Abstract
Body mass index (BMI) is commonly used to assess obesity, but it fails to capture the complexities of regional adiposity, which can have varying effects on brain health. This study analyzed data from over 18,000 UK Biobank participants to investigate the relationship between regional adiposity, measured using dual-energy X-ray absorptiometry, and brain health, evaluated through multimodal brain imaging and cognitive tests. Adiposity in the arm, leg, trunk and visceral regions was differentially associated with brain morphology, functional connectivity and white-matter integrity in the sensorimotor, limbic, default mode and subcortical-cerebellar-brainstem systems. The aging of these four brain systems was indexed by brain age gap (BAG), with cortical-related BAGs (sensorimotor, limbic, default mode) mediating relationships between visceral adiposity and cognitive performance in reasoning, executive function, processing speed and memory. These results highlight the importance of considering regional adiposity, beyond BMI, in characterizing its associations with brain and cognitive aging.