression of cognitive decline. Collectively, these factors can be combined to create a cognitive reserve or cognitive lifestyle score. This study tested the association between cognitive lifestyle score and cognitive change in a population-based cohort of older persons from five sites across England and Wales. Data came from 13,004 participants of the Medical Research Council Cognitive Function and Ageing Study who were aged 65 years and over. Cognition was assessed at multiple waves over 16 years using the Mini-Mental State Examination. Subjects were grouped into four cognitive states (no impairment, slight impairment, moderate impairment, severe impairment) and cognitive lifestyle score was assessed as a composite measure of education, mid-life occupation, and current social engagement. A multi-state model was used to test the effect of cognitive lifestyle score on cognitive transitions. Hazard ratios for cognitive lifestyle score showed significant differences between those in the upper compared to the lower tertile with a more active cognitive lifestyle associating with: a decreased risk of moving from no to slight impairment (0.58, 95% CI (0.45, 0.74)); recovery from a slightly impaired state back to a non-impaired state (2.93 (1.35, 6.38)); but an increased mortality risk from a severely impaired state (1.28 (1.12, 1.45)). An active cognitive lifestyle is associated with a more favorable cognitive trajectory in older persons. Future studies would ideally incorporate neuroradiological and neuropathological data to determine if there is causal evidence for these associations.

Background: Previous investigations of test re-test reliability of the Mini-Mental State Examination (MMSE) have used correlations and statistics such as Cronbach's α to assess consistency. In practice, the MMSE is usually used to group individuals into cognitive states. The reliability of this grouping (state based approach) has not been fully explored., Methods: MMSE data were collected on a subset of 2,275 older participants (≥ 65 years) from the population-based Medical Research Council Cognitive Function and Ageing Study. Two measurements taken approximately two months apart were used to investigate three state-based categorisations. Descriptive statistics were used to determine how many people remained in the same cognitive group or went up or down groups. Weighted logistic regression was used to identify predictive characteristics of those who moved group., Results: The proportion of people who remained in the same MMSE group at screen and follow-up assessment ranged from 58% to 78%. The proportion of individuals who went up one or more groups was roughly equal to the proportion that went down one or more groups; most of the change occurred when measurements were close to the cut-points. There was no consistently significant predictor for changing cognitive group., Conclusion: A state-based approach to analysing the reliability of the MMSE provided similar results to correlation analyses. State-based models of cognitive change or individual trajectory models using raw scores need multiple waves to help overcome natural variation in MMSE scores and to help identify true cognitive change.

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., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

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.

Objectives: Investigate the impact of the changes in eligibility within England and Wales (E&W) for prescription within the UK National Health Service for treatment of Alzheimer's disease (AD)., Methods: A population-based study in England and Wales with 13,004 individuals measured with MMSE at baseline was used to examine the distributions of individuals within eligibility criteria. Information obtained from informants enabled classification of the study defined dementia cases to ICD10 diagnosis of subtype (AD, dementia with vascular risk, both or other)., Results: Fifty six per cent of dementia patients (representing 323,000 individuals in E&W) fall into the new MMSE criteria band. A further 120,000, 20% of dementia patients, are estimated to have disease that is considered too mild for treatment. Further examination of type of dementia showed that those with mixed AD and vascular dementia had similar proportions of dementia cases within the treatable MMSE group as the subgroup with AD alone, though with mixed disease individuals more often score below the lower threshold. There is substantial instability in the eligibility groupings over a short time period., Conclusions: The population impact of new NICE criteria of excluding high MMSE scores is to exclude one in five individuals with AD and a further one in ten of those with a mixed disease. Changing the guidance has almost balanced the loss of treatment for the high MMSE group (13%) with the introduction of treatment for those scoring 10/11 (11%)., ((c) 2009 John Wiley & Sons, Ltd.)

Background: the numbers with dementia are projected to double between 2001 and 2040, in line with continued increases in life expectancy. Projections have failed to account for the impact of changing risk factors on future numbers with dementia or disability., Objective: to estimate the size of the disabled population over the next 20 years and explore the impact of treatments that delay onset of cognitive impairment and associated disability., Methods: a dynamic macro-simulation projection model was used to calculate the numbers of older people with disability to 2026. Transition rates to disability and death conditional on a range of conditions, calculated from the MRC Cognitive Function and Ageing Study, were applied to the 1992 England and Wales population. Scenarios for trends in dementia incidence, risk factors and treatment were devised from a systematic review and applied., Findings: population ageing alone resulted in 39% more older people between 2006 and 2026 and 82% more with disability. A combination of reduced incidence of cognitive impairment and disabling consequences alongside improved survival provided the largest reductions in the disabled population (15,000) and the numbers cognitively impaired (302,000) compared with ageing of the population alone., Interpretation: population ageing alone will increase the disabled older population by over 80% and the numbers cognitively impaired by almost 50% over the next 20 years with serious implications for the provision of care. Research priorities should focus on earlier detection of dementia and its risk factors, thereby allowing earlier and more targeted treatment to alleviate its associated disability.

Background: Low education has an impact on life expectancy and level of cognition, but little is known on its effect on life expectancy with cognitive impairment., Methods: The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) collected population-based longitudinal data on people aged 65 years and older including measures of education and cognitive impairment, using the Mini-Mental State Examination (MMSE), for five geographically diverse areas around England and Wales interviewed between 1991 and 2003. Transitions between health states were calculated using Markov chain methods. Life expectancy in different states of cognitive function as measured by MMSE were further explored for different education groups. The effect of fixed and educationally based cut points for cognitive impairment are investigated., Results: Life expectancy spent with cognitive impairment is fairly constant with increasing age at around 1.4 years in men and 2.5 years in women, though this reflects a large increase in the proportion of life spent with cognitive impairment. The differences seen between education groups for the proportion of total life with cognitive impairment (men 13% and women 22% of life lived for low education vs men 7% and women 12% in high education group) disappear when education-adjusted cut points are used (10% in men and 17% in women at age 65 for all education groups)., Conclusions: The results show that there is a substantial amount of life expectancy with cognitive impairment in both men and women. The impairment burden is just as great for those with high education as the lowest educated group.

Objective: to describe the characteristics and survival of the oldest old in England and Wales., Design: retrospective analysis of the oldest old from a population-based cohort study., Setting: population-based study in England and Wales: two rural and three urban sites., Methods: two types of analyses were conducted: (i) a descriptive analysis of those individuals who were aged 90 years or more, and 100 years or more, and (ii) a survival analysis of those who reached their 90th, 95th, or 100th birthday during the study. Median survival time was calculated by the Kaplan-Meier method. Effects of socio-demographic characteristics on survival were evaluated using the Cox proportional-hazards regression model., Results: in total, 958 individuals aged 90 years or more, and 24 individuals aged 100 years or more, had been interviewed at least once during the study. Twenty-seven per cent were living in residential or nursing homes. Women aged 90 years or more were more likely to be living in residential and nursing homes, be widowed, have any disability or have lower MMSE scores. The centenarians were mostly cognitively and functionally impaired. The median survival times for those reaching their 90th (n = 2,336), 95th (n = 638), or 100th birthday (n = 92) during the study were 3.7 years (95% CI: 3.5-4.0), 2.3 (2.1-2.6) and 2.1 (1.7-2.6) years for women, and 2.9 (95% CI: 2.6- 3.1), 2.0 (1.2-3.1) and 2.2 (0.5-2.3) for men, respectively. Those living in residential and nursing homes had a shorter survival when aged 90 years, with similar non-significant effects for those aged 95 and 100 years. After the age of 100 years, the high mortality rate and small sample size limited the ability to detect any differences between the different groups., Conclusion: even at the very oldest ages, the majority live in non-institutionalised settings. Among the oldest old, women were frailer than men. Being male and living in residential nursing homes shortened survival in those aged 90 years or more.

Background: Few population-based studies have examined the whole range of subthreshold syndromes and disorders of anxiety and depression in older people., Aims: To investigate the co-occurrence of anxiety and depressive syndromes in older people. Associations between these conditions and personal and environmental factors are examined., Method: MRC CFAS included 13,004, age 65 years and above, who completed the initial screening interview. A stratified random subsample of 2,640 participated in the assessment interview where the Geriatric Mental State Examination (GMS) was administered. The AGECAT diagnostic system was used to generate subthreshold and disorder-level of anxiety and depression as well as the combination of these into eight syndromes categories plus a group without any of the syndromes categories. Prevalences, unadjusted and adjusted odds ratios are calculated for the syndrome categories in relation to cross-sectional personal and environmental factors, and odds ratios of subthreshold and disorders level are estimated., Results: The overall prevalence of anxiety and depressive disorders are 3.1% and 9.7% respectively. The overall prevalence of either anxiety or depressive disorder (anxiety disorder with subthreshold depression, mixed anxiety and depressive disorder with subthreshold anxiety) where they overlapped is 8.4%. The highest Odds Ratios unadjusted and adjusted for age and gender, of anxiety and depressive disorders and significant for trend are found for increasing disability. Disability has a strong relationship with all the co-morbid syndrome categories. In all analyses women showed significant higher estimates than men., Conclusions: Our study demonstrated high estimates where anxiety and depression occurred in parallel both as disorders and as subthreshold syndromes.

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) for ages 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 > or =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 planning for patients, carers, service providers, and policy makers.

Objectives: To estimate population norms for use in assessment of individuals in relation to their age-matched peers using true longitudinal patterns of decline., Design: Longitudinal study of 10 years of follow-up data from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) on the most commonly used cognitive test across clinical and research settings., Setting: England and Wales., Participants: Thirteen thousand four people were seen in five sites at baseline, with follow up at 2, 5, and 10 years., Measurements: Mini-Mental State Examination (MMSE) score at three interviews over 10 years. A total of 42,777 MMSE scores were used in the analysis., Results: MMSE norms are presented according to age and split according to sex using longitudinal data. Potential cohort effects and dropout of individuals with low MMSE scores have been accounted for., Conclusion: It is likely that the cognitive MMSE scale will continue to be used in many settings and across the age range. The figures presented here can be used to plot individual performance and chart where there is change in the relative position of one individual compared with others.

Background: Factors associated with the loss of participants in long-term longitudinal studies of ageing, due to refusal or moves, have been discussed less than those with short term follow-up., Methods: In a population-based study of cognition and ageing (the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)), factors associated with dropout due to refusal and moving in the first follow-up period (over two years) are compared with factors associated with dropout over ten years. Participants at 10-year follow-up are compared with their age-standardised baseline contemporaries., Results: Some consistent trends are found over the longer term. Refusers tended to have poorer cognition, less years of education, not have a family history of dementia and be women. Characteristics of people who moved differed between waves, but the oldest and people in worse health moved more. When surviving and responding individuals at ten years are compared with those of the same age at baseline many differences are found. Individuals of lower social class, education, cognitive ability, in residential care, with sight/hearing problems and poor/fair self-reported health are less likely to be seen after 10 years of follow-up. Individuals report more health problems when they participate in multiple interviews., Conclusion: The characteristics of refusers in the longer term are similar to those refusing to participate over the shorter term. Long-term follow-up studies will under represent the disadvantaged and disabled but represent full health status of participating individuals better. There are advantages and disadvantages to both short-term and long-term follow-up.

Background: This paper reports the association between self-reported diseases and impairments and 2-year onset of disability in a prospective study of people aged 65 years or older in five urban and rural centers in England and Wales (Medical Research Council Cognitive Function and Ageing Study; MRC-CFAS)., Methods: We initially reviewed risk factors for onset of disability in 35 prospective studies of functional decline in older people published in 1998-2001. In the present study, disability was defined as requiring help from another person at least several times a week and was assessed by dependency in activities of daily living. Polytomous and bivariate logistic regression models were fitted for onset of disability and mortality among those nondisabled at baseline (n=7913), adjusting for age, sex, and sociodemography., Results: Among prevalent conditions, arthritis (population-attributable risk 11.4%) and cognitive impairment indicated by a Mini-Mental State Examination score of