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Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts.Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample).Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. [ABSTRACT FROM AUTHOR]

Objective: Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.Research Design and Methods: This was a prospective cohort study of 4,446 men and women aged 65-91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score ≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.Results: After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02-2.95) odds for new-onset depressive symptoms in the youngest age-group (65-70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.Conclusions: Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65-70 years. [ABSTRACT FROM AUTHOR]

The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 (‘normal’, n = 8,689), 24-27 (‘mild dysfunction’, n = 2,231) and <24 (‘severe dysfunction’, n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis . Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11–1.46 and 1.42, 95% CI 1.01–1.99; both p < 0.05), cardiovascular death (1.41, 95% CI 1.16–1.71 and 1.56, 95% CI 0.99–2.46; both p ≤ 0.05) and all-cause death (1.33, 95% CI 1.16–1.54 and 1.50, 95% CI 1.06–2.12; both p < 0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14–3.87; p = 0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline. Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events. ClinicalTrials.gov NCT00145925 Supported by grants from Servier and from the National Health and Medical Research Council of Australia. [ABSTRACT FROM AUTHOR]

White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Increases in longevity will involve a significant increase among the number of drivers in the very old, who are at greater risk of being involved in road accidents. Data are thus needed from studies of older populations to characterize those still driving, the reasons for giving up and to help formulate appropriate policies for dealing with the problems faced and created by an increase in older drivers.Methods: A driving questionnaire was administered to surviving members of a cohort comprising a representative sample of individuals aged >/=84, the Cambridge City over 75 Cohort. Out of 546 survivors 404 completed the driving questionnaire at the 9-year follow-up. In addition, subjects were assessed, at baseline and at each follow-up, for cognitive performance using the Mini-Mental State Examination (MMSE) and for physical impairment using the Instrumental of Activities in Daily Living (IADL) scale.Results: Of the sample, 37% had driven in the past, and 8.4% were still driving, the majority regularly. The drivers tended to be younger (mean age 86.6 years), men (71%) and to be married (67.7%). Although physical disability and cognitive impairment are common in this age group, current drivers had few physical limitations on their daily activities and were not impaired on MMSE. None of the current drivers had visual impairment and 22.6% had hearing loss. Of those who had given up driving, 48.5% had given up at the age of >/=80. The commonest reasons for giving up driving were health problems (28.6%), and loss of confidence (17.9%). One-third reported giving up driving on advice.Conclusion: A process of self-selection takes place among older drivers. People over the age of 84 who are still driving have generally high levels of physical fitness and mental functioning, although some have some sensory loss. Given the likely increase in the number of older drivers over the next decades, safety will be improved most by strategies aimed at the entire driving population with older drivers in mind, rather than relying on costly screening programmes to identify the relatively small numbers of impaired older people who continue to drive. [ABSTRACT FROM AUTHOR]

Heavy alcohol drinking is associated with cognitive impairment, but little is known concerning the cognitive effect of moderate alcohol consumption. The Epidemiology of Vascular Aging (EVA) Study is a longitudinal study of cognitive and vascular aging. Between June 1991 and June 1993, 1,389 subjects aged 59-71 years (574 men and 815 women) who had been recruited from the electoral rolls of Nantes, France, were examined. Trained psychologists administered a battery of 10 neuropsychological tests assessing most areas of cognitive functioning. Detailed information on alcohol intake was collected during a structured interview. A multiple linear regression model was used to examine the relations between test scores and alcohol consumption at baseline in men and women separately, controlling for age, education, income, depressive symptoms, and smoking status. Odds ratios for being a high cognitive performer (i.e., being in the top 10% of the distribution of summary scores from the neuropsychological battery) were calculated. Among men, neuropsychological test scores were not associated with alcohol consumption in either univariate or multivariate analysis; nor did the proportion of high cognitive performers vary by alcohol consumption. In contrast, among women, significant positive associations between alcohol consumption and cognitive performance were observed for most tests in multivariate analysis. For example, for the Mini-Mental State Examination, the adjusted mean score for female nondrinkers was 27.5 and that for the heaviest drinkers 28.2 (p < 0.001). The odds ratio for being a high cognitive performer was 2.5 (95% confidence interval 1.1-5.7) for women who usually consumed two or more drinks per day in comparison with nondrinkers. These findings suggest that, among women, moderate alcohol consumption may have a beneficial effect on cognitive function. [ABSTRACT FROM AUTHOR]