Abstract

Objective: We aimed to verify the association between diabetes and the risk of dementia, Alzheimer disease (AD) and vascular dementia (VaD) in twins, and to explore whether genetic and early-life environmental factors could contribute to this association.

Research Design and Methods: This study included 13,693 twin individuals aged ≥65. Dementia was diagnosed according to DSM-IV criteria. Information on diabetes was collected from the inpatient registry, and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and 2) co-twin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression.

Results: Of all participants, 467 were diagnosed with dementia including 292 AD and 105 VaD cases, and 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16-2.36) for AD and 2.17 (1.36-3.47) for VaD. Compared to late-life diabetes (onset age ≥65), the risk effect of midlife diabetes (onset age <65) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30-1.53) for dementia related to mid- and late-life diabetes respectively.

Conclusions: Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at midlife than in late-life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association, but could not account for the midlife diabetes-dementia association.