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BACKGROUND: Recent research suggests that preclinical Alzheimer's disease (AD) in people with Down syndrome (DS) is characterized by changes in personality/behaviour and executive dysfunction that are more prominent than deterioration in episodic memory. This study examines the relationship between executive dysfunction and the clinical and preclinical features of AD in DS. To determine the specificity of this relationship, performance on executive function (EF) measures is contrasted with performance on memory measures. METHODS: One hundred and three people with DS (mean age 49 years, range 36-72) with mild to moderate learning disabilities (LD) took part. Dementia diagnosis was based on the CAMDEX informant interview conducted with each participant's main carer. Reported changes in personality/behaviour and memory were recorded. Participants completed six EF and six memory measures (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). First, performance was compared between those with and without established dementia of Alzheimer's type (DAT), controlling for age and LD severity using ANCOVA. Next, the degree to which informant-reported changes predicted cognitive test performance was examined within the non-DAT group using multiple regression analyses. RESULTS: The DAT group (N=25) showed a consistent pattern of impaired performance relative to the non-DAT group (N=78), across all measures. Within the non-DAT group, number of informant-reported personality/behaviour changes was a significant predictor of performance on two EF and two 'executive memory' tests (but not on episodic memory tests). Informant-reported memory changes, however, were associated with impaired performance on a delayed recall task only. CONCLUSIONS: These findings provide further evidence for a specific impairment in frontal-lobe functioning in the preclinical stages of AD in DS. Implications for the assessment, diagnosis, and management of dementia in DS are discussed. [ABSTRACT FROM AUTHOR]

Background. Common mental disorder prevalence decreases substantially around the conventional retirement age for men in the UK, but trends for older women are more continuous. Prevalence changes in depression and anxiety around retirement are less clear, as is the role of risk factors. The aim of this study was to establish whether work status, age or other known risk factors account for the reduced prevalence of depressive episode and anxiety disorder around retirement ages for men and for women.Method. The British Psychiatric Morbidity Survey (BPMS) 2000 was analysed, including 1875 men and 2253 women aged 45-75 years. Diagnoses were from the Revised Clinical Interview Schedule (CIS-R). Logistic models were adjusted for sociodemographic factors, social network, work status, life events, physical illness and disability.Results. There are marked reductions in the prevalence of depressive episode after 60 years for women [60% lower prevalence, 95% confidence interval (CI) 40-80] and 65 years for men (90% lower prevalence, 95% CI 70-100), compared to the youngest age groups. For anxiety disorder, the reduction in prevalence was 80% (95% CI 60-90) for men and 40% (95% CI 20-60) for women. In fully adjusted multivariate models, the strong association between diagnoses and age groups remained, for both genders. Work status was a significant factor for men but not for women.Conclusion. There is a discontinuity in the prevalence of depressive episode for both men and women, coinciding with statutory retirement ages. No studied risk factor reduced the associations between age group and disorders. This population scale recovery may provide a model for understanding non-genetic factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains. OBJECTIVE: To harmonise the Cambridge Cognitive Examination between seven European countries. METHOD: 40 patients with probable or possible Alzheimer's disease of each of the seven countries were administered the Cambridge Cognitive Examination. The Nurse Observation Scale for Geriatrics was used to assess concordance between cognitive and behavioural measures. RESULTS: Only small differences between the various Cambridge Cognitive Examination versions were found, and patterns of correlation between Cambridge Cognitive Examination and the Nurse Observation Scale for Geriatrics were consistent. CONCLUSION: These findings indicate that the harmonisation of the Cambridge Cognitive Examination was successful. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To study the relationships between global self-rated health, reported physical symptoms and depressive symptoms and the receipt of community services by very elderly people, and to examine changes in these variables over time. DESIGN: Three-wave study with follow-up at 2.4 and 6 years after first interview. Structured interview, incorporating cognitive examination (Mini-Mental State Examination) and enquiring specifically about overall self-rated health, physical symptoms and depressive symptoms. SETTING: Community setting in city of Cambridge, UK. PARTICIPANTS: 2609 were initially recruited: all patients aged 75 years and over from lists of six general practices (and one in three from a seventh practice). At 2.4 years, 1173 individuals re-examined and at 6 years 628 individuals. MEASUREMENTS: General health self-rated in comparison to others of similar age and individual physical and depressive symptoms self-rated as present or absent. Symptoms were added to produce physical health and depressive symptom scores. Data presented from cross-sectional analysis of 6-year sample; also examined longitudinal data from all three waves of study for ageing and cohort effects. Finally the effect of health variables on the receipt of services was examined. Statistics used included chi(2) and non-parametric statistics for continuous data, also odds ratios for likelihood of receiving services. RESULTS: At 6 years, 70% rated their overall health as good or very good. Overall self-rated health showed both ageing and cohort effects, improving with increasing age and especially with more recent cohort. Reported physical symptoms increased with ageing. Depression scores also increased with ageing but the relationship between depressive symptoms and ageing was less clear-cut. Receipt of services was associated with poor self-rated health and reported physical symptoms as well as with ageing. Higher depression scores at 2.4 years were associated with increased service receipt at 6 years, indicating a lag between the symptoms and the service response. Individuals in the more recent cohort were less likely to receive services, but those who did so received more frequent contact. CONCLUSIONS: Although very elderly people have a high prevalence of reported physical symptoms, they often rate their overall health as good. There was a stronger relationship between ageing and physical symptoms than with depressive symptoms. Symptoms of both kinds influenced the likelihood of receiving services, although there was a lag between depressive symptoms and service response. Cohort effects on service receipt may reflect changes in public service policy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: to compare the domiciliary service receipt of cognitively impaired and equally dependent physically impaired elderly women prior to the passing of the UK Community Care Act. METHODS: secondary analysis of a population survey conducted in 1986 in the city of Cambridge. The analysis used data on 1585 women aged 75 and over living in the community. The effect of type of impairment on the receipt of domiciliary services (meals-on-wheels, home help and community nursing) is measured using a multivariate model which allows for adjustment for dependency level and other potential confounding factors. RESULTS: the odds of an elderly woman getting help from any of the domiciliary services whilst not being significantly affected by cognitive impairment (odds ratio 0.7, 95% CI 0.5-1.2) are increased by physical impairment (odds ratio 1.8, 95% CI 1.2-2.5). Similar results were found for the home help service. The differences were exaggerated in the case of the community nursing service, whilst receipt of meals-on-wheels was similar for women of with all types of impairment. CONCLUSIONS: in the late 1980s, cognitively impaired elderly women received less help from the domiciliary services than equally dependent physically frail women who lived in similar household circumstances. The development of specialist services appropriate to the needs of cognitively impaired elderly people presents a challenge to community care policy, especially since this group are at high risk of institutionalization. [ABSTRACT FROM AUTHOR]

Background: Recent trends on measurement of well-being have elevated the scientific standards and rigor associated with approaches for national and international comparisons of well-being. One major theme in this has been the shift toward multidimensional approaches over reliance on traditional metrics such as single measures (e.g. happiness, life satisfaction) or economic proxies (e.g. GDP)., Methods: To produce a cohesive, multidimensional measure of well-being useful for providing meaningful insights for policy, we use data from 2006 and 2012 from the European Social Survey (ESS) to analyze well-being for 21 countries, involving approximately 40,000 individuals for each year. We refer collectively to the items used in the survey as multidimensional psychological well-being (MPWB)., Results: The ten dimensions assessed are used to compute a single value standardized to the population, which supports broad assessment and comparison. It also increases the possibility of exploring individual dimensions of well-being useful for targeting interventions. Insights demonstrate what may be masked when limiting to single dimensions, which can create a failure to identify levers for policy interventions., Conclusions: We conclude that both the composite score and individual dimensions from this approach constitute valuable levels of analyses for exploring appropriate policies to protect and improve well-being.

There is no universally agreed definition of well-being as a subjective experience, but Huppert and So (2013) adopted and systematically applied the definition of well-being as positive mental health-the opposite of the common mental disorders described in standard mental health classifications (e.g., Diagnostic and Statistical Manual of Mental Disorders ). We extended their theoretical approach to include multi-item scales, using 2 waves of nationally representative U.S. adult samples to develop, test, and validate our multidimensional measure of well-being (WB-Pro). This resulted in a good-fitting a priori (48-item, 15-factor) model that was invariant over time, education, gender, and age; showed good reliability (coefficient αs .81-.93), test-retest correlation (.73-.85; M = .80), and convergent/discriminant validity based on a multitrait-multimethod analysis, and relations with demographic variables, selected psychological measures, and other multidimensional and purportedly unidimensional well-being measures. Further, we found that items from 2 widely used, purportedly unidimensional well-being measures loaded on different WB-Pro factors consistent with a priori predictions based on the WB-Pro factor structure, thereby calling into question their claimed unidimensionality and theoretical rationale. Because some applications require a short global measure, we used a machine-learning algorithm to construct 2 global well-being short versions (five- and 15-item forms) and tested these formative measures in relation to the full-form and validity criteria (to download short and long versions see https://ippe.acu.edu.au/research/research-instruments/wb-pro). The WB-Pro appears to be one of the most comprehensive measures of subjective well-being, based on a sound conceptual model and empirical support, with broad applicability for research and practice, as well as providing a framework for evaluating the breadth of other well-being measures. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective: This study aims to investigate the evidence of the efficacy of mindfulness-based stress reduction (MBSR) in improving stress, depression and anxiety in breast cancer patients., Methods: An extensive systematic electronic review (PubMed, Embase, CINAHL, PsyArticles, PsycINFO, Scopus, Ovid, Web of Science and The Cochrane Library) and a hand search were carried out from 15 October 2011 to 30 November 2011 to retrieve relevant articles using 'mindfulness' or 'mindfulness-based stress reduction' and 'breast cancer' as keywords. Information about the baseline characteristics of the participants, interventions and findings on perceived stress, depression and anxiety was extracted from each study., Results: Nine published studies (two randomised controlled trials, one quasi-experimental case-control study and six one-group, pre-intervention and post-intervention studies) up to November 2011 that fulfilled the inclusion criteria were analysed. The pooled effect size (95% CI) for MBSR on stress was 0.710 (0.511-0.909), on depression was 0.575 (0.429-0.722) and on anxiety was 0.733 (0.450-1.017)., Conclusion: On the basis of these findings, MBSR shows a moderate to large positive effect size on the mental health of breast cancer patients and warrants further systematic investigation because it has a potential to make a significant improvement on mental health for women in this group., (Copyright © 2012 John Wiley & Sons, Ltd.)

Cytomegalovirus (CMV) is a common herpesvirus infection and stimulates the expansion of very large numbers of CMV-specific T cells that reduce the CD4/CD8 ratio and suppress the number of naïve T cells. CMV infection has been associated with frailty and impaired survival. We investigated the correlates of CMV and the impact of the CMV infection on mortality within a cohort of 511 individuals aged at least 65 years who were followed up for 18 years. The mean age of the participants was 74 years of which 70% were CMV-seropositive. CMV was strongly linked to socio-economic status, and CMV infection increased the annual mortality rate by 42% (Hazard ratio = 1.42, 95% CI: 1.11-1.76 after adjusting for age, sex and baseline socio-economic and health variables) corresponding to 3.7 years lower life expectancy from age 65. Infection was associated with a near doubling of cardiovascular deaths, whereas there was no increase in mortality from other causes. These results show that CMV infection markedly increases the mortality rate in healthy older individuals due to an excess of vascular deaths. These findings may have significant implications for the study of immune senescence and if confirmed more generally could have important implications for measures to optimize the health of the elderly., (© 2013 John Wiley & Sons Ltd and the Anatomical Society.)

Governments around the world are recognising the importance of measuring subjective well-being as an indicator of progress. But how should well-being be measured? A conceptual framework is offered which equates high well-being with positive mental health. Well-being is seen as lying at the opposite end of a spectrum to the common mental disorders (depression, anxiety). By examining internationally agreed criteria for depression and anxiety (DSM and ICD classifications), and defining the opposite of each symptom, we identify ten features of positive well-being. These combine feeling and functioning, i.e. hedonic and eudaimonic aspects of well-being: competence, emotional stability, engagement, meaning, optimism, positive emotion, positive relationships, resilience, self esteem, and vitality. An operational definition of flourishing is developed, based on psychometric analysis of indicators of these ten features, using data from a representative sample of 43,000 Europeans. Application of this definition to respondents from the 23 countries which participated in the European Social Survey (Round 3) reveals a four-fold difference in flourishing rate, from 41% in Denmark to less than 10% in Slovakia, Russia and Portugal. There are also striking differences in country profiles across the 10 features. These profiles offer fresh insight into cultural differences in well-being, and indicate which features may provide the most promising targets for policies to improve well-being. Comparison with a life satisfaction measure shows that valuable information would be lost if well-being was measured by life satisfaction. Taken together, our findings reinforce the need to measure subjective well-being as a multi-dimensional construct in future surveys.

A key issue in the field of inclusive design is the ability to provide designers with an understanding of people's range of capabilities. Since it is not feasible to assess product interactions with a large sample, this paper assesses a range of proxy measures of design-relevant capabilities. It describes a study that was conducted to identify which measures provide the best prediction of people's abilities to use a range of products. A detailed investigation with 100 respondents aged 50-80 years was undertaken to examine how they manage typical household products. Predictor variables included self-report and performance measures across a variety of capabilities (vision, hearing, dexterity and cognitive function), component activities used in product interactions (e.g. using a remote control, touch screen) and psychological characteristics (e.g. self-efficacy, confidence with using electronic devices). Results showed, as expected, a higher prevalence of visual, hearing, dexterity, cognitive and product interaction difficulties in the 65-80 age group. Regression analyses showed that, in addition to age, performance measures of vision (acuity, contrast sensitivity) and hearing (hearing threshold) and self-report and performance measures of component activities are strong predictors of successful product interactions. These findings will guide the choice of measures to be used in a subsequent national survey of design-relevant capabilities, which will lead to the creation of a capability database. This will be converted into a tool for designers to understand the implications of their design decisions, so that they can design products in a more inclusive way., (Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

BACKGROUND: Little is known about the long-term consequences of positive wellbeing in childhood in the general population. We used the MRC National Survey of Health and Development (the British 1946 birth cohort) to test associations between adolescent positive wellbeing and social functioning in midlife. METHOD: Temperament and behaviour at ages 13 and 15 years were rated by school teachers on a range of criteria. These mostly referred to absence or presence of conduct and emotional problems, but four items allowed positive ratings: 'very popular with other children', 'unusually happy and contented', 'makes friends extremely easily' and 'extremely energetic, never tired'. In addition, at age 16 years survey members self-completed the Maudsley Personality Inventory, from which a summary measure of extraversion was derived, as this was previously found to be associated with midlife positive wellbeing in this cohort. RESULTS: Being a happy child, defined as receiving at least two of the above teacher ratings, was positively associated with midlife functioning and wellbeing, specifically a low probability of lifetime emotional problems, a high frequency of contact with friends or relatives, engagement in social activities, and to a lesser extent feeling satisfied with accomplishments in working life. These associations were independent of father's social class, childhood cognition, educational attainment, and midlife occupational social class. There were no independent associations between being a happy child and educational or occupational attainment, being married, engagement in prosocial activities, taking leadership in community activities, and with life satisfaction in general or with family life. Extraversion was associated with a low probability of lifetime emotional problems, high engagement in social activities, being married, general midlife life satisfaction, and satisfaction with family life, but not with social contact, prosocial activity, leadership activity, or work satisfaction. While childhood conduct and emotional problems were associated with few of the social and life satisfaction outcomes, the former were negatively associated with educational and occupational attainment, and positively with divorce, whereas the latter were negatively associated with being married. CONCLUSIONS: Prospectively rated childhood wellbeing has long-term beneficial links to adult functioning; our results also support the view that positive wellbeing has a unique impact on these outcomes, and does not merely represent the absence of mental ill-health.

Background: Certain parenting styles are influential in the emergence of later mental health problems, but less is known about the relationship between parenting style and later psychological well-being. Our aim was to examine the association between well-being in midlife and parental behaviour during childhood and adolescence, and the role of personality as a possible mediator of this relationship., Method: Data from 984 women in the 1946 British birth cohort study were analysed using structural equation modelling. Psychological well-being was assessed at age 52 years using Ryff's scales of psychological well-being. Parenting practices were recollected at age 43 years using the Parental Bonding Instrument. Extraversion and neuroticism were assessed at age 26 years using the Maudsley Personality Inventory., Results: In this sample, three parenting style factors were identified: care; non-engagement; control. Higher levels of parental care were associated with higher psychological well-being, while higher parental non-engagement or control were associated with lower levels of psychological well-being. The effects of care and non-engagement were largely mediated by the offspring's personality, whereas control had direct effects on psychological well-being. The psychological well-being of adult women was at least as strongly linked to the parenting style of their fathers as to that of their mothers, particularly in relation to the adverse effects of non-engagement and control., Conclusions: This study used a prospective longitudinal design to examine the effects of parenting practices on psychological well-being in midlife. The effects of parenting, both positive and negative, persisted well into mid-adulthood.

The aim of this study is to assess the effective measurement range of Ryff's Psychological Well-being scales (PWB). It applies normal ogive item response theory (IRT) methodology using factor analysis procedures for ordinal data based on a limited information estimation approach. The data come from a sample of 1,179 women participating in a midlife follow-up of a national birth cohort study in the UK. The PWB scales incorporate six dimensions: autonomy, positive relations with others, environmental mastery, personal growth, purpose in life and self-acceptance. Scale information functions were calculated to derive standard errors of measurement for estimated scores on each dimension. Construct variance was distinguished from method variance by inclusion of method factors from item wording (positive versus negative). Our IRT analysis revealed that the PWB measures well-being most accurately in the middle range of the score distribution, i.e. for women with average well-being. Score precision diminished at higher levels of well-being, and low well-being was measured more reliably than high well-being. A second-order well-being factor loaded by four of the dimensions achieved higher measurement precision and greater score accuracy across a wider range than any individual dimension. Future development of well-being scales should be designed to include items that are able to discriminate at high levels of well-being.

Background: Recent research has suggested a specific impairment in frontal-lobe functioning in the preclinical stages of Alzheimer's disease (AD) in people with Down's syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive dysfunction (EDF), disinhibition and apathy), associated in the literature with disruption of different underlying frontal-subcortical circuits, are a) more or less frequently reported than others and b) related to poor performance on tasks involving different cognitive processes., Method: Seventy-eight participants (mean age 47 years, range 36-72) with DS and mild to moderate intellectual disability (based on ICD-10 criteria), without a diagnosis of dementia of Alzheimer's type (DAT) or other psychiatric disorders, were selected from a larger sample of older adults with DS (n = 122). Dementia diagnosis was based on the CAMDEX informant interview, conducted with each participant's main carer. Informant-reported changes in personality/behaviour and memory were recorded. Participants were scored based on symptoms falling into three behavioural domains and completed five executive function (EF) tasks, six memory tasks (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). Multiple regression analyses were conducted to determine the degree to which the behavioural variables of 'EDF', 'disinhibition' and 'apathy', along with informant-reported memory decline and antidepressant medication use, predicted performance on the cognitive tasks (whilst controlling for the effects of age and general intellectual ability)., Results: Strikingly, disinhibited behaviour was reported for 95.7% of participants with one or more behavioural change (n = 47) compared to 57.4% with reported apathy and 36.2% with reported EDF. 'Disinhibition' score significantly predicted performance on three EF tasks (designed to measure planning, response inhibition and working memory) and an object memory task, (also thought to place high demands on working memory), while 'apathy' score significantly predicted performance on two different tasks, those measuring spatial reversal and prospective memory (p < 0.05). Informant reported memory decline was associated only with performance on a delayed recall task while antidepressant medication use was associated with better performance on a working memory task (p < 0.05)., Conclusion: Observed dissociation between performance on cognitive tasks associated with reported apathy and disinhibition is in keeping with proposed differences underlying neural circuitry and supports the involvement of multiple frontal-subcortical circuits in the early stages of DAT in DS. However, the prominence of disinhibition in the behavioural profile (which more closely resembles that of disinhibited subtype of DFT than that of AD in the general population) leads us to postulate that the serotonergically mediated orbitofrontal circuit may be disproportionately affected. A speculative theory is developed regarding the biological basis for observed changes and discussion is focused on how this understanding may aid us in the development of treatments directly targeting underlying abnormalities.

Normal aging brings with it changes in dopaminergic and memory functions. However, little is known about how these 2 changes are related. In this study, we identify a link between dopamine, episodic memory networks, and aging, using pharmacological functional magnetic resonance imaging. Young and older adults received a D2-like agonist (Bromocriptine, 1.25 mg), a D2-like antagonist (Sulpiride, 400 mg), and Placebo, in a double-blind crossover procedure. We observed group differences, during memory encoding, in medial temporal, frontal, and striatal regions and moreover, these regions were differentially sensitive across groups to dopaminergic perturbation. These findings suggest that brain systems underlying memory show age-related changes and that dopaminergic function may be key in understanding these changes. That these changes have behavioral consequences was suggested by the observation that drug modulations were most pronounced in older subjects with poorer recognition memory. Our findings provide direct evidence linking ageing, memory, and dopaminergic change.

Context: Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL)., Objective: We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's alpha and Rasch analysis., Results and Interpretation: Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's alpha 0.95 and Person Separation Index 0.94 (Rasch analysis)., Conclusions: We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

Lewy bodies (LBs) appear in the brains of nondemented individuals and also occur in a range of neurodegenerative disorders, such as dementia with Lewy bodies (DLB) and Parkinson's disease. A number of people with a definite diagnosis of Alzheimer's disease (AD) also exhibit these intraneuronal inclusions in allo- and/or neocortical areas. The latter, referred to as Lewy body variant of AD (LBV), bears a clinical resemblance to AD in terms of age at onset, duration of illness, cognitive impairment, and illness severity. Since the presence of LBs is accompanied by neuronal cytoskeleton changes, it is possible that the latter may influence neuronal connectivity via alterations to the synaptic network. To address this, we examined the expression of synaptic proteins (synaptophysin, syntaxin, SNAP-25, and alpha-synuclein) and two cytoskeletal proteins (tau and MAP2) in the brain tissue of subjects enrolled in a population-based autopsy study (n = 47). They were divided into groups with no memory problems (control group, n = 15), LBV (n = 5), AD devoid of LBs (n = 17), cerebrovascular dementia (n = 3), and mixed dementia (n = 7). The LBV and AD groups had a similar degree of cognitive impairment and neuropathological staging in terms of Braak staging and CERAD score. In comparison with the control group and the dementia groups without LBs, the LBV group had significantly lower levels of syntaxin and SNAP-25 (23%) in the neocortex, and depletion of MAP2 (64%), SNAP-25 (34%), and alpha-synuclein (44%) proteins in the medial temporal lobes. These findings suggest that the t-SNARE complex deficit present in LBV may be associated with the presence of LB-related pathology and may explain the more profound cholinergic loss seen in these patients.

Background: Patients with cancer have relatively high rates of anxiety and distress, adversely affecting their well-being and quality of life. Recent studies indicate that addressing these symptoms could result in better response to cancer treatment. Researchers have found that interventions that focus on increasing mental awareness and the frequency of positive experiences may have a greater impact on reducing psychological morbidity and increasing quality of life than interventions that target relief of psychological symptoms., Aim: To develop and test a brief, easy to use intervention that could improve well-being and quality of life in cancer patients., Methods: We developed a simple well-being intervention that made few demands on patient time and required little training resource. Participants were randomly assigned to an intervention group or a deferred entry group. Measures of anxiety, depression, well-being and quality of life were administered at baseline and at follow-ups., Results: Twenty-two women with metastatic breast cancer and 24 men with metastatic prostate cancer were recruited from oncology clinics. Thirteen women and 14 men completed the study. Both qualitative and quantitative data showed that the intervention was acceptable to users. There was statistically significant improvement in quality of life scores on WHOQOL-BREF post-intervention (p=0.046). Compliance with the intervention was good., Conclusions: This brief well-being intervention appears to be a promising technique for improving quality of life of cancer patients, without making undue demands on staff resources or patient time. If further studies confirm its effectiveness, it could prove to be a cost-effective intervention.

Background: Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries., Methods: Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87% for the HRS vs. 67% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale)., Results: US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment x country interaction)., Conclusion: Despite methodological differences in the administration of the surveys in the two countries, US adults aged >/= 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.

Background: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline in women with Alzheimer's disease (AD) or other dementia syndromes., Objectives: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia., Search Strategy: The Cochrane Dementia and Cognitive Improvement Group Specialized Register, which contains records from many medical databases, The Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO and LILACS were searched on 7 November 2007 using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen* and progesterone*., Selection Criteria: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia., Data Collection and Analysis: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane., Main Results: A total of seven trials including 351 women with AD were analysed. Because different drugs were used at different studies it was not possible to combine more than two studies in any analysis.On a clinical global rating, clinicians scored patients taking CEE as significantly worse compared with the placebo group on the Clinical Dementia Rating scale after 12 months (overall WMD = 0.35, 95% CI = 0.01 to 0.69, z = 1.99, P < 0.05).Patients taking CEE had a worse performance on the delayed recall of the Paragraph Test (overall WMD = -0.45, 95% CI = -0.79 to -0.11, z = 2.60, P < 0.01) after one month than those taking placebo. They had a worse performance on Finger Tapping after 12 months (WMD = -3.90, 95% CI = -7.85 to 0.05, z = 1.93, P < 0.05).Limited positive effects were found for the lower dosage of CEE (0.625 mg/day) which showed a significant improvement in MMSE score only when assessed at two months, and disappeared after correction for multiple testing. No significant effects for MMSE were found at longer end points (3, 6 and 12 months of treatment). With a dosage of 1.25 mg/d CEE, short-term significant effects were found for Trial-Making test B at one month and Digit Span backward at four months. After two months of transdermal diestradiol (E2) treatment, a highly significant effect was observed for the word recall test (WMD = 6.50, 95% CI = 4.04 to 8.96, z = 5.19, P < 0.0001). No other significant effects were found for other outcomes measured., Authors' Conclusions: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD.

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.

Psychological science has usually approached the treatment of disorder through research on individual combinations of risk and protective factors (including life experiences, thinking styles, behaviors, social relationships and genes) and the application of interventions that focus on improvements in the individual. However, we can do better than this. Not only should we be aiming to enhance well-being rather than merely reducing disorder, but we should also be doing so for the majority of people rather than the few who have a disorder. In this article, I focus on the mental health spectrum and make the case for a broad population-based approach. I argue that a very small shift in the population mean of the underlying symptoms or risk factors can do more to enhance well-being and reduce disorder than would any amount of intervention with individuals who need help. Examples from research on alcohol abuse and psychological distress are presented to illustrate the value of a population-based approach., (© 2009 Association for Psychological Science.)

Background: depression is associated with poor cognitive function, though little is known about the relationship between psychological well-being and cognitive function., Objective: to investigate whether psychological well-being is associated with levels of cognitive function., Design: nationally representative population-based cohort study., Setting and Participants: 11,234 non-institutionalised adults aged 50 years and over of the English Longitudinal Study of Ageing in 2002., Methods: psychological well-being was measured using the CASP-19, and cognitive function was assessed using neuropsychological tests of time orientation, immediate and delayed verbal memory, prospective memory, verbal fluency, numerical ability, cognitive speed and attention. The relation of psychological well-being to cognitive function was modelled using linear regression., Results: on a global cognitive score combining all cognitive tests, those in the fifth quintile of psychological well-being scored an average of 0.30 SD units higher than those in the lowest quintile (95% CI 0.24-0.35) after adjustment for depressive symptoms and sociodemographics. This association remained after additional adjustment for physical health and health behaviours. The same pattern of association was observed for men and women, and across all cognitive domains., Conclusions: in a large population of community living adults, higher levels of psychological well-being were associated with better cognitive function.

Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key.

Background: Individual differences in personality influence the occurrence, reporting and outcome of mental health problems across the life course, but little is known about the effects on adult psychological well-being. The aim of this study was to examine long range associations between Eysenck's personality dimensions and psychological well-being in midlife., Methods: The study sample comprised 1,134 women from the 1946 British birth cohort. Extraversion and neuroticism were assessed using the Maudsley Personality Inventory in adolescence (age 16 years) and early adulthood (age 26). Psychological well-being was assessed at age 52 with a 42-item version of Ryff's Psychological Well-being Scale. Analyses were undertaken within a structural equation modelling framework that allowed for an ordinal treatment of well-being and personality items, and latent variable modelling of longitudinal data on emotional adjustment. The contribution of mental health problems in linking personality variations to later well-being was assessed using a summary measure of mental health (emotional adjustment) created from multiple time-point assessments., Results: Women who were more socially outgoing (extravert) reported higher well-being on all dimensions. Neuroticism was associated with lower well-being on all dimensions. The effect of early neuroticism on midlife well-being was almost entirely mediated through emotional adjustment defined in terms of continuities in psychological/ psychiatric distress. The effect of extraversion was not mediated by emotional adjustment, nor attenuated after adjustment for neuroticism., Conclusions: Individual differences in extraversion and neuroticism in early adult life influence levels of well-being reported in midlife.

Background: The relationship between stroke risk and cognitive function has not previously been examined in a large community living sample other than the Framingham cohort. The objective of this study was to examine the relationship between 10-year risk for incident stroke and cognitive function in a large population-based sample., Methods: Participants were 7377 adults aged 50 years and over of the 2002 wave of the English Longitudinal Study of Ageing, a prospective cohort study. A modified version of the Framingham Stroke Risk Profile (incorporating age, sex, systolic blood pressure, antihypertensive medication, diabetes, smoking status, cardiovascular disease, and atrial fibrillation) was used to assess 10-year risk of stroke. Linear regression models were used to determine the cross-sectional relationship of stroke risk to global cognitive function and performance in multiple cognitive domains., Results: In unadjusted models 10 percentage point increments of 10-year stroke risk were associated with poor global cognitive function (-0.40 SD units, 95% CI -0.43 - -0.38), and lowered performance in all cognitive domains. After statistical adjustment for age, sex, testing interval and other correlates of cognitive function the association with stroke risk was attenuated though remained significant for global cognitive function (-0.06 SD units, 95% CI -0.09 - -0.03), immediate and delayed verbal memory, semantic verbal fluency and processing speed., Conclusion: In individuals free from a history of stroke or dementia, high subclinical cerebrovascular disease burden was associated with worse cognitive function in multiple domains.

Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected., Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison's disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue., Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects., Conclusion: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison's disease.

Objectives: To assess the relationship between cognitive function, socioeconomic status, and neighborhood deprivation (lack of local resources of all types, financial and otherwise)., Design: Nationally representative cross-section., Setting: The English Longitudinal Study of Ageing (ELSA)., Participants: Seven thousand one hundred twenty-six community-dwelling individuals aged 52 and older and resident in urban areas., Measurements: Individual cognitive function score and index of multiple deprivation (IMD) at the Super Output Area level, adjusting for health, lifestyle, and sociodemographic confounders. Analyses were conducted separately according to sex and age group (52-69 and > or = 70)., Results: IMD affected cognitive function independent of the effects of education and socioeconomic status. For example, in fully adjusted models, women aged 70 and older had a standardized cognitive function score (z-score) that was 0.20 points (95% confidence interval (CI)=0.01-0.39) lower in the bottom 20% of wealth than the top 20%, 0.44 points (95% CI=0.20-0.69) lower in the least-educated group than in the most educated, and 0.31 points (95% CI 0.15-0.48) lower if resident lived in an area in the bottom 20% of IMD than in the top 20%., Conclusion: In community-based older people in urban neighborhoods, neighborhood deprivation--living in a neighborhood with high levels of deprivation, compared with national levels--is associated with cognitive function independent of individual socioeconomic circumstances. The mechanisms underlying this relationship are unclear and warrant further investigation.

Background: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored., Objectives: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia., Search Strategy: Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults., Selection Criteria: All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review., Data Collection and Analysis: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics., Main Results: There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects., Authors' Conclusions: The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist.Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Background: Projections of health and social care need are highly sensitive to assumptions about cohort trends in health and disability. We use a repeated population-based cross-sectional study from the Cambridgeshire centre of the UK Medical Research Council Cognitive Function and Ageing Study to investigate trends in the health of the young-old UK population, Methods: Non-overlapping cohorts of men and women aged 65-69 years in 1991/2 (n = 689) and 1996/7 (n = 687) were compared on: self-reported diseases and conditions; self-rated health; mobility limitation; disability by logistic regression and four-year survival by Cox Proportional Hazards Regression models, with adjustments for differences in socio-economic and lifestyle factors., Results: Survival was similar between cohorts (HR: 0.91, 95% CI: 0.62 to 1.32). There was a significant increase in the number of conditions reported between cohorts, with more participants reporting 3 or more conditions in the new cohort (14.2% vs. 10.1%). When individual conditions were considered, there was a 10% increase in the reporting of arthritis and a significant increase in the reporting of chronic airways obstruction (OR: 1.36, 95% CI: 1.04 to 1.78)., Conclusion: This study provides evidence of rising levels of ill-health, as measured by the prevalence of self-reported chronic conditions, in the newer cohorts of the young-old. Though changes in diagnosis or reporting of disease cannot, as yet, be excluded, to better understand whether our findings reflect real increases in ill-health, investment should be made into improved population-based databases, linking self-report and objective measures of health and function, and including those in long-term care.

Objectives: To assess whether there is a relationship between smoking and levels of overall quality of life, or with the pleasure domain of quality of life, in lower socio-economic groups (SES)., Study Design: Cohort study involving 9176 individuals aged 50 years and over who participated in the Health Survey for England and were followed up in Wave 1 of the English Longitudinal Study of Ageing in 2002., Methods: We classified smokers as never-smokers, ex-smokers and current smokers, and used household wealth as a marker for socio-economic position. Pleasure was assessed using the pleasure subscale of the CASP-19 instrument, a 19-point measure of quality of life that covers four theoretical domains: control, autonomy, self-realization and pleasure., Results: We found that the odds ratio for experiencing lower than median levels of pleasure for smokers with low SES was 1.42 (95% CI 1.16-1.74), and for all smokers was 1.33 (95% CI 1.17-1.51). The same pattern of associations was found when the outcome was total CASP-19 score or positive GHQ-12 score., Conclusions: We found no evidence to support a claim that smoking is associated with heightened levels of pleasure, either in people with low SES or in the general population. In fact, our results suggest the opposite: that smoking is associated with lower levels of pleasure and poorer overall quality of life. Policy decisions on smoking should consider its potentially harmful effect on quality of life and pleasure as well as on other aspects of health.

Background: There is evidence of a U-shaped association between alcohol consumption and physical health outcomes in older people, such that moderate drinking is associated with better outcomes than abstinence or heavy drinking, but whether moderate drinking in older people is associated with better cognition and mental health than non-drinking has not been explored., Objective: To assess the relationship between drinking and cognitive health in middle-aged and older people., Design: Prospective observational study., Setting/participants: Six thousand and five individuals aged 50 and over who participated in Wave 1 of the English Longitudinal Study of Ageing (ELSA) and who were not problem drinkers. Exposure and outcome variables: we examined cognitive function, subjective well-being, and depressive symptoms, and compared the risks associated with having never drunk alcohol, having quit drinking, and drinking at <1, <2 and >2 drinks per day., Results: For both men and women, better cognition and subjective well-being, and fewer depressive symptoms, were associated with moderate levels of alcohol consumption than with never having drunk any., Conclusions: In middle-aged and older men and women, moderate levels of alcohol consumption are associated with better cognitive health than abstinence.

The General Health Questionnaire is widely used to measure the health status of individuals. Most studies have focused on traditional score values for one or more dimensions of psychopathology. We introduce a new analysis model that is person-centred and uses a latent structure approach to group individuals by a discrete latent variable. Data were drawn from a midlife (age 53) follow up of a national birth cohort study (n = 3035). For both men and women, three groups (latent classes) were sufficient to summarise individuals' reports of recent changes in social functioning. The groups differed in the number and nature of the reported changes. Furthermore, they were shown to differ in terms of: (1) reported general health, (2) in mean scores on the conventional GHQ factors and (3) in several other variables external to the GHQ (happiness in job, ability to express feelings and self-confidence). Latent Class Analysis of positively worded GHQ items defined groups who differ in perceptions of recent positive changes in social functioning. These groups extend the value of individual health profiles afforded by the GHQ by using distinctions between categories in the first and second responses that are usually combined.

Background: Investigations of the structure of psychological well-being items are useful for advancing knowledge of what dimensions define psychological well-being in practice. Ryff has proposed a multidimensional model of psychological well-being and her questionnaire items are widely used but their latent structure and factorial validity remains contentious., Methods: We applied latent variable models for factor analysis of ordinal/categorical data to a 42-item version of Ryff's psychological well-being scales administered to women aged 52 in a UK birth cohort study (n = 1,179). Construct (predictive) validity was examined against a measure of mental health recorded one year later., Results: Inter-factor correlations among four of the first-order psychological well-being constructs were sufficiently high (> 0.80) to warrant a parsimonious representation as a second-order general well-being dimension. Method factors for questions reflecting positive and negative item content, orthogonal to the construct factors and assumed independent of each other, improved model fit by removing nuisance variance. Predictive validity correlations between psychological well-being and a multidimensional measure of psychological distress were dominated by the contribution of environmental mastery, in keeping with earlier findings from cross-sectional studies that have correlated well-being and severity of depression., Conclusion: Our preferred model included a single second-order factor, loaded by four of the six first-order factors, two method factors, and two more distinct first-order factors. Psychological well-being is negatively associated with dimensions of mental health. Further investigation of precision of measurement across the health continuum is required.

Background: Lower limb mobility disabilities are well understood in older people, but the causes in middle age have attracted little attention., Objectives: To estimate the prevalence of mobility disabilities among noninstitutionalized adults in England and to compare the disabling symptoms reported by middle-aged and older people., Design: Cross-sectional data from the 2002 English Longitudinal Study of Ageing (ELSA). Mobility disability was identified by level of reported difficulty walking a quarter mile., Participants: Eleven thousand two hundred sixteen respondents aged 50 years and older living in private households in 2002., Results: The prevalence of difficulty walking a quarter mile increases sharply with age, but even in the middle-aged (50 to 64 years age-group) 18% (95% confidence interval [CI]: 16% to 19%) of men and 19% (95% CI: 17% to 20%) of women reported some degree of difficulty. Of the 16 main symptoms reported as causing mobility disability in middle age, 2 dominated: pain in the leg or the foot (43%; 95% CI: 40% to 46%) and shortness of breath/dyspnea (21%; 95% CI: 18% to 23%). Fatigue or tiredness, and stability problems were cited by only 5% and 6%, respectively. These proportions were slightly different from those in the 65 to 79-year age group: 40%, 23%, 6%, and 8%, respectively., Conclusions: Mobility (walking) disabilities in the middle-aged are relatively common. The symptoms reported as causes in this age group differ little from those reported by older groups, and are dominated by lower limb pain and shortness of breath. More clinical attention paid to disabling symptoms may lead to disability reductions in later life.

The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70-79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance.

Background: Research based on retrospective reports by carers suggests that the presentation of dementia in people with Down's syndrome may differ from that typical of Alzheimer's disease (AD) in the general population, with the earliest changes tending to be in personality or behaviour rather than in memory. This is the first long-term prospective study to test the hypothesis that such changes, which are more typical of dementia of frontal type (DFT) in the general population, mark the preclinical stage of AD in DS., Methods: A previously identified population sample of older people with DS, first assessed in 1994 and followed-up 18 months later, were reassessed after a further 5 years. This study focuses on the 55 individuals who took part in the second follow-up. Dementia diagnosis was made using the modified CAMDEX informant interview and neuropsychological assessment was undertaken using the CAMCOG. Progression in clinical presentation was examined and degree of cognitive decline over time (on the CAMCOG and derived measures of executive function (EF) and memory) was compared across groups based on diagnosis and age: AD, DFT, personality/behaviour changes insufficient for a diagnosis of DFT (PBC), no diagnosis <50 years and no diagnosis 50 + years., Results: Progression was observed from early changes in personality and behaviour to an increase in characteristics associated with frontal lobe dysfunction and/or a deterioration in memory, prior to the development of full AD. Individuals who met criteria for DFT were significantly more likely to progress to a diagnosis of AD over the following 5 years than those who did not and those with PBC were significantly more likely to progress to a more severe diagnosis (DFT or AD) than those without. In the 5 years prior to diagnosis, participants with PBC and DFT had shown a degree of global cognitive decline intermediate between those with no dementia and those with AD. Both these groups had shown a significant decline in EF but not in memory, while the AD group had shown significant decline on both measures, with a significantly greater degree of decline in memory. Older participants without informant reported changes showed a more generalised pattern of decline., Conclusions: These findings confirm that the early presentation of AD in DS is characterized by prominent personality and behaviour changes, associated with executive dysfunction, providing support for the notion that the functions of the frontal lobes may be compromised early in the course of the disease in this population. This has important implications for the diagnosis, treatment and management of dementia in people with DS., (Copyright 2006 John Wiley & Sons, Ltd.)

Background: Despite the MMSE's known flaws, it is still used extensively as both a screening instrument for dementia and a population measure of cognitive ability. The aim of this paper is to provide data on the distribution of MMSE scores in a representative sample from the UK population and to compare it with an extended cognitive assessment (EMSE) which covers a wider range of cognitive domains and provides a wider range of difficulty levels., Methods: The MMSE and the EMSE were administered to over 12,000 participants at the screening stage of the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi-centre population-based study in England and Wales with respondents aged 65 years and older., Results: Normative values on the MMSE and EMSE are presented by age group, sex and level of education. There are very large differences between age groups, with smaller differences seen between the sexes and by level of education. The EMSE extends the scores at the high end of the ability range, but is no better than the MMSE at differentiating between dementia and non-dementia., Conclusion: Population-derived norms are valuable for comparing an individual's score to the score that would be expected among the general population, given the individual's specific demographic characteristics.

Introduction: why do we need a science of well-being?

Well-being: towards an integration of psychology, neurobiology and social science

Background: Dementia because of Alzheimer's disease (AD) commonly affects older adults with Down's syndrome (DS). Methods are needed, with established concurrent and predictive validity, to facilitate the diagnostic assessment of dementia, when it is complicated by pre-existing intellectual disabilities (ID). We report on the reliability and validity of a modified version of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) informant interview, for use when assessing people with DS suspected as having dementia., Methods: As part of a previous epidemiological study of older people with DS, the CAMDEX informant interview was used to determine the prevalence of dementia. The 74 people with DS included at that time (Time 1) had also completed the Cambridge Cognitive Examination (CAMCOG), the neuropsychological assessment from the CAMDEX schedule. Fifty-six were assessed again 6 years later (Time 2). Based on the CAMDEX informant interview, nine of the 74 at Time 1, and 11 of the 56 at Time 2, were found to meet clinical criteria for AD. Forty-one scored above floor on the CAMCOG at Time 1 and were included in the analysis of cognitive decline. Concurrent validity was established by comparing diagnosis at Time 2 with independent evidence of objective decline on cognitive tasks since Time 1. Predictive validity was established by examining how accurately diagnosis at Time 1 predicted both cognitive decline and future diagnosis. Inter-rater reliability was determined by comparing the level of agreement between two raters., Results: CAMDEX-based diagnosis of AD was shown to be consistent with objectively observed cognitive decline (good concurrent validity) and to be a good predictor of future diagnosis. Although numbers are small, some support is also provided for the accuracy with which diagnosis predicts cognitive decline. Inter-rater reliability was good with Kappa > 0.8 for 91% of items and > 0.6 for all items., Conclusions: The use of the modified CAMDEX informant interview enables the structured collection of diagnostic information, so that a valid and a reliable diagnosis of dementia can be made in those with pre-existing ID, using established diagnostic criteria.

Background: Previous studies have reported on the association between white blood cell counts, in particular monocytes, and cardiovascular disease, but have predominantly been conducted on middle-aged men. We examined whether this association is sustained in an elderly population-based sample., Methods: Two samples of individuals aged 65 years and older living in Cambridge and Nottingham were recruited from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Venepuncture was undertaken in 1046 individuals, excluding only those who had probable dementia or were physically frail. Monocyte, neutrophil, lymphocyte, eosinophil and basophil counts were analysed for possible associations with history of cardiovascular disease., Results: We found that monocyte and neutrophil counts were both significantly associated with history of cardiovascular disease, with respective odds ratios of 1.48 (95% CI 1.22-1.79) and of 1.44 (95% CI 1.19-1.75) per count tertile. These relationships remained significant on adjusting for age, sex, smoking and body mass index. We found no evidence of association between lymphocyte, eosinophil or basophil counts and history of cardiovascular disease., Conclusions: Monocyte and neutrophil counts are both associated with cardiovascular disease in a relatively healthy elderly population.

Background: CAMCOG is a widely used brief neuropsychological test. To date no normative values are available for English speaking individuals representative of the general population., Objectives: The aims of the study were to describe the population distribution of performance on CAMCOG, and to provide normative data derived from a representative population sample., Methods: CAMCOG was administered at the assessment stage of the MRC Cognitive Function and Ageing Study. MRC CFAS is a multi-centre population-based study in England and Wales in respondents aged 65 years and older. Initial screening provided provisional identification of cognitive impairment. The subsequent assessment interview provided an algorithmic diagnosis of dementia, or other disorders, in a 20% sub-sample., Results: There were large differences between demented and non-demented groups on the CAMCOG total score and on all CAMCOG subscales. Charts of normative values for CAMCOG are presented by age group, sex and education for the non-demented population (n = 1 914, representing 11 008 individuals screened)., Conclusions: Population-derived normative data are valuable for comparing an individual's score to the score which would be expected of the general population, given the individual's specific demographic characteristics., (Copyright 2003 John Wiley & Sons, Ltd.)