The association between physical activity and dementia in an elderly population: the Rotterdam Study.

Several studies have associated physical activity with the risk of dementia, but mostly did so during short follow-up. It remains unclear whether physical activity also affects dementia during longer follow-up. We examined the association between physical activity and risk of dementia during a follow-up period up to 14 years.

Plasma amyloid β, depression, and dementia in community-dwelling elderly.

Plasma amyloid β (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, a few clinical studies tested the cross-sectional association of Aβ levels with depression in elderly and showed incongruous findings. Hence, we tested the longitudinal association between Aβ levels and depressive symptoms in community-dwelling elderly.

Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 × 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association.

Retinopathy and risk of dementia: the Rotterdam Study.

Objective: To investigate the relation between retinopathy and the risk of dementia.

Methods: We investigated the associations between retinopathy and dementia and its subtypes Alzheimer disease (AD) and vascular dementia both cross-sectionally and prospectively in the Rotterdam Study, a large population-based cohort study. Digitized retinal images were available for 195 participants with prevalent dementia and 6,078 participants without dementia at baseline (1990-1993).

Genome-wide association study of vascular dementia.

Background And Purpose: Most studies investigating the genetics of dementia have focused on Alzheimer disease, but little is known about the genetics of vascular dementia. The aim of our study was to identify new loci associated with vascular dementia.

Methods: We performed a genome-wide association study in the Rotterdam Study, a large prospective population-based cohort study in the Netherlands.

Associations of serum cortisol with cognitive function and dementia: the Rotterdam Study.

Higher levels of cortisol have been observed in persons with cognitive decline and dementia. It is unknown whether these higher levels are a cause or a consequence of disease. We investigated whether morning levels of serum cortisol were associated with cognitive function, cognitive decline, and the risk of dementia and Alzheimer's disease in the Rotterdam Study, a large prospective population based cohort study.

Plasma clusterin and the risk of Alzheimer disease.

Context: Variants in the clusterin gene are associated with the risk of Alzheimer disease (AD) and clusterin levels have been found to be increased in brain and cerebrospinal fluid of patients with AD. Plasma clusterin was reported to be associated with brain atrophy, baseline disease severity, and rapid clinical progression in patients with AD.

Objective: To evaluate the potential of plasma clusterin as a biomarker of the presence, severity, and risk of AD.

Genome-wide analysis of genetic loci associated with Alzheimer disease.

Context: Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD).

Objectives: To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35,000 persons (8371 AD cases).

Design, Setting, And Participants: In stage 1, we identified strong genetic associations (P < 10(-3)) in a sample of 3006 AD cases and 14,642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS.