Life-course body shape trajectories and cerebral oxygen metabolism in community-dwelling older adults

Obesity and lifelong body-shape fluctuation are associated with late-life structural brain damage, suggesting the involvement of metabolic pathways. The cerebral metabolic rate of oxygen (CMRO₂) reflects hemodynamic and oxidative stress and precedes structural atrophy, but its role in adiposity-related brain change remains unclear. We examined whether current and life-course adiposity relate to CMRO₂ and to structural change. A total of 303 community-dwelling adults aged 50 years and older were included. Body shape was assessed using Body Mass Index (BMI) and Body Roundness Index (BRI). Global CMRO₂ was derived from TRUST and phase-contrast MRI. T1-weighted MPRAGE provided volumetry, and medial temporal atrophy (MTA) grading. General linear models estimated associations of BMI and BRI with CMRO₂, including age interactions. Age-stratified mediation tested CMRO₂ as a mediator of adiposity to MTA associations. Body-shape trajectories at ages 25, 40, 60, and current age were modeled and related to CMRO₂ and metabolism-related regions. Adiposity was associated with lower CMRO₂: with overweight (β = -1.12 μmol/100 g/min, 95%CI = (-1.96, -0.28)) and higher BRI (β = -1.31, 95%CI = (-2.36, -0.27)) showing stronger effects with advancing age. Among participants aged 70 years, CMRO₂ mediated the association between BMI and MTA (indirect β = 0.06, 95%CI = (0.01, 0.14)). Three adulthood body-shape patterns emerged, and CMRO₂ was lower in moderate increasing (β = -11.40; 95%CI = (-20.90, -1.90)) and high-rising (β =  - 12.23; 95%CI = (-23.56, -0.90)) groups. Metabolism-related regions were larger in higher-risk patterns, particularly the left hypothalamus. Greater and prolonged adiposity is linked to reduced CMRO₂ and related structural differences in older adults.