Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates

Purpose: Declining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time. Methods: We examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities. Results: Higher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant. Conclusions: In this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.