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 (CMRO ) was measured using arterial spin labeling and T -relaxation under spin tagging MRI protocols. Accelerometry-based fatigability status during a fast-paced 400m walk was determined using the Pittsburgh Fatigability Index (PPFI, higher=worse). Confounders included skeletal muscle energetics, measured in vivo using spectroscopy and ex vivo using respirometry, cardiorespiratory fitness (VO peak), weight, medication count, and multimorbidity. Multivariable logistic regression models were used to estimate the association (odds ratio (OR)) of CMRO 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%]). CMRO was positively associated with PPFI>0 (age and sex adjusted OR=1.61, 95% CI: 1.06, 2.45, p=0.03); adjustment for confounders attenuated the association. The positive association of brain energetics and fatigability warrants further study in older adults.