Life-Course Clinical Obesity and Midlife White Matter Hyperintensity Burden

Obesity is associated with adverse cardiometabolic outcomes and may have a detrimental effect on the structural health of the brain. Most previous studies rely on cross-sectional, body mass index–based measures that fail to capture cumulative exposure or metabolic severity. The Lancet Commission has proposed a clinical obesity framework distinguishing excess adiposity with cardiometabolic dysfunction from preclinical obesity. This study examines whether cumulative clinical obesity across early adulthood is associated with midlife brain MRI markers of small vessel disease and brain atrophy.