Overweight and Obesity in Midlife and Brain Structure and Dementia 26 Years Later: The AGES-Reykjavik Study

Abstract

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.

Keywords: brain MRI; brain vascular lesions; cohort study; dementia; epidemiology; mortality; obesity.

Figure 1.

Derivation of the analytic sample, the Age, Gene/Environment Susceptibility-Reykjavik Study, 1967–2006. BMI, body mass index; MRI, magnetic resonance imaging.

Figure 2.

Relative risks of dementia, brain infarcts, and brain microbleeds by midlife by body mass index (weight in kilograms divided by height in meters squared; BMI), the Age, Gene/Environment Susceptibility-Reykjavik Study, 1967–2006 (n = 3,864). Relative risks (on an arithmetic scale) for overweight (BMI of 25–29.9) and obese (BMI ≥30) participants were compared with those of normal-weight (BMI 18.5–24.9) participants using Poisson models that were adjusted for sex, age in midlife, number of follow-up years, presence of the Apolipoprotein ε4 allele, educational level, intracranial volume, physical activity level, systolic and diastolic blood pressures, and serum cholesterol level in midlife and for coronary artery calcium, prevalent coronary heart disease, hypertension, diabetes, depression, and drinking and smoking habits in late life. The models for dementia were further adjusted for brain infarcts and percentage of white matter lesion volume. Bars, 95% confidence intervals.

Figure 3.

Associations of midlife overweight, obesity, and normal weight with total brain volume and white matter lesion volume relative to intracranial volume, the Age, Gene/Environment Susceptibility-Reykjavik Study, 1967–2006 (n = 3,864). β coefficients represent the unit changes in percentage of total brain volume and percentage of white matter lesion volume for overweight (body mass index (weight (kg)/height (m)² of 25–29.9) and obese (body mass index ≥30) participants compared with normal weight (body mass index of 18.5–24.9) participants from multivariate linear regression models that were adjusted for sex, age in midlife, number of follow-up years, Apolipoprotein ε4 allele, educational level, intracranial volume, physical activity level, systolic and diastolic blood pressure, and serum cholesterol level in midlife and for coronary artery calcium, prevalent coronary heart disease, hypertension, diabetes, depression, and drinking and smoking status in late life. The models for percentage of total brain volume are further adjusted for infarct-like brain lesions. Bars, 95% confidence intervals.