Progress in dementia research has been limited, with substantial gaps in our knowledge of targets for prevention, mechanisms for disease progression, and disease-modifying treatments. The growing availability of multimodal datasets opens possibilities for the application of machine learning and artificial intelligence (AI) to help answer key questions in the field. We provide an overview of the state of the science, highlighting current challenges and opportunities for utilisation of AI approaches to move the field forward in the areas of genetics, experimental medicine, drug discovery and trials optimisation, imaging, and prevention. Machine learning methods can enhance results of genetic studies, help determine biological effects and facilitate the identification of drug targets based on genetic and transcriptomic information. The use of unsupervised learning for understanding disease mechanisms for drug discovery is promising, while analysis of multimodal datasets to characterise and quantify disease severity and subtype are also beginning to contribute to optimisation of clinical trial recruitment. Data-driven experimental medicine is needed to analyse data across modalities and develop novel algorithms to translate insights from animal models to human disease biology. AI methods in neuroimaging outperform traditional approaches for diagnostic classification and although challenges around validation and translation remain, there is optimism for their meaningful integration to clinical practice in the near future. AI-based models can also clarify our understanding of the causality and commonality of dementia risk factors, informing and improving risk prediction models along with the development of preventative interventions. The complexity and heterogeneity of dementia requires an alternative approach beyond traditional design and analytical approaches. Although not yet widely used in dementia research, machine learning and AI have the potential to unlock current challenges and advance precision dementia medicine.

BACKGROUND: Observational studies have found an association between attention-deficit/hyperactivity disorder (ADHD) and ischemic stroke. AIMS: the purpose of this study was to investigate whether genetic liability to ADHD has a causal effect on ischemic stroke and its subtypes. METHODS: in this two-sample Mendelian randomization (MR) study, genetic variants (nine single-nucleotide polymorphisms; P 

BACKGROUND: the identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

ImportanceSeveral ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA).ObjectiveTo perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease.Data SourcesMEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched.Study SelectionSystematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk of Bias in Systematic reviews tool was used to assess review quality.Main Outcomes and MeasuresThe prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference.ResultsFrom the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88).Conclusions and RelevanceThis umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.

BACKGROUND: Individual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes. METHODS: We examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006-10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics. FINDINGS: the dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39-9·08, p

Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. Five hundred and thirty-seven patients were visited by mobile teams of doctors and nurses from the National Health Service National Prion Clinic within 5 days of notification of a suspected diagnosis of sporadic Creutzfeldt-Jakob disease, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100-day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. Two hundred and eighty (52.1%) patients were female and the median age was 67.2 (interquartile range 10.5) years. Median survival from initial assessment was 24 days (range 0-1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; Medical Research Council Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical disease phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for methionine homozygous compared with methionine-valine heterozygous; 95% confidence interval 3.02-14.68 for 30-day mortality). of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation, respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sporadic Creutzfeldt-Jakob disease patients using clinical, imaging and genetic data routinely available in a specialist national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care.

OBJECTIVE: to optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics. METHODS: We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data. RESULTS: the analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28). CONCLUSION: Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

BACKGROUND: Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. OBJECTIVES: We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. METHODS: We conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37-73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression. RESULTS: There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup -1.42, 95% CI -1.89, -0.94), grey matter (β -0.91, 95% CI -1.20, -0.62), white matter (β -0.51, 95% CI -0.83, -0.19) and hippocampal volumes (β -0.01, 95% CI -0.02, -0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β -0.01, 95% CI -0.07, 0.05). The association between coffee consumption and dementia was non-linear (Pnon-linearity = 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1-2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). CONCLUSION: High coffee consumption was associated with smaller total brain volumes and increased odds of dementia.

Abstract
. Approximately two-thirds of hospital admissions are older adults and almost half of these are likely to have some form of dementia. People with dementia are not only at an increased risk of adverse outcomes once admitted, but the unfamiliar environment and routinised practices of the wards and acute care can be particularly challenging for them, heightening their confusion, agitation and distress further impacting the ability to optimise their care. It is well established that a person-centred care approach helps alleviate some of the unfamiliar stress but how to embed this in the acute-care setting remains a challenge. In this article, we highlight the challenges that have been recognised in this area and put forward a set of evidence-based ‘pointers for service change’ to help organisations in the delivery of person-centred care. The DEMENTIA CARE pointers cover areas of: dementia awareness and understanding, education and training, modelling of person-centred care by clinical leaders, adapting the environment, teamwork (not being alone), taking the time to ‘get to know’, information sharing, access to necessary resources, communication, involving family (ask family), raising the profile of dementia care, and engaging volunteers. The pointers extend previous guidance, by recognising the importance of ward cultures that prioritise dementia care and institutional support that actively seeks to raise the profile of dementia care. The pointers provide a range of simple to more complex actions or areas for hospitals to help implement person-centred care approaches; however, embedding them within the organisational cultures of hospitals is the next challenge.

GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed PAGEANT (Personal Access to Genome & Analysis of Natural Traits), usable through Graphical User Interface or command line-based version, aiming to serve as a protocol and prototype that guides the overarching design of genetic reporting tools. PAGEANT is structured across five core modules, summarized by five Qs: (i) quality assurance of the genetic data; (ii) qualitative assessment of genetic characteristics; (iii) quantitative assessment of health risk susceptibility based on polygenic risk scores and population reference; (iv) query of third-party variant databases (e.g. ClinVAR and PharmGKB) and (v) quick Response code of genetic variants of interest. Literature review was conducted to compare PAGEANT with academic and industry tools. For 2504 genomes made publicly available through the 1000 Genomes Project, we derived their genomic characteristics for a suite of qualitative and quantitative traits. One exemplary trait is susceptibility to COVID-19, based on the most up-to-date scientific findings reported.

BACKGROUND: Higher vitamin D status has been suggested to have beneficial effects on the brain. OBJECTIVES: to investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke. METHODS: We used prospective data from the UK Biobank (37-73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, center, and socioeconomic, lifestyle, sun behavior, and illness-related factors. Nonlinear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2399 and 3760 cases, respectively). RESULTS: Associations between 25(OH)D and total, gray matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P-nonlinear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10 nmol/L 25(OH)D; adjusted β: -6.1; 95% CI: -11.5, -7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D

We evaluated whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (excluding the APOE region). We included 193,198 UK Biobank participants aged 60-73 years without dementia at baseline. of non-APOE-ε4 carriers, 0.89% (95% CI 0.73-1.08%) current smokers developed dementia compared with 0.49% (95% CI 0.44-0.55%) of never smokers (adjusted HR 1.78; 95% CI 1.39-2.29). In contrast, of one APOE-ε4 allele carriers, 1.69% (95% CI 1.31-2.12%) current smokers developed dementia compared with 1.40% (95% CI 1.25-1.55%) of never smokers (adjusted HR 1.06; 95% CI 0.77-1.45); of two APOE-ε4 alleles carriers, 4.90% (95% CI 2.92-7.61%) current smokers developed dementia compared with 3.87% (95% CI 3.11-4.74%) of never smokers (adjusted HR 0.94; 95% CI 0.49-1.79). of participants with high polygenic risk, 1.77% (95% CI 1.35-2.27%) current smokers developed dementia compared with 1.05% (95% CI 0.91-1.21%) of never smokers (adjusted HR 1.63; 95% CI 1.16-2.28). A significant interaction was found between APOE genotype and smoking status (P = 0.002) while no significant interaction was identified between polygenic risk and smoking status (P = 0.25). APOE genotype but not polygenic risk modified the effect of smoking on dementia risk.

The traditional Mediterranean diet (MedDiet), rich in minimally processed plant foods and fish, has been widely recognized to be one of the healthiest diets. Data from multiple randomized clinical trials have demonstrated its powerful effect against oxidative stress, inflammation and the development and progression of cardiovascular disease, type 2 diabetes, and other metabolic conditions that play a crucial role in the pathogenesis of neurodegenerative diseases. The protecting effects of the MedDiet against cognitive decline have been investigated in several observational and experimental studies. Data from observational studies suggest that the MedDiet may represent an effective dietary strategy for the early prevention of dementia, although these findings require further substantiation in clinical trials which have so far produced inconclusive results. Moreover, as we discuss in this review, accumulating data emphasizes the importance of: 1) maintaining an optimal nutritional and metabolic status for the promotion of healthy cognitive aging, and 2) implementing cognition-sparing dietary and lifestyle interventions during early time-sensitive windows before the pathological cascades turn into an irreversible state. In summary, components of the MedDiet pattern, such as essential fatty acids, polyphenols and vitamins, have been associated with reduced oxidative stress and the current evidence from observational studies seems to assign to the MedDiet a beneficial role in promoting brain health; however, results from clinical trials have been inconsistent. While we advocate for longitudinal analyses and for larger and longer clinical trials to be conducted, we assert our interim support to the use of the MedDiet as a protective dietary intervention for cognitive function based on its proven cardiovascular and metabolic benefits.

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.

IMPORTANCE: Machine learning algorithms could be used as the basis for clinical decision-making aids to enhance clinical practice. OBJECTIVE: to assess the ability of machine learning algorithms to predict dementia incidence within 2 years compared with existing models and determine the optimal analytic approach and number of variables required. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used data from a prospective cohort of 15 307 participants without dementia at baseline to perform a secondary analysis of factors that could be used to predict dementia incidence. Participants attended National Alzheimer Coordinating Center memory clinics across the United States between 2005 and 2015. Analyses were conducted from March to May 2021. EXPOSURES: 258 variables spanning domains of dementia-related clinical measures and risk factors. MAIN OUTCOMES AND MEASURES: the main outcome was incident all-cause dementia diagnosed within 2 years of baseline assessment. RESULTS: in a sample of 15 307 participants (mean [SD] age, 72.3 [9.8] years; 9129 [60%] women and 6178 [40%] men) without dementia at baseline, 1568 (10%) received a diagnosis of dementia within 2 years of their initial assessment. Compared with 2 existing models for dementia risk prediction (ie, Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score, and the Brief Dementia Screening Indicator), machine learning algorithms were superior in predicting incident all-cause dementia within 2 years. The gradient-boosted trees algorithm had a mean (SD) overall accuracy of 92% (1%), sensitivity of 0.45 (0.05), specificity of 0.97 (0.01), and area under the curve of 0.92 (0.01) using all 258 variables. Analysis of variable importance showed that only 6 variables were required for machine learning algorithms to achieve an accuracy of 91% and area under the curve of at least 0.89. Machine learning algorithms also identified up to 84% of participants who received an initial dementia diagnosis that was subsequently reversed to mild cognitive impairment or cognitively unimpaired, suggesting possible misdiagnosis. CONCLUSIONS AND RELEVANCE: These findings suggest that machine learning algorithms could accurately predict incident dementia within 2 years in patients receiving care at memory clinics using only 6 variables. These findings could be used to inform the development and validation of decision-making aids in memory clinics.

BACKGROUND: an increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. METHODS: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. RESULTS: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. CONCLUSIONS: the small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer’s disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5–30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.

. Background
. Being in hospital can be particularly confusing and challenging not only for people living with dementia, but also for their carers and the staff who care for them. Improving the experience of care for people living with dementia in hospital has been recognised as a priority.
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. Objectives
. To understand the experience of care in hospital for people living with dementia, their carers and the staff who care for them and to assess what we know about improving the experience of care.
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. Review methods
. We undertook three systematic reviews: (1) the experience of care in hospital, (2) the experience of interventions to improve care in hospital and (3) the effectiveness and cost-effectiveness of interventions to improve the experience of care. Reviews 1 and 2 sought primary qualitative studies and were analysed using meta-ethnography. Review 3 sought comparative studies and economic evaluations of interventions to improve experience of care. An interweaving approach to overarching synthesis was used to integrate the findings across the reviews.
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. Data sources
. Sixteen electronic databases were searched. Forwards and backwards citation chasing, author contact and grey literature searches were undertaken. Screening of title and abstracts and full texts was performed by two reviewers independently. A quality appraisal of all included studies was undertaken.
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. Results
. Sixty-three studies (reported in 82 papers) were included in review 1, 14 studies (reported in 16 papers) were included in review 2, and 25 studies (reported in 26 papers) were included in review 3. A synthesis of review 1 studies found that when staff were delivering more person-centred care, people living with dementia, carers and staff all experienced this as better care. The line of argument, which represents the conceptual findings as a whole, was that ‘a change of hospital culture is needed before person-centred care can become routine’. From reviews 2 and 3, there was some evidence of improvements in experience of care from activities, staff training, added capacity and inclusion of carers. In consultation with internal and external stakeholders, the findings from the three reviews and overarching synthesis were developed into 12 DEMENTIA CARE pointers for service change: key institutional and environmental practices and processes that could help improve experience of care for people living with dementia in hospital.
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. Limitations
. Few of the studies explored experience from the perspectives of people living with dementia. The measurement of experience of care across the studies was not consistent. Methodological variability and the small number of intervention studies limited the ability to draw conclusions on effectiveness.
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. Conclusions
. The evidence suggests that, to improve the experience of care in hospital for people living with dementia, a transformation of organisational and ward cultures is needed that supports person-centred care and values the status of dementia care. Changes need to cut across hierarchies and training systems to facilitate working patterns and interactions that enable both physical and emotional care of people living with dementia in hospital. Future research needs to identify how such changes can be implemented, and how they can be maintained in the long term. To do this, well-designed controlled studies with improved reporting of methods and intervention details to elevate the quality of available evidence and facilitate comparisons across different interventions are required.
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. Study registration
. This study is registered as PROSPERO CRD42018086013.
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. Funding
. This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 43. See the NIHR Journals Library website for further project information. Additional funding was provided by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.
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Objective: Vitamin D is involved in brain health and function. Our objective was to determine whether the serum 25-hydroxyvitamin D (25OHD) concentration was associated with delirium in a case-control study of geriatric inpatients. Methods: Sixty cases with delirium (mean ± SD, 84.8 ± 5.7years; 58.3% female) and 180 age- and gender-matched controls were enrolled in a geriatric acute care unit between 2012 and 2014. The diagnosis of delirium was made using the Confusion Assessment Method. Hypovitaminosis D was defined using consecutively the consensual threshold value of 50 nmol/L and a threshold value calculated from a sensitivity-specificity analysis. Age, gender, number of acute diseases, use of psychoactive drugs, season of testing, and serum concentrations of calcium, parathyroid hormone, creatinine, albumin, TSH, vitamin B9 and vitamin B12 were used as potential confounders. Results: the 60 cases with delirium exhibited lower 25OHD concentration than 180 matched controls (35.4 ± 30.0 nmol/L vs. 45.9 ± 34.5 nmol/L, p = 0.035). Increased 25OHD concentration was associated with a decrease in delirium prevalence (OR = 0.99 [95CI: 0.98–0.99] per nmol/L of 25OHD, p = 0.038). The concentration distinguishing between cases and controls with the best sensitivity-specificity was found between 29.5 and 30.5 nmol/L. The regression models showed that delirium was associated with hypovitaminosis D defined either as 25OHD ≤ 50 nmol/L (OR = 2.37 [95CI: 1.07–5.25], p = 0.034) or as 25OHD ≤ 30 nmol/L (OR = 2.66 [95 CI: 1.30–5.45], p = 0.008). Conclusions: Decreased serum 25OHD concentrations were associated with delirium among acute geriatric inpatients. The threshold concentration to differentiate between cases and controls was around 30 nmol/L.

Older adults often complain about their memory ability, but it is not clear to what extent subjective memory complaints accurately reflect objective cognitive dysfunctions. The concordance between objective and subjective cognitive performance may be affected by depressive symptoms and by declining insight into cognitive deficits. This study aims to examine longitudinal associations between subjective memory complaints, objective cognitive performance and depressive symptoms. 11,092 participants aged 50 years and above from the English Longitudinal Study of Ageing were followed-up every 2 years over a 6-year period. Two processes latent growth curve models (LGCM) examined associations between levels and changes in several cognitive abilities and subjective memory complaints, unadjusted for depression symptoms. Then three processes LGCM examined associations between levels and changes in depressive symptoms, subjective memory complaints and objective cognitive abilities in the overall sample, and separately among persons with mild cognitive impairment at baseline. More subjective memory complaints were associated with poorer performance in all cognitive domains at baseline. Steeper decline in immediate recall, verbal fluency and processing speed performance was associated increasing subjective memory complaints both in the overall sample and among persons with mild cognitive impairment. Increasing depressive symptoms were associated with both objective and subjective cognitive decline in the overall sample, and only with subjective memory decline among cognitively impaired persons. Self-reported memory complaints may have the potential to identify decline in objective cognitive performance that cannot be explained by depressive symptoms. Among cognitively impaired persons depressive symptoms may amplify subjective but not objective cognitive decline.

IMPORTANCE: Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. OBJECTIVE: to investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS: a retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES: a polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES: Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS: a total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). CONCLUSIONS AND RELEVANCE: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

The 16-item Vitamin D Status Diagnosticator (VDSD) tool was built to diagnose, without resorting to a blood test, hypovitaminosis D among healthy seniors living at home. The objective of this study was to determine the feasibility of the VDSD by general practitioners (GPs), the acceptability to outpatients, and the diagnostic accuracy of the VDSD in primary care. Ten French GPs were asked from March to May 2015 to perform the VDSD in 30 consecutive outpatients aged ≥70years, living at home, presenting with a history of recurrent falls and/or osteomalacia, and taking no vitamin D supplements. Feasibility was defined as a proportion >70% of VDSD forms fully completed. Completing time, acceptance rate and, when applicable, the reasons for non-completing were assessed, together with the metrological properties of the VDSD to identify hypovitaminosis D ≤75nmol/L, or ≤50nmol/L or ≤25nmol/L. of the 242 enrolled patients, 218 (mean, 79 ± 6years; 46.3% women) received a VDSD, i.e. completing rate of 90.1%, with an average completing time of 1 min and 48s. The acceptance rate by the patients was 98.8%, and all GPs were satisfied with the tool. The VDSD identified hypovitaminosis D≤75nmol/L with an accuracy of 84.7%, hypovitaminosis D≤50nmol/L with accuracy 75.4%, and hypovitaminosis D≤25nmol/L with accuracy 71.0% (n = 183 assays). The 16-item VDSD can be considered as feasible, acceptable and accurate for diagnosing hypovitaminosis D among older outpatients in primary care without resorting to an expensive blood test.

BACKGROUND: Apolipoprotein E (APOE) genotype affects the risk of Alzheimer's disease (AD) with inconclusive evidence on the opportunity to mitigate related adverse effects by lifestyle changes. OBJECTIVE: to examine the individual and interactive associations of APOE and objectively-measured physical activity (PA) and sedentary activity with cognitive decline. METHODS: We used data from middle-aged and older UK Biobank participants with repeat tests on visuospatial memory (n = 52,767) and fluid intelligence (n = 19,713), and who also took part in the accelerometer sub-study. PA and sedentary activity were assessed by a wrist-worn accelerometer over a seven-day period. Cognitive decline was defined as >1 standard deviation (SD) reduction in memory or fluid intelligence score, and the mean follow up from baseline was 5.8 years. RESULTS: There was an age dependent association between APOEɛ4 genotype and memory decline (page-interaction = 0.01), with the association only seen in participants who were >65 years (OR 1.33, 95% CI 1.11 to 1.24; for

BACKGROUND: Brief cognitive assessments can result in false-positive and false-negative dementia misclassification. We aimed to identify predictors of misclassification by 3 brief cognitive assessments; the Mini-Mental State Examination (MMSE), Memory Impairment Screen (MIS) and animal naming (AN). METHODS: Participants were 824 older adults in the population-based US Aging, Demographics and Memory Study with adjudicated dementia diagnosis (DSM-III-R and DSM-IV criteria) as the reference standard. Predictors of false-negative, false-positive and overall misclassification by the MMSE (cut-point

Objectives: Poor social connections may be associated with poor cognition in older people who are not experiencing mental health problems, and the trajectory of this association may be moderated by cognitive reserve. However, it is unclear whether this relationship is the same for older people with symptoms of depression and anxiety. This paper aims to explore social relationships and cognitive function in older people with depression and anxiety. Method: Baseline and two-year follow-up data were analysed from the Cognitive Function and Ageing Study–Wales (CFAS-Wales). We compared levels of social isolation, loneliness, social contact, cognitive function, and cognitive reserve at baseline amongst older people with and without depression or anxiety. Linear regression was used to assess the relationship between isolation and cognition at baseline and two-year follow-up in a subgroup of older people meeting pre-defined criteria for depression or anxiety. A moderation analysis tested for the moderating effect of cognitive reserve. Results: Older people with depression or anxiety perceived themselves as more isolated and lonely than those without depression or anxiety, despite having an equivalent level of social contact with friends and family. In people with depression or anxiety, social isolation was associated with poor cognitive function at baseline, but not with cognitive change at two-year follow-up. Cognitive reserve did not moderate this association. Conclusion: Social isolation was associated with poor cognitive function at baseline, but not two-year follow-up. This may be attributed to a reduction in mood-related symptoms at follow-up, linked to improved cognitive function.

OBJECTIVE: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits. METHODS: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of β-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p < 5 × 10). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases. RESULTS: the SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes). CONCLUSIONS: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci.

Earlier diagnosis of dementia is increasingly being recognized as a public health priority. As screening is not generally recommended, case-finding in clinical practice is encouraged as an alternative dementia identification strategy. The approaches of screening and case-finding are often confused, with uncertainty about what case-finding should involve and under what circumstances it is appropriate. We propose a formal definition of dementia case-finding with a clear distinction from screening. We critically examine case-finding policy and practice and propose evidence requirements for implementation in clinical practice. Finally, we present a case-finding pathway and discuss the available evidence for best practice at each stage, with recommendations for research and practice. In conclusion, dementia case-finding is a promising strategy but currently not appropriate due to the substantial gaps in the evidence base for several components of this approach.

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; β = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

IMPORTANCE: Lower educational attainment is associated with a higher risk of dementia. However, less clear is the extent to which other socioeconomic markers contribute to dementia risk. OBJECTIVE: to examine the relationship of education, wealth, and area-based deprivation with the incidence of dementia over the last decade in England and investigate differences between people born in different periods. DESIGN, SETTING, AND PARTICIPANTS: Data from the English Longitudinal Study of Ageing, a prospective cohort study that is representative of the English population, were used to investigate the associations between markers of socioeconomic status (wealth quintiles and the index of multiple deprivation) and dementia incidence. To investigate outcomes associated with age cohorts, 2 independent groups were derived using a median split (born between 1902-1925 and 1926-1943). MAIN OUTCOMES AND MEASURES: Dementia as determined by physician diagnosis and the Informant Questionnaire on Cognitive Decline in the Elderly. RESULTS: a total of 6220 individuals aged 65 years and older enrolled in the study (median [interquartile range] age at baseline, 73.2 [68.1-78.3] years; 3410 [54.8%] female). of these, 463 individuals (7.4%) had new cases of dementia ascertained in the 12 years between 2002-2003 and 2014-2015. In the cohort born between 1926 and 1943, the hazard of developing dementia was 1.68 times higher (hazard ratio [HR] = 1.68 [95% CI, 1.05-2.86]) for those in the lowest wealth quintile compared with those in the highest quintile, independent of education, index of multiple deprivation, and health indicators. Higher hazards were also observed for those in the second-highest quintile of index of multiple deprivation (HR = 1.62 [95% CI, 1.06-2.46]) compared with those in the lowest (least deprived) quintile. CONCLUSIONS AND RELEVANCE: in an English nationally representative sample, the incidence of dementia appeared to be socioeconomically patterned primarily by the level of wealth. This association was somewhat stronger for participants born in later years.

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.

Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers. We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49-1.92; P <. 00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90-2.50; P <. 00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke. Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: to systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. METHODS: We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality. RESULTS: We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer's disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects. CONCLUSIONS: Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.

Objectives: Health and social care services are increasingly reliant on informal caregivers to provide long-term support to stroke survivors. However, caregiving is associated with elevated levels of depression and anxiety in the caregiver that may also negatively impact stroke survivor recovery. This qualitative study aims to understand the specific difficulties experienced by caregivers experiencing elevated symptoms of anxiety and depression. Methods: Nineteen semi-structured interviews were conducted with caregivers experiencing elevated levels of depression and anxiety, with a thematic analysis approach adopted for analysis. Results: Analysis revealed three main themes: Difficulties adapting to the caring role; Uncertainty; and Lack of support. Conclusions: Caregivers experienced significant difficulties adapting to changes and losses associated with becoming a caregiver, such as giving up roles and goals of importance and value. Such difficulties persisted into the long-term and were coupled with feelings of hopelessness and worry. Difficulties were further exacerbated by social isolation, lack of information and poor long-term health and social care support. Clinical Implications: a greater understanding of difficulties experienced by depressed and anxious caregivers may inform the development of psychological support targeting difficulties unique to the caring role. Improving caregiver mental health may also result in health benefits for stroke survivors themselves.

BACKGROUND: the genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: the SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p =. 02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

Introduction: the association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear. Methods: We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia. Results: in the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD. Discussion: Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

Background: Vitamin E occurs naturally in the diet. It has several biological activities, including functioning as an antioxidant to scavenge toxic free radicals. Evidence that free radicals may contribute to the pathological processes behind cognitive impairment has led to interest in the use of vitamin E supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease (AD). This is an update of a Cochrane Review first published in 2000, and previously updated in 2006 and 2012. Objectives: to assess the efficacy of vitamin E in the treatment of MCI and dementia due to AD. Search methods: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources on 22 April 2016 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol. Selection criteria: We included all double-blind, randomised trials in which treatment with any dose of vitamin E was compared with placebo in people with AD or MCI. Data collection and analysis: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. Where appropriate we attempted to contact authors to obtain missing information. Main results: Four trials met the inclusion criteria, but we could only extract outcome data in accordance with our protocol from two trials, one in an AD population (n = 304) and one in an MCI population (n = 516). Both trials had an overall low to unclear risk of bias. It was not possible to pool data across studies owing to a lack of comparable outcome measures. In people with AD, we found no evidence of any clinically important effect of vitamin E on cognition, measured with change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to 0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no evidence of a difference between vitamin E and placebo groups in the risk of experiencing at least one serious adverse event over six to 48 months (risk ratio (RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1 study, n = 304; moderate quality evidence). People with AD receiving vitamin E showed less functional decline on the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory than people receiving placebo at six to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study, n = 280; moderate quality evidence). There was no evidence of any clinically important effect on neuropsychiatric symptoms measured with the Neuropsychiatric Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate quality evidence). We found no evidence that vitamin E affected the probability of progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95% CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five deaths occurred in each of the vitamin E and placebo groups over the 36 months (RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality evidence). We were unable to extract data in accordance with the review protocol for other outcomes. However, the study authors found no evidence that vitamin E differed from placebo in its effect on cognitive function, global severity or activities of daily living There was also no evidence of a difference between groups in the more commonly reported adverse events. Authors' conclusions: We found no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD. Vitamin E was not associated with an increased risk of serious adverse events or mortality in the trials in this review. These conclusions have changed since the previous update, however they are still based on small numbers of trials and participants and further research is quite likely to affect the results.

Background

Vitamin E occurs naturally in the diet. It has several biological activities, including functioning as an antioxidant to scavenge toxic free radicals. Evidence that free radicals may contribute to the pathological processes behind cognitive impairment has led to interest in the use of vitamin E supplements to treat mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This is an update of a Cochrane Review first published in 2000, and previously updated in 2006 and 2012.

Objectives

To assess the efficacy of vitamin E in the treatment of MCI and dementia due to AD.

Search methods

We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources on 22 April 2016 using the terms: “Vitamin E”, vitamin-E, alpha-tocopherol.

Selection criteria

We included all double-blind, randomised trials in which treatment with any dose of vitamin E was compared with placebo in people with AD or MCI.

Data collection and analysis

We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. Where appropriate we attempted to contact authors to obtain missing information.

Main results

Four trials met the inclusion criteria, but we could only extract outcome data in accordance with our protocol from two trials, one in an AD population (n = 304) and one in an MCI population (n = 516). Both trials had an overall low to unclear risk of bias. It was not possible to pool data across studies owing to a lack of comparable outcome measures.

In people with AD, we found no evidence of any clinically important effect of vitamin E on cognition, measured with change from baseline in the Alzheimer’s Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to 0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no evidence of a difference between vitamin E and placebo groups in the risk of experiencing at least one serious adverse event over six to 48months (risk ratio (RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1 study, n = 304; moderate quality evidence). People with AD receiving vitamin E showed less functional decline on the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory than people receiving placebo at six to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study, n = 280; moderate quality evidence). There was no evidence of any clinically important effect on neuropsychiatric symptoms measured with the Neuropsychiatric Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate quality evidence).

We found no evidence that vitamin E affected the probability of progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95% CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five deaths occurred in each of the vitamin E and placebo groups over the 36 months (RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality evidence). We were unable to extract data in accordance with the review protocol for other outcomes. However, the study authors found no evidence that vitamin E differed from placebo in its effect on cognitive function, global severity or activities of daily living. There was also no evidence of a difference between groups in the more commonly reported adverse events.

Authors’ conclusions

We found no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD. Vitamin E was not associated with an increased risk of serious adverse events or mortality in the trials in this review. These conclusions have changed since the previous update, however they are still based on small numbers of trials and participants and further research is quite likely to affect the results.

BACKGROUND: Vitamin D deficiency is common in older persons. The objectives of this study were: to examine the cross-sectional and longitudinal association between serum 25-hydroxyvitamin D (25(OH)D) and cognitive functioning in older persons; and to explore the optimal cut-off for serum 25(OH)D. METHODS: Data of the Longitudinal Aging Study Amsterdam (LASA) were used. Serum 25(OH)D was determined using a competitive protein binding assay in 1995/6 (n = 1,320). Cognitive functioning was assessed in 1995/6 and 1998/9 using the Mini-Mental State Examination (MMSE, general cognitive functioning), Raven's Colored Progressive Matrices (RCPM, ability of nonverbal and abstract reasoning), the Coding Task (CT, information processing speed), and the 15 Words Test (15WT, immediate memory and delayed recall). The data were analyzed using linear regression analyses and restricted cubic spline functions. The MMSE was normalized using ln(31-MMSE). RESULTS: Mean serum 25(OH)D was 53.7 nmol/L. After adjustment for confounding, patients with serum 25(OH)D levels below 30 nmol/L had significantly lower general cognitive functioning (beta of ln(31-MMSE) = 0.122; p = 0.046) and slower information processing speed (beta = -2.177, p = 0.001) as compared with patients having serum 25(OH)D levels ≥ 75 nmol/L in the cross-sectional analyses. For both outcomes, the optimal cut-off was about 60 nmol/L. No other significant associations were observed. CONCLUSIONS: a lower serum 25(OH)D was significantly associated with lower general cognitive functioning and slower information processing speed, but not with a faster rate of cognitive decline.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts a and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Emerging evidence suggests that low vitamin D concentrations are potentially involved in the pathogenesis of dementia. This is of particular interest when considering the high prevalence of vitamin D deficiency in elderly adults and the urgent need to identify modifiable risk factors for dementia. Studies have found that vitamin D is implicated in procognitive and neuroprotective functions, including the reduction of Alzheimer's disease hallmarks such as amyloid beta and phosphorylated tau. Cross-sectional studies have consistently found that vitamin D concentrations are significantly lower in individuals with Alzheimer's disease and cognitive impairment compared to healthy controls. Longitudinal studies support an association between low vitamin D concentrations and an increased risk of dementia and cognitive decline. Neuroimaging studies are beginning to uncover the potential neurodegenerative and cerebrovascular mechanisms that underlie these associations such as white matter hyperintensities and enlarged ventricular volume, although there is currently a lack of longitudinal studies. In contrast to observational studies, findings from interventional studies have produced mixed results on the benefits of vitamin D supplementation on dementia and cognitive outcomes. Interpretation of the findings from these studies is hampered by several major methodological limitations, such as small sample sizes, inadequate doses and inclusion of participants unlikely to benefit from vitamin D supplementation. There is a need for large double-blind randomised-control trials investigating whether vitamin D supplementation can halt or delay the risk of dementia-related outcomes in individuals with low vitamin D concentrations.

BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. OBJECTIVE: to investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. RESULTS: in the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.

Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (

OBJECTIVE: over three million people aged over 65 fall each year in the UK. Postural hypotension (PH) is a risk factor for falls. It is associated with excess mortality, and may affect cognition. PH is not routinely checked for in UK clinical practice. We studied the InCHIANTI dataset to derive and validate a simple prediction tool designed to facilitate identification of subjects to be checked for PH. DESIGN AND METHOD: InCHIANTI is a population-based study of ageing. It recruited subjects from population registries in Chianti, Italy in 1998 and they were followed up triennially. Blood pressure (BP) at recruitment was measured after resting supine, and one and three minutes after standing, using a mercury sphygmomanometer. Systolic PH was defined as a > = 20 mmHg fall in supine BP on standing. Subjects were randomised to derivation or validation cohorts; allocation was undertaken blinded to PH status and medical history. Candidate predictor variables identified from literature searches were tested for univariable cross sectional associations with PH using χ2 tests. Those with significant associations were entered into multivariable linear regression models, and used to derive simple and weighted prediction scores (DROP scores). DROP scores were tested in the validation cohort for prediction of PH, future falls, cognitive decline and mortality rates. RESULTS: PH was present in 56/726 (7.7%) of the derivation cohort and 45/727 (6.2%) of the validation cohort (p = 0.25). PH was associated with age > = 65, falls in the preceding year, diabetes, previous stroke, hypertension and Parkinson's disease. A simple score summing numbers of these variables performed equally well as weighted scores (AUROC 0.67 (0.59 to 0.74); p 

Background: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians. Methods: International experts met at an invitational summit on 'Vitamin D and Cognition in Older Adults'. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer's disease and related disorders. Each question was discussed and voted using a Delphi-like approach. Results: the experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer's disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of 'critical periods' during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered. Conclusions: the international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available.

BACKGROUND: Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer's disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not. METHODS: We conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies. RESULTS: the twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains. CONCLUSIONS: Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.

BACKGROUND: the aim of this article is to report the findings of a secondary analysis of a previous injury study to consider previous injury as a risk factor for reinjury in rock climbing. METHODS: We completed a secondary analysis of 201 questionnaires that were gathered as part of a retrospective cross-sectional cohort survey that investigated the epidemiology of injuries in a representative sample of British rock climbers. Participants had actively engaged in rock climbing over the previous 12-month period and were recruited from six indoor climbing centres and five outdoor climbing venues (men n=163, mean±SD, age=35.2±11.8�
years, participating in rock climbing=13.88+11.77�
years; women n=38, mean±SD, age=35.1±10.7�
years, participating in rock climbing=11.62+9.19�
years). RESULTS: of the 101 participants who sustained a previous injury, 36 were found to have sustained at least one reinjury. The total number of reinjuries was 82, with the average probability of sustaining at least one reinjury being 35.6% (95% CI 34.71% to 36.8%; p

BACKGROUND: US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. OBJECTIVE: to investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. METHODS: We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests a and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. RESULTS: the multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73-0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests a (RR = 0.85, 95% CI 0.71-1.02) and B (RR = 0.90, 0.79-1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. CONCLUSIONS: High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.

BACKGROUND: Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. METHODS: Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. RESULTS: Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12-72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. CONCLUSIONS: Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging.

Though frailty status has recently been linked to poorer quality of life, the impact of income on this relationship has not previously been investigated. Data from a population-based panel study, the English Longitudinal Study of Aging, on 3225 participants aged 65-79 years were analyzed cross-sectionally. A Frailty Index (FI) was determined for each participant as a proportion of accumulated deficits and participants were categorized into four groups on the basis of their FI score: very fit (0.00-0.10), well (0.11-0.14), vulnerable (0.15-0.24), and frail (≥0.25). Subjective well-being was assessed using the CASP-19 instrument, and levels of financial resources quantified using a range of questions about assets and income from a range of sources. Linear regression models were used to assess the relationship between frailty and well-being. There was a significant negative correlation between frailty and well-being; the correlation coefficient between FI and CASP-19 scores was -0.58. The relationship was robust to adjustment for sex, age, and relevant health behaviors (smoking and physical activity) and persisted when participants with depressive symptoms were excluded from analysis. Those with greater financial resources reported better subjective well-being with evidence of a "dose-response" effect. The poorest participants in each frailty category had similar well-being to the most well-off with worse frailty status. Hence, while the association between frailty and poorer subjective well-being is not significantly impacted by higher levels of wealth and income, financial resources may provide a partial buffer against the detrimental psychological effects of frailty. © 2014 Elsevier Ireland Ltd.

OBJECTIVE: to assess the effects of a history of alcohol use disorders (AUDs) on risk of severe cognitive and memory impairment in later life. METHODS: We studied the association between history of AUDs and the onset of severe cognitive and memory impairment in 6,542 middle-aged adults born 1931 through 1941 who participated in the Health and Retirement Study, a prospective nationally representative U.S. cohort. Participants were assessed at 1992 baseline and follow-up cognitive assessments were conducted biannually from 1996 through 2010. History of AUDs was identified using the three-item modified CAGE questionnaire. Cognitive outcomes were assessed using the 35-item modified Telephone Interview for Cognitive Status at last follow-up with incident severe cognitive impairment defined as a score ≤ 8, and incident severe memory impairment defined as a score ≤ 1 on a 20-item memory subscale. RESULTS: During up to 19 years of follow-up (mean: 16.7 years, standard deviation: 3.0, range: 3.5-19.1 years), 90 participants experienced severe cognitive impairment and 74 participants experienced severe memory impairment. History of AUDs more than doubled the odds of severe memory impairment (odds ratio [OR] = 2.21, 95% confidence interval [CI] = 1.27-3.85, t = 2.88, df = 52, p = 0.01). The association with severe cognitive impairment was statistically non-significant but in the same direction (OR = 1.80, 95% CI = 0.97-3.33, t = 1.92, df = 52, p = 0.06). CONCLUSION: Middle-aged adults with a history of AUDs have increased odds of developing severe memory impairment later in life. These results reinforce the need to consider the relationship between alcohol consumption and cognition from a multifactorial lifespan perspective.

Background

Increased life expectancy has resulted in a greater provision of informal care within the community for patients with chronic physical health conditions. Informal carers are at greater risk of poor mental health, with one in three informal carers of stroke survivors experiencing depression. However, currently no psychological treatments tailored to the unique needs of depressed informal carers of stroke survivors exist. Furthermore, informal carers of stroke survivors experience a number of barriers to attending traditional face-to-face psychological services, such as lack of time and the demands of the caring role. The increased flexibility associated with supported cognitive behavioral therapy self-help (CBTsh), such as the ability for support to be provided by telephone, email, or face-to-face, alongside shorter support sessions, may help overcome such barriers to access. CBTsh, tailored to depressed informal carers of stroke survivors may represent an effective and acceptable solution.
Methods

This study is a Phase II (feasibility) randomized controlled trial (RCT) following guidance in the MRC Complex Interventions Research Methods Framework. We will randomize a sample of depressed informal carers of stroke survivors to receive CBT self-help supported by mental health paraprofessionals, or treatment-as-usual. Consistent with the objectives of assessing the feasibility of trial design and procedures for a potential larger scale trial we will measure the following outcomes: a) feasibility of patient recruitment (recruitment and refusal rates); (b) feasibility and acceptability of data collection procedures; (c) levels of attrition; (d) likely intervention effect size; (e) variability in number, length and frequency of support sessions estimated to bring about recovery; and (f) acceptability of the intervention. Additionally, we will collect data on the diagnosis of depression, symptoms of depression and anxiety, functional impairment, carer burden, quality of life, and stroke survivor mobility skill, self-care and functional ability, measured at four and six months post-randomization.
Discussion

This study will provide important information for the feasibility and design of a Phase III (effectiveness) trial in the future. If the intervention is identified to be feasible, effective, and acceptable, a written CBTsh intervention for informal carers of stroke survivors, supported by mental health paraprofessionals, could represent a cost-effective model of care.

Trial registration: Current Controlled Trials ISRCTN63590486.

OBJECTIVE: to determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (

BACKGROUND: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS: in this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p

Vitamin D has been investigated in association with cognitive function in older adults. It is unclear whether hypovitaminosis D could be associated with Alzheimer's disease (AD). Our objective was to systematically review and quantitatively synthesize the association of low serum 25-hydroxyvitamin D (25OHD) concentrations with AD in adults. A Medline and PsycINFO® search was conducted on May 2012, with no limit of date, using the MeSH terms "Vitamin D" OR "Hydroxycholecalciferols" combined with the MeSH terms "Alzheimer disease" OR "Dementia" OR "Cognition" OR "Cognition disorders" OR "Memory" OR "Memory Disorders" OR "Executive Function" OR "Attention" OR "Neuropsychological Tests". of the 284 selected studies, 10 observational studies (including 9 case-controls and 1 cohort study) met the selection criteria. All were of good quality. The number of AD cases ranged from 20 to 211 (40%-100% female). Finally, 7 case-control studies were eligible for fixed and random-effects meta-analyses of bias-corrected effect size of the difference in serum 25OHD concentrations between AD cases and controls using an inverse-variance method. The pooled effect size in random-effects meta-analysis was 1.40 (95% CI: 0.26;2.54), a 'large' effect size that indicates that serum 25OHD concentrations were 1.4 standard deviation units lower in AD cases compared to cognitively healthy controls (p = 0.016). In conclusion, AD cases had lower serum vitamin D concentrations than matched controls. This reinforces the conceptualization of vitamin D as a 'neurosteroid hormone' and as a potential biomarker of AD.

BACKGROUND:: Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia. METHODS:: We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia. RESULTS:: Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent. CONCLUSIONS:: Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia. © 2013 Lippincott Williams & Wilkins.

BACKGROUND: Hypovitaminosis D is associated with global cognitive impairment in adults. It remains unclear which domain-specific cognitive functions are affected with hypovitaminosis D. OBJECTIVE: to systematically review and quantitatively synthesize the association of serum 25-hydroxyvitamin D (25OHD) concentrations with episodic memory and executive functions in adults. METHODS: a Medline and PsycINFO libraries search was conducted on May 2012, with no limit of date, using the Medical Subject Headings (MeSH) terms "Vitamin D" OR "Hydroxycholecalciferols" combined with the MeSH terms "Memory" OR "Memory Disorders" OR "Executive Function" OR "Attention" OR "Cognition" OR "Cognition disorders" OR "Dementia" OR "Alzheimer disease" OR "Neuropsychological Tests". Fixed-effects meta-analysis was performed from 12 eligible studies using an inverse-variance method. RESULTS: of the 285 selected studies, 14 observational studies (including 3 prospective cohort studies) and 3 interventional studies met the selection criteria. All were of good quality. The number of participants ranged from 44-5,692 community-dwellers (0-100% women). In the pooled analysis, although episodic memory disorders showed only modest association with lower 25OHD concentrations (summary effect size of the difference (ES) = -0.09 [95%CI:-0.16;-0.03]), associations of greater magnitude were found with executive dysfunctions (processing speed: mean difference of Trail Making Test (TMT)-A score = 4.0 [95% CI:1.20;6.83]; mental shifting: mean difference of TMT-B score = 12.47 [95% CI:6.78;18.16]; information updating tests: ES = -0.31 [95% CI:-0.5;-0.09]). The pooled risk of incident decline of TMT-B score was OR = 1.25 [95% CI:1.05;1.48] in case of initial lower 25OHD concentrations. Vitamin D repletion resulted in improved executive functions (ES = -0.50 [95% CI:-0.69;-0.32] for before-and-after comparison), but exhibited no difference with control groups (ES = 0.14 [95% CI:-0.04;0.32] for between-group comparison after intervention). CONCLUSION: Lower serum 25OHD concentrations predict executive dysfunctions, especially on mental shifting, information updating and processing speed. The association with episodic memory remains uncertain.

OBJECTIVES: Past research has shown that parental longevity is related to offspring physical health and longevity. Preliminary studies suggest that parental longevity may be linked to the offspring's personality traits. A comprehensive 5-factor personality model has been related to physical health, but the association with parental longevity has not yet been investigated. We used a 5-factor personality model to investigate the relationship between parental longevity and offspring personality. METHOD: Data from the longitudinal Health and Retirement Study (HRS) was used in the analyses. Using the Midlife Development Inventory and the Life Orientation test, the relationship between parental attained age and offspring personality was assessed using regression models for both men and women. RESULTS: Male offspring of long-lived fathers and mothers were more likely to be open to new experiences (p <. 01) and be more extroverted (p =. 03) compared with male offspring of short-lived fathers or mothers. Maternal or paternal attained age had no effect on the female offspring personality traits. DISCUSSION: Personality is an important phenotype to consider when investigating genetic and environmental determinants of longevity. Further research is needed to investigate the potential of gender-specific mechanisms.

BACKGROUND: Improved life expectancy is resulting in increased outpatient treatment of people with chronic physical health conditions and reliance on the provision of informal care in the community. However, informal care is also associated with increased risk of experiencing common mental health difficulties such as depression and anxiety. Currently there is a lack of evidence-based treatments for such difficulties, resulting in poor health outcomes for both the informal carer and care recipient. METHODS/DESIGN: Electronic databases will be systemically searched for randomised controlled trials examining the effectiveness of psychological interventions targeted at treating depression or anxiety experienced by informal carers of patients with chronic physical health conditions. Database searches will be supplemented by contact with experts, reference and citation checking and grey literature. Both published and unpublished research in English language will be reviewed with no limitations on year or source. Individual, group and patient-carer dyad focused interventions will be eligible. Primary outcomes of interest will be validated self-report or clinician administered measures of depression or anxiety. If data allows a meta-analysis will examine: (1) the overall effectiveness of psychological interventions in relation to outcomes of depression or anxiety; (2) intervention components associated with effectiveness. DISCUSSION: This review will provide evidence on the effectiveness of psychological interventions for depression and anxiety experienced by informal carers of patients with chronic physical health conditions. In addition, it will examine intervention components associated with effectiveness. Results will inform the design and development of a psychological intervention for carers of people with chronic physical health conditions experiencing depression and anxiety. PROSPERO registration number: CRD42012003114.

Background: Optimal vitamin D intake and its status are important not only for bone and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and insufficiency as a global health problem are likely to be a risk for wide spectrum of acute and chronic illnesses. Methods: a review of randomized controlled trials, meta-analyses, and other evidence of vitamin D action on various health outcomes. Results: Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality. Conclusions: Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders. Supplementation guidance and population strategies for the eradication of vitamin D deficiency must be included in the priorities of physicians, medical professionals and healthcare policy-makers. © 2013 Elsevier B.V.

On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. Introduction: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g. the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. Methods: to exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. Results: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. Conclusion: to reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg (800 IU), which is best achieved with a supplement. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

UNLABELLED: on September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. INTRODUCTION: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g. the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. METHODS: to exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. RESULTS: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. CONCLUSION: to reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg (800 IU), which is best achieved with a supplement.

BACKGROUND: Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned. METHODS: Here, we review age-related disease associated single-nucleotide polymorphisms and identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control. RESULTS: Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the "fine tuning" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively. CONCLUSIONS: the emerging clearer picture of the genetic architecture of age-related diseases in humans is providing new insights into the underlying pathophysiological pathways involved. Translation of genomics into new approaches to prevention, tests and treatments to extend successful aging is therefore likely in the coming decades.

INTRODUCTION: Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample. METHODS: We measured in vivo transcript levels by microarray analysis in 691 subjects (mean age 72.6 years) in the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area). We assessed expression associations with MMSE performance at RNA collection and prior 9-year change in MMSE score in linear regression models. RESULTS: in genome-wide analysis, raised CCR2 expression was cross-sectionally the most strongly associated transcript with lower MMSE score (beta=-0.16, p=5.1×10(-6), false discovery rate (FDR; q=0.077). Amongst inflammatory transcripts, only CCR2 expression was associated with both MMSE score and accelerated decline in score over the preceding 9 years (beta=-0.16, p=5.1×10(-6), q=0.003; and beta=-0.13, p=5.5×10(-5), q=0.03, respectively). CCR2 expression was also positively associated with apolipoprotein E (ApoE) e4 Alzheimer disease risk haplotype. CONCLUSIONS: We show for the first time that CCR2 expression is associated with lower MMSE scores in an older human population. Laboratory models of Ccr2-mediated β-amyloid removal and regulation of neurogenesis affecting cognitive function may be applicable in humans. CCR2-mediated pathways may provide a possible focus for intervention to potentiate protective reactions to Alzheimer pathology in older people, including for people with an adverse ApoE haplotype.

Whether mild cognitive impairment (MCI) has a distinct neuropathological profile that reflects an intermediate state between no cognitive impairment and dementia is not clear. Identifying which biological events occur at the earliest stage of progressive disease and which are secondary to the neuropathological process is important for understating pathological pathways and for targeted disease prevention. Many studies have now reported on the neurobiology of this intermediate stage. In this systematic review, we synthesize current evidence on the neuropathological profile of MCI. A total of 162 studies were identified with varied definition of MCI, settings ranging from population to specialist clinics and a wide range of objectives. From these studies, it is clear that MCI is neuropathologically complex and cannot be understood within a single framework. Pathological changes identified include plaque and tangle formation, vascular pathologies, neurochemical deficits, cellular injury, inflammation, oxidative stress, mitochondrial changes, changes in genomic activity, synaptic dysfunction, disturbed protein metabolism and disrupted metabolic homeostasis. Determining which factors primarily drive neurodegeneration and dementia and which are secondary features of disease progression still requires further research. Standardization of the definition of MCI and reporting of pathology would greatly assist in building an integrated picture of the clinical and neuropathological profile of MCI. © 2012 Macmillan Publishers Limited all rights reserved.

The role of vitamin D in skeletal health is well established, but more recent findings have also linked vitamin D deficiency to a range of non-skeletal conditions such as cardiovascular disease, cancer, stroke and metabolic disorders including diabetes. Cognitive impairment and dementia must now be added this list. Vitamin D receptors are widespread in brain tissue, and vitamin D's biologically active form [1,25(OH)(2)D3] has shown neuroprotective effects including the clearance of amyloid plaques, a hallmark of Alzheimer's Disease. Associations have been noted between low 25-hydroxyvitamin D [25(OH)D] and Alzheimer's disease and dementia in both Europe and the US. Similarly, the risk of cognitive impairment was up to four times greater in the severely deficient elders (25(OH)D < 25 nmol/L) in comparison with individuals with adequate levels (≥ 75 nmol/L). Further studies have also shown associations between low 25(OH)D concentrations and cerebrovascular events such as large vessel infarcts, risk of cerebrovascular accident and fatal stroke. Cross-sectional studies cannot establish temporal relationships because cognitive decline and the onset of dementia itself may influence vitamin D concentrations through behavioural and dietary changes. However, two large prospective studies recently indicated that low vitamin D concentrations may increase the risk of cognitive decline. Large, well designed randomized controlled trials are now needed to determine whether vitamin D supplementation is effective at preventing or treating Alzheimer's disease and dementia.

OBJECTIVE: to examine the association between cognitive function and dementia with vitamin D concentration in adults. METHODS: Five databases were searched for English-language studies up to August 2010, and included all study designs with a comparative group. Cognitive function or impairment was defined by tests of global or domain-specific cognitive performance and dementia was diagnosed according to recognized criteria. A vitamin D measurement was required. Two authors independently extracted data and assessed study quality using predefined criteria. The Q statistic and I² methods were used to test for heterogeneity. We conducted meta-analyses using random effects models for the weighted mean difference (WMD) and Hedge's g. RESULTS: Thirty-seven studies were included; 8 contained data allowing mean Mini-Mental State Examination (MMSE) scores to be compared between participants with vitamin D

OBJECTIVES: to compare the characteristics and outcomes of caregivers of adults with dementia with those of caregivers of adults with cognitive impairment, not dementia (CIND). DESIGN: Cross-sectional. SETTING: In-home assessment for cognitive impairment and self-administered caregiving questionnaire. PARTICIPANTS: One hundred sixty-nine primary family caregivers of participants in the Aging, Demographics, and Memory Study (ADAMS). ADAMS participants were aged 71 and older drawn from the nationally representative Health and Retirement Study. MEASUREMENTS: Neuropsychological testing, neurological examination, clinical assessment, and medical history were used to assign a diagnosis of normal cognition, CIND, or dementia. Caregiving measures included caregiving time, functional limitations, depressive symptoms, physical and emotional strain, caregiving rewards, caregiver health, and demographic characteristics. RESULTS: Dementia caregivers spent approximately 9 hours per day providing care, compared with 4 hours per day for CIND caregivers (P=.001). Forty-four percent of dementia caregivers exhibited depressive symptoms, compared with 26.5% of CIND caregivers (P=.03). Physical and emotional strains were similar in both groups of caregivers. Regardless of the strains, nearly all caregivers reported some benefits from providing care. Behavioral problems (P=.01) and difficulty with instrumental activities of daily living (P=.01) in persons with CIND partially explained emotional strain experienced by CIND caregivers. For those with dementia, behavioral problems predicted caregiver emotional strain (P

BACKGROUND: the prevalence of psychological distress and common mental disorders has been shown to peak in midlife but analyses have ignored the association of poor material circumstances with prevalence. This study aimed to test the hypothesis that the midlife prevalence peak occurs only in lower-income households. METHOD: Pooled data were used from the annual Health Survey for England, a nationally representative cross-sectional study, on community-dwelling individuals aged ≥ 16 years from years 1997 to 2006 (n=100 457). 12-item General Health Questionnaire scores, reported mental illness diagnoses and receipt of relevant medication were assessed in relation to household income and age. Analyses were separated by gender and adjusted for age, ethnicity, smoking, social class, education and co-morbidities. RESULTS: Prevalence of psychological distress, diagnoses and treatments rose with age until early middle age and declined subsequently. In analyses conducted separately by income categories, this pattern was marked in low-income groups but absent in high-income groups. Income-related inequalities in the prevalence of psychological distress were greatest in midlife; for example, in men aged 45-54 years the odds ratio of receiving psychiatric medication in the lowest income group compared with the highest was 7.50 [95% confidence interval (CI) 4.24-13.27] and in women aged 45-54 years the odds ratio of reporting mental illness was 10.25 (95% CI 6.16-17.05). CONCLUSIONS: an increased prevalence of psychological distress, common mental disorder diagnoses and treatment in midlife is not a universal phenomenon but is found only in those in low-income households. This implies the phenomenon is not inevitable but is potentially manageable or preventable.

OBJECTIVES: to examine the association between neuropsychiatric symptoms and risk of institutionalization and death. DESIGN: Analysis of longitudinal data. SETTING: the Aging, Demographics, and Memory Study (ADAMS). PARTICIPANTS: Five hundred thirty-seven adults aged 71 and older with cognitive impairment drawn from the Health and Retirement Study (HRS). MEASUREMENTS: Neuropsychiatric symptoms (delusions, hallucinations, agitation, depression, apathy, elation, anxiety, disinhibition, irritation, and aberrant motor behaviors) and caregiver distress were identified using the Neuropsychiatric Inventory. A consensus panel in the ADAMS assigned cognitive category. Date of nursing home placement and information on death, functional limitations, medical comorbidity, and sociodemographic characteristics were obtained from the HRS and ADAMS. RESULTS: Overall, the presence of one or more neuropsychiatric symptoms was not associated with a significantly higher risk for institutionalization or death during the 5-year study period, although when assessing each symptom individually, depression, delusions, and agitation were each associated with a significantly higher risk of institutionalization (hazard rate (HR)=3.06, 95% confidence interval (CI)=1.09-8.59 for depression; HR=5.74, 95% CI=1.94-16.96 for clinically significant delusions; HR=4.70, 95% CI=1.07-20.70 for clinically significant agitation). Caregiver distress mediated the association between delusions and agitation and institutionalization. Depression and hallucinations were associated with significantly higher mortality (HR=1.56, 95% CI=1.08-2.26 for depression; HR=2.59, 95% CI=1.09-6.16 for clinically significant hallucinations). CONCLUSION: Some, but not all, neuropsychiatric symptoms are associated with a higher risk of institutionalization and death in people with cognitive impairment, and caregiver distress also influences institutionalization. Interventions that better target and treat depression, delusions, agitation, and hallucinations, as well as caregiver distress, may help delay or prevent these negative clinical outcomes.

OBJECTIVES: to identify predictors of extraordinary survival. DESIGN: Longitudinal study of a cohort of elderly people followed up until almost all have died. SETTING: Two counties in Iowa; a part of the Established Populations for Epidemiologic Study of the Elderly. PARTICIPANTS: Two thousand eight hundred ninety community-dwelling citizens aged 65 to 85 at baseline and surviving at least 3 years. MEASUREMENTS: Data relating to age, sex, birth order, parental longevity, marital status, education, family income, social support, self-reported health, chronic diseases, blood pressure, body mass index, physical ability, exercise, life attitude and mental health were obtained. Extraordinary survivors (ESs) were defined to include approximately 10% of the longest survivors in their sex group. RESULTS: the 253 ESs were far more likely never to have smoked. In models adjusted for age, sex, and smoking, the earlier-life factors such as parental longevity, being earlier in the birth order (in women only), and body mass index at age 50 were associated with extraordinary survival. In similar models for predictors at age 65 to 85, extraordinary survival was associated with excellent self-reported health, fewer chronic diseases, better physical mobility and memory, and positive attitude toward life, but it was not associated with depression, anxiety, or sleep quality. In multivariable models, attitude toward life was not an independent predictor. Women in the top third of a cumulative score of independent predictors were 9.3 (95% confidence interval=4.4-19.6, P

Background: Recent European studies suggest that vitamin D deficiency may be associated with increased odds of cognitive impairment in older persons, although findings from the United States are equivocal. Our objective was to investigate the association between vitamin D deficiency and cognitive impairment in the elderly U.S. population. Methods: Three thousand and three hundred twenty-five adults aged 65 years or more completed cognitive assessments, medical examinations, and physical performance measures and provided blood samples in the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional study of the U.S. noninstitutionalized population. We determined whether low levels of serum 25-hydroxyvitamin D (25(OH)D) were associated with increased odds of cognitive impairment using logistic regression models. Cognitive impairment was assessed using measures of immediate and delayed verbal memory, orientation, and attention (impairment was defined as the worst 10% of the distribution of combined scores). Results: the multivariate adjusted odds ratios (95% confidence interval) of cognitive impairment in participants who were 25(OH)D insufficient (≥50 < 75 nmol/L), deficient (≥25 < 50 nmol/L), and severely deficient (

BACKGROUND: Recent European studies suggest that vitamin D deficiency may be associated with increased odds of cognitive impairment in older persons, although findings from the United States are equivocal. Our objective was to investigate the association between vitamin D deficiency and cognitive impairment in the elderly U.S. population. METHODS: Three thousand and three hundred twenty-five adults aged 65 years or more completed cognitive assessments, medical examinations, and physical performance measures and provided blood samples in the Third National Health and Nutrition Examination Survey, a nationally representative cross-sectional study of the U.S. noninstitutionalized population. We determined whether low levels of serum 25-hydroxyvitamin D (25(OH)D) were associated with increased odds of cognitive impairment using logistic regression models. Cognitive impairment was assessed using measures of immediate and delayed verbal memory, orientation, and attention (impairment was defined as the worst 10% of the distribution of combined scores). RESULTS: the multivariate adjusted odds ratios (95% confidence interval) of cognitive impairment in participants who were 25(OH)D insufficient (≥ 50 < 75 nmol/L), deficient (≥ 25 < 50 nmol/L), and severely deficient (

The physiologically active form of vitamin D, 1,25-dihydroxyvitamin D(3), is a fat-soluble steroid hormone with a well established role in skeletal health. A growing body of evidence suggests low vitamin D levels also play a role in the pathogenesis of a wide range of non-skeletal, age-associated diseases including cancer, heart disease, type 2 diabetes mellitus and stroke. Low levels of serum 25-hydroxyvitamin D [25(OH)D], a stable marker of vitamin D status, are also associated with increased odds of prevalent cognitive dysfunction, Alzheimer's disease and all-cause dementia in a number of studies, raising the possibility that vitamin D plays a role in the aetiology of cognitive dysfunction and dementia. To date, the majority of human studies reporting associations between vitamin D and cognition or dementia have been cross-sectional or case-control designs that do not permit us to exclude the possibility that such associations are a result of disease progression rather than being causal. Animal and in vitro experiments have identified a number of neuroprotective mechanisms that might link vitamin D status to cognitive dysfunction and dementia, including vasoprotection and amyloid phagocytosis and clearance, but the clinical relevance of these mechanisms in humans is not currently clear. Two recent, large, prospective studies go some way to establish the temporal relationship with cognitive decline. The relative risk of cognitive decline was 60% higher (relative risk = 1.6, 95% CI 1.2, 2.0) in elderly Italian adults with severely deficient 25(OH)D levels (

CONTEXT: Depression negatively affects health and well being among older adults, but there have been no nationally representative comparisons of depression prevalence among older adults in England and the United States. OBJECTIVE: the authors sought to compare depressive symptoms among older adults in these countries and identify sociodemographic and clinical correlates of depression in these countries. DESIGN AND SETTING: the authors assessed depressive symptoms in non-Hispanic whites aged 65 years and older in 2002 in two nationally representative, population-based studies: the U.S. Health and Retirement Study and English Longitudinal Study of Ageing. PARTICIPANTS: a total of 8,295 Health and Retirement Study respondents and 5,208 English Longitudinal Study of Ageing respondents. MAIN OUTCOME MEASURES: the authors measured depressive symptoms using the eight-item Center for Epidemiologic Studies Depression Scale. The authors determined whether depressive symptom differences between the United States and England were associated with sociodemographic characteristics, chronic health conditions, and health behaviors. RESULTS: Significant depressive symptoms (Center for Epidemiologic Studies Depression Scale score ≥4) were more prevalent in English than U.S. adults (17.6% versus 14.6%, adjusted Wald test F([1, 1593]) = 11.4, p < 0.001). Adjusted rates of depressive symptoms in England were 19% higher compared with the United States (odds ratio: 1.19, 95% confidence interval: 1.01-1.40). U.S. adults had higher levels of education, and net worth, but lower levels of activities of daily living/instrumental activities of daily living impairments, tobacco use, and cognitive impairment, which may have contributed to relatively lower levels of depressive symptoms in the United States. CONCLUSIONS: Older adults in the United States had lower rates of depressive symptoms than their English counterparts despite having more chronic health conditions. Future cross-national studies should identify how depression treatment influences outcomes in these populations.

Background. Frailty has been conceptualized as a wasting disorder with weight loss as a key component. However, obesity is associated with disability and with physiological markers also recently linked with frailty, for example, increased inflammation and low antioxidant capacity. We aimed to explore the relationship between frailty and body mass index (BMI) in older people. Methods Data were from 3,055 community-dwelling adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. Frailty was defined both by an index of accumulated deficits and by the Fried phenotype. BMI was divided into five categories, and waist circumference 88 cm or more (for women) and 102 cm or more (for men) was defined as high. Analyses were adjusted for sex, age, wealth, level of education, and smoking status. Results the association between BMI and frailty showed a U-shaped curve. This relationship was consistent across different frailty measures. The lowest frailty index (FI) scores and lowest prevalence of Fried frailty were in those with BMI 25-29.9. At each BMI category, and using either measure of frailty, those with a high waist circumference were significantly more frail. Conclusions Both the phenotypic definition of frailty and the FI show increased levels of frailty among those with low and very high BMIs. In view of the rise in obesity in older populations, the benefits and feasibility of diet and exercise for obese older adults should be a focus of urgent inquiries. The association of frailty with a high waist circumference, even among underweight older people, suggests that truncal obesity may be an additional target for intervention. © the Author 2009. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved.

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

The purpose of the present study was to assess the relationship between pre-performance psychological states and expert performance in non-traditional sport competition. Nineteen elite male sport climbers (M=24.6, SD=4.0 years of age) completed the Competitive State Anxiety Inventory-2 and the Positive and Negative Affect Schedule before an international rock climbing competition. Climbing performances were video-recorded to calculate movement fluency (entropy) and obtain ascent times. Official route scores were also obtained. Successful climbers reported higher pre-performance levels of somatic anxiety and climbed the most difficult part of the route more slowly than their unsuccessful counterparts. The psychological states preceding elite climbing competition appeared to be an important factor in determining success, even when differences in baseline ability were taken into account.

OBJECTIVES: to estimate the prevalence of neuropsychiatric symptoms and examine their association with functional limitations. DESIGN: Cross-sectional analysis. SETTING: the Aging, Demographics, and Memory Study (ADAMS). PARTICIPANTS: a sample of adults aged 71 and older (N=856) drawn from Health and Retirement Study (HRS), a nationally representative cohort of U.S. adults aged 51 and older. MEASUREMENTS: the presence of neuropsychiatric symptoms (delusions, hallucinations, agitation, depression, apathy, elation, anxiety, disinhibition, irritation, and aberrant motor behaviors) was identified using the Neuropsychiatric Inventory. A consensus panel in the ADAMS assigned a cognitive category (normal cognition; cognitive impairment, no dementia (CIND); mild, moderate, or severe dementia). Functional limitations, chronic medical conditions, and sociodemographic information were obtained from the HRS and ADAMS. RESULTS: Forty-three percent of individuals with CIND and 58% of those with dementia exhibited at least one neuropsychiatric symptom. Depression was the most common individual symptom in those with normal cognition (12%), CIND (30%), and mild dementia (25%), whereas apathy (42%) and agitation (41%) were most common in those with severe dementia. Individuals with three or more symptoms and one or more clinically significant symptoms had significantly higher odds of having functional limitations. Those with clinically significant depression had higher odds of activity of daily living limitations, and those with clinically significant depression, anxiety, or aberrant motor behaviors had significantly higher odds of instrumental activity of daily living limitations. CONCLUSION: Neuropsychiatric symptoms are highly prevalent in older adults with CIND and dementia. of those with cognitive impairment, a greater number of total neuropsychiatric symptoms and some specific individual symptoms are strongly associated with functional limitations.

Results from clinical samples suggest low serum albumin may be associated with cognitive impairment, though evidence from population-based studies is inconclusive. Participants were 1,752 adults (699 men and 1,053 women) aged 65 years and over from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum albumin quartiles to cognitive impairment was modelled using logistic regression. Two hundred and twelve participants were cognitively impaired (68 men and 144 women). Odds ratios (95% confidence intervals) for cognitive impairment in the first (2.2-3.8 g/dl), second (3.9-4.0 g/dl), and third (4.1-4.3 g/dl) quartiles of serum albumin compared with the fourth (4.4-5.3 g/dl) were 2.5 (1.3-5.1), 1.7 (0.9-3.5), and 1.5 (0.7-2.9), after adjustment for age, sex, education and additional risk factors for cognitive impairment (p for linear trend = 0.002). A highly similar pattern of associations was observed for men and women. Our data provide new evidence to suggest that low serum albumin is independently associated with increased odds of cognitive impairment in the elderly population.

INTRODUCTION: Evidence from clinical samples and geographically limited population studies suggests that vascular health, diabetes and apolipoprotein epsilon4 (APOE) are associated with dementia. METHODS: a population-based sample of 856 individuals aged 71 years or older from all contiguous regions of the United States received an extensive in-home clinical and neuropsychological assessment in 2001-2003. The relation of hypertension, diabetes, heart disease, stroke, medication usage, and APOE epsilon4 to dementia was modelled using adjusted multivariable logistic regression. RESULTS: Treated stroke (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.0, 7.2), untreated stroke (OR 3.5, 95% CI 1.7, 7.3), and APOE epsilon4 (OR 2.8, 95% CI 1.7, 4.5) all increased the odds of dementia. Treated hypertension was associated with lower odds of dementia (OR 0.5, 95% CI 0.3, 1.0). Diabetes and heart disease were not significantly associated with dementia. A significant interaction was observed between APOE epsilon4 and stroke (P = 0.001). CONCLUSIONS: Data from the first dementia study that is representative of the United States population suggest that stroke, the APOE epsilon4 allele and their interaction are strongly associated with dementia.

BACKGROUND: to our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests a and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS: the multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels /=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

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: the diagnosis of cognitive impairment and dementia must reflect an increasingly diverse and aging United States population. This study compared direct testing and informant reports of cognition with clinical diagnoses of cognitive impairment and dementia between African Americans and whites. METHODS: Participants in the Aging, Demographics, and Memory Study completed in-person dementia evaluations, and were assigned clinical diagnoses (by a consensus panel of dementia experts) of normal; cognitive impairment, not demented (CIND); and dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used to assess cognitive performance and reported cognitive decline. RESULTS: a higher CERAD total score was associated with lower odds of CIND and dementia, at comparable ratios between African Americans and whites. Higher IQCODE scores were associated with increased odds of dementia in both African Americans and whites. Higher IQCODE scores were associated with increased odds of CIND among whites, but not among African Americans. CONCLUSIONS: Cultural differences may influence informant reports of prevalent CIND and dementia. Our findings also highlight the need for more comparative research to establish the cultural validity of measures used to diagnose these conditions.

Objective to examine the association between a biomarker of exposure to secondhand smoke (salivary cotinine concentration) and cognitive impairment. Design Cross sectional analysis of a national population based study. Setting Stratified random sample of households throughout England. Participants 4809 non-smoking adults aged 50 years or more from the 1998,1999, and 2001 waves of the Health Survey for England who also participated in the 2002 wave of the English Longitudinal Study of Ageing and provided saliva samples for cotinine assay and a detailed smoking history. Main outcome measure Cognitive impairment as defined by the lowest 10% of scores on a battery of neuropsychological tests. Results Participants who did not smoke, use nicotine products, or have salivary cotinine concentrations of 14.1 ng/mlormore were divided into four equal size groups on the basis of cotinine concentrations. Compared with the lowestfourth of cotinine concentration (0.0-0.1 ng/ml)the odds ratios (95% confidence intervals) for cognitive impairment in the second (0.2-0.3 ng/ml), third (0.4-0.7 ng/ml), and highest fourths (0.8-13.5 ng/ml) were 1.08 (0.78 to 1.48), 1.13 (0.81 to 1.56), and 1.44 (1.07 to 1.94; P for trend 0.02), after adjustment for a wide range of established riskfactors for cognitive impairment. A similar pattern of associations was observed for never smokers and former smokers. Conclusions Exposure to secondhand smoke may be associated with increased odds of cognitive impairment. Prospective nationally representative studies relating biomarkers of exposure to cognitive decline and risk of dementia are needed.

Analyses incorporating large independent population-based samples and identical measures are needed to investigate recent trends in cognitive function. Nationally representative independent cohorts of community living individuals in England aged 65 years or older from the MRC Cognitive Function and Ageing Study in 1991 (n = 9458) and the English Longitudinal Study of Ageing in 2002 (n = 5196) were compared. East Cambridgeshire participants aged 65-69 years in 1991 (n = 680) were also compared to an independent cohort examined in 1996 (n = 600). Semantic verbal fluency, as measured by the animal naming neuropsychological test, increased by 1.1 extra words a minute in England between 1991 and 2002 (95% CI 0.9, 1.3). A similar increase was also observed in East Cambridgeshire. Levels of semantic verbal fluency appear to have increased in the older English population, which may help to buffer the aging population from future increases in dementia.

OBJECTIVES: to assess how individual socioeconomic status and neighborhood deprivation affect frailty. DESIGN: Nationally representative population-based study, the English Longitudinal Study of Aging (ELSA), analyzed cross-sectionally. PARTICIPANTS: Four thousand eight hundred eighteen individuals aged 65 and older. MEASUREMENTS: Outcome was a frailty index (FI), based on 58 potential deficits, with a theoretical range from 0 to 1; exposures were individual wealth and neighborhood deprivation (lack of local resources, financial and otherwise), based on a set of standard indicators. RESULTS: the FI score varied independently according to wealth and neighborhood deprivation. The mean FI score for an individual in the highest 20% of wealth and least deprived 20% of neighborhoods was 0.09 (95% confidence interval (CI)=0.09-0.09) and for an individual in the lowest 20% of wealth and most deprived 20% of neighborhoods was 0.17 (95% CI=0.16-0.17). CONCLUSION: Frailty in older adults is independently associated with individual and neighborhood socioeconomic factors. Older adults who are poor and live in deprived neighborhoods are most vulnerable. Policies and interventions intended to prevent or reduce frailty must take into account individual circumstances and the broader social settings in which individuals are located.

We investigated the relation between parental education and dementia in the United States. Participants in the Aging, Demographics, and Memory Study were included, with information regarding parental education obtained from the Health and Retirement Study. The odds of dementia in elderly Americans whose mothers had less then 8 years of schooling were twice (95% CI, 1.1-3.8) that of individuals with higher maternal education, when adjusted for paternal education. of elderly Americans with less educated mothers, 45.4% (95% CI, 37.4-53.4%) were diagnosed with dementia or ;;cognitive impairment, no dementia'' compared to 31.2% (95% CI, 25.0-37.4%) of elderly Americans whose mothers had at least an 8th grade education. The population attributable risk of dementia due to low maternal education was 18.8% (95% CI, 9.4-28.2%). The education of girls in a population may be protective of dementia in the next generation.

Vitamin D may be of interest in the prevention of cognitive impairment, though previous findings are inconclusive. Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25-hydroxyvitamin D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8-30 nmol/L), second (31-44 nmol/L), and third (45-65 nmol/L) quartiles of serum 25-hydroxyvitamin D compared with the fourth (66-170 nmol/L) were 2.3 (1.4-3.8), 1.4 (0.8-2.4), and 1.1 (0.6-1.9), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend =. 001). Our data suggest low serum 25-hydroxyvitamin D is associated with increased odds of cognitive impairment.

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.

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.

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.

OBJECTIVE: to assess whether incident mobility disability and neighbourhood deprivation in older people are associated independent of the effects of individual socio-economic status, health behaviours and health status. METHODS: prospective cohort study with a 2-year follow-up. SETTING: the English Longitudinal Study of Ageing (ELSA), a national probability sample of non-institutionalised older people. PARTICIPANTS: 4,148 participants aged 60 years and over. MEASUREMENTS: exposure was a census-based index of neighbourhood deprivation [the Index of Multiple Deprivation (IMD)]; outcomes were measured and self-reported incident mobility difficulties. RESULTS: neighbourhood deprivation had a statistically significant effect on physical function following adjustment for individual socio-economic factors, health behaviours and health status. Compared to those living in the least deprived 20% of neighbourhoods, those in the most deprived neighbourhoods had a risk ratio (RR) of incident self-reported mobility difficulties of 1.75 (95% CI 1.14-2.70) and RR of incident-impaired gait speed of 1.63 (95% CI 1.01-2.62). In adjusted models, 4.0 per 100 (95% CI 3.0-5.4) older adults in neighbourhoods in the least deprived 20% had incident mobility difficulties over a 2-year period, whereas 13.6 per 100 (95% CI 10.5-17.4) older adults had incident mobility difficulties in neighbourhoods in the most deprived 20%. CONCLUSIONS: older people living in deprived neighbourhoods are significantly more likely to experience incident mobility difficulties than those in less-deprived neighbourhoods. The mechanisms underlying this relationship are unclear and research to identify mechanisms and appropriate interventions is needed.

OBJECTIVES: to estimate the effects of excess body weight on objective and subjective physical function and mortality risks in noninstitutionalized older adults. DESIGN: Population-based cohort study. SETTING: the English Longitudinal Study of Ageing (ELSA). PARTICIPANTS: Three thousand seven hundred ninety-three participants in the ELSA aged 65 and older followed up for 5 years. MEASUREMENTS: Analyses compared the risks of impaired physical function and mortality for subjects who were at the recommended weight (body mass index (BMI)=20.0-24.9) with those who were overweight (BMI=25.0-29.9), obese (BMI=30.0-34.9) or severely obese (BMI>or=35.0). Outcome measures were difficulties with activities of daily living (ADLs), score on the Short Physical Performance Battery, and mortality. RESULTS: Participants in higher BMI categories had greater risk of impaired physical function at follow-up but little or no greater risk of mortality. For example, compared with men of recommended weight, obese men (BMI=30.0-34.9) had relative risk ratios of difficulties with ADLs of 1.99 (95% confidence interval (CI)=1.42-2.78), of measured functional impairment of 1.51 (95% CI=1.05-2.16), and of mortality of 0.99 (95% CI=0.60-1.61). Findings were robust when excluding those who lost weight, smoked, or had poor self-rated health. CONCLUSION: Excess body weight in people aged 65 and older is associated with greater risk of impaired physical function but not with greater mortality risk. Societies with growing numbers of overweight and obese older people are likely to face increasing burdens of disability-associated health and social care costs.

Self-efficacy may be associated with high risk behaviors in climbers operating at outdoor venues, though little is known about climbers recruited at indoor venues or less risky forms of rock climbing. Two-hundred and one active rock climbers (163 male) aged 16-62 years were recruited at five outdoor and six indoor climbing venues in Britain in a retrospective study. The relationship of self-efficacy to the frequency and difficulty of high and medium risk rock climbing behaviors was modelled using linear regression. Climbers high in self-efficacy engaged in both high and medium risk forms of rock climbing more frequently (β ≥ 0.18, 95% confidence interval [CI] 0.04-0.32) and at a higher level of difficulty (β ≥ 0.20, 95% CI 0.04-0.36). These associations were attenuated slightly with adjustment for covariates, though all remained significant. The same pattern of associations was observed for climbers recruited at indoor and outdoor venues, and for male and female climbers. Rock climbers may therefore participate more frequently, take calculated additional risks and attempt harder climbs when they feel confident in their abilities and are high in self-efficacy. Researchers should not assume psychological or behavioral homogeneity within risk taking populations. © 2008 Elsevier Ltd. All rights reserved.

OBJECTIVES: to determine the prevalence and nature of rock-climbing injuries, and the factors associated with these injuries. DESIGN: a retrospective cross-sectional study. SETTING: Rock climbers were recruited at five outdoor and six indoor climbing venues in the UK. PARTICIPANTS: 201 active rock climbers (163 male, 38 female climbers) aged 16-62 years. ASSESSMENT OF RISK FACTORS: Rock climbing behaviours and key demographics. MAIN OUTCOME MEASURES: Injuries requiring medical attention or withdrawal from participation for > or = 1 day. RESULTS: Around 50% of climbers had sustained > or = 1 injury in the past 12 months, causing a total of 275 distinct anatomical injuries. 21 climbers (10%) had sustained acute climbing injuries as a result of a fall, 67 (33%) had chronic overuse injuries, and 57 (28%) had acute injuries caused by strenuous climbing moves. Dedicated climbers participating in different forms of rock climbing more often and at a higher level of technical difficulty may be more prone to injury, particularly overuse injuries of the finger and shoulder. The principal sources of treatment or advice sought by climbers were physiotherapists (18%), other climbers (14%) and doctors (11%). CONCLUSIONS: Climbing frequency and technical difficulty are associated with climbing injuries occurring at both indoor and outdoor venues, particularly cumulative trauma to the upper extremities.

The prevention of counterproductive or antisocial risk taking is a research priority. Attempts to understand risk-taking behaviors are dominated by the psychometric and neuropsychological paradigms, which have developed in relative isolation. Previous studies indicate that risk taking is associated with the sensation-seeking personality trait, although the relationship with impulsivity may be complex. Poor risk-related decision making is associated with lesions to the ventromedial prefrontal cortex. Further research is necessary to establish which forms of risk taking are associated with the 5-factor model of personality and may be influenced by ventromedial prefrontal cortex functioning. The relationship between risk-related decision making and personality traits is also discussed in order to provide a basis for future research adopting an integrated model of risk taking behavior.