Increasing Body Mass Index at Midlife is Associated with Increased Cortical Thinning in Alzheimer's Disease-Vulnerable Regions

Higher body mass index (BMI) at midlife is associated with greater decreases in cognitive function at older age as well as increased Alzheimer's disease (AD) risk, compared to those with normal BMI. Here, we tested whether BMI at midlife was associated with cortical thinning in brain regions known to be affected in early AD. We examined a large sample (n=404) of midlife individuals (44-49 years) from the PATH population-based study. Individuals were scanned with magnetic resonance imaging (1.5T) on up to three occasions over eight years. Change in cortical thickness was modeled as a linear function of BMI and change in BMI longitudinally. Being obese was associated with thinner right frontal cortex at baseline (44-49 years). Across all individuals, increasing BMI over the 8-year study period was associated with increased cortical thinning in posterior cingulate bilaterally, as well as right lingual gyrus, anterior cingulate, and the peri-calcarine sulcus. Accelerated age-related cortical atrophy at midlife, particularly in posterior cingulate, is consistent with increased risk of AD in individuals with high BMI at this age. The findings suggest that management of body weight at midlife could reduce the risk of AD.