Association Between Body Mass Index and Brain Aging in Adults: A 16-Year Population-Based Cohort and Mendelian Randomization Study

Motivation: The causal relationship between BMI and brain health remains unclear. Goal(s): This study aimed to demonstrate the effect of cumulative BMI on neuroimaging features in adults of different ages and verify the causal relationship. Approach: This study was based on the KaiLuan Study that began in 2006. We also performed two-sample Mendelian randomization analysis using genetic data from 681,275 individuals. Results: For adults aged under 45 years but BMI > 26.2 kg/m2 corresponded to 12.0 years of brain aging. Genetic analysis indicated causal relationships among high BMI, smaller volume of the cerebral parenchyma, and higher fractional anisotropy in projection fibers. Impact: High BMI is causally associated with smaller brain volume and abnormal microstructural integrity in projection fibers, especially in young adults. These findings provide a basis for future brain health promotion and disease prevention strategies.