Overweight and Obesity in Midlife and Brain Structure and Dementia 26 Years Later

High adiposity in midlife might increase risk for late-life brain pathology, including dementia. Using data from the prospective Age, Gene/Environment Susceptibility-Reykjavik Study of men and women (born 1907-1935), we studied the associations of overweight and obesity at midlife (mean age, 50 (standard deviation, 4.7) years) with 1.5-T brain magnetic resonance imaging measures of infarct-like brain lesions, cerebral microbleeds, total brain volume, and white matter lesions volume, as well as dementia, in late life (mean age, 76 (standard deviation, 5.2) years). We used linear and Poisson models to estimate associations in 3,864 persons after adjustment for sociodemographic, health, and lifestyle characteristics. In midlife, the prevalence of overweight was 39% and that of obesity was 8%. After a mean follow-up of 26.2 (standard deviation, 4.9) years, midlife overweight and obesity were not associated with infarct-like brain lesions (relative risk (RR) = 0.82, 95% confidence interval (CI): 0.61, 1.10), cerebral microbleeds (RR = 0.69, 95% CI: 0.37, 1.32), total brain volume (β = 0.05, 95% CI: -0.34, 0.45), white matter lesions volume (β = -0.10, 95% CI: -0.20, 0.01), or dementia (RR = 0.91, 95% CI: 0.49, 1.72) compared with normal weight. These findings do not support the hypothesis that high body mass index in midlife modulates the risk for dementia.