Cerebral Metabolic Rate of Oxygen and Accelerometry-Based Fatigability in Community-Dwelling Older Adults

Alterations in energy metabolism may drive fatigue in older age, but prior research primarily focused on skeletal muscle energetics without assessing other systems and utilized self-reported measures of fatigue. We tested the association between energy metabolism in the brain and an objective measure of fatigability in the Study of Muscle, Mobility and Aging (N = 119, age 76.8 ± 4.0 years, 59.7% women). Total brain cerebral metabolic rate of oxygen (CMRO₂) was measured using arterial spin labeling and T₂-relaxation under spin tagging MRI protocols. Accelerometry-based fatigability status during a fast-paced 400 m walk was determined using the Pittsburgh Performance Fatigability Index (PPFI, higher = worse). Confounders included skeletal muscle energetics, measured in vivo using spectroscopy and ex vivo using respirometry, cardiorespiratory fitness (VO₂peak), weight, medication count, and multimorbidity. Multivariable logistic regression models were used to estimate the association (odds ratio (OR)) of CMRO₂ with PPFI > 0 compared to the referent group PPFI = 0. Models were first adjusted for age and sex and further adjusted for confounders. In this sample, 41.2% had PPFI > 0 (median 3.3% [0.4%-8.0%]). Higher CMRO₂ was associated with exhibiting performance fatigability (age- and sex-adjusted OR = 1.61, 95% CI: 1.06, 2.45, p = 0.03). This association remained significant after adjusting for in vivo skeletal muscle energetics and VO₂peak, suggesting that performance fatigability is associated with multi-system impairments in older adults.