Sex-Specific Association of Lifetime Body Mass Index with Alzheimer’s Disease Neuroimaging Biomarkers

BACKGROUND: Although recent studies indicate that the relationship between body mass index (BMI) and Alzheimer’s disease (AD) may differ by both sex and age of BMI measurement, little information is available on sex- or age-specific associations between BMI and AD neuropathologies. OBJECTIVE: To examined whether sex-specific BMIs measured at different life-stages (in early adulthood, midlife, and late life) were associated with cerebral amyloid-β (Aβ) deposition and AD-signature region cortical thickness (AD-CT) in cognitively normal (CN) older adults. METHODS: A total of 212 CN subjects aged 60–90 years (females 108, males 104), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessments, [(11)C] Pittsburgh Compound B positron emission tomography, and brain magnetic resonance imaging. BMIs at different life stages were calculated. Multiple regression analyses were performed separately for either sex. RESULTS: In males, lower early adulthood or midlife BMI was associated with greater cerebral Aβ deposition, but late life BMI was not. Lower midlife BMI was associated with reduced AD-CT, but the BMI in early adulthood and late life was not. In females, no significant association was observed between any lifetime BMI and Aβ deposition or AD-CT. CONCLUSION: Our results support a male-specific association between BMI prior to late life, and in vivo AD pathologies. Avoiding underweight status early in life may be important to prevent AD dementia in males, but not females.