Visceral fat is associated with lower brain volume in healthy middle-aged adults

Objective: Midlife obesity has been associated with an increased risk of dementia. The underlying mechanisms are poorly understood. Our aim was to examine the cross-sectional association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic resonance imaging (MRI) markers of brain aging in middle-aged community adults. Methods: Participants from the Framingham Offspring cohort were eligible if in addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone a volumetric brain MRI scan with measurements of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts (BI). All analyses were adjusted for age, sex, and time interval between abdominal CT and brain MRI. Results: In a sample of 733 community participants (mean age, 60 years; 53% women), we observed an inverse association of BMI (estimate by standard deviation unit ± standard error = -0.27 ± 0.12; p = 0.02), WC (-0.30 ± 0.12; p = 0.01), WHR (-0.37 ± 0.12; p = 0.02), SAT (-0.23 ± 0.11; p = 0.04), and VAT (-0.36 ± 0.12; p = 0.002) with TCBV, independent of vascular risk factors. The association between VAT and TCBV was the strongest and most robust, and was also independent of BMI (-0.35 ± 0.15; p = 0.02) and insulin resistance (-0.32 ± 0.13; p = 0.01). When adjusting for C-reactive protein levels, the associations were attenuated (-0.17 ± 0.13; p = 0.17 for VAT). No consistently significant association was observed between the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI. Interpretation: In middle-aged community participants, we observed a significant inverse association of anthropometric and CT-based measurements of abdominal, especially visceral, fat with total brain volume.