Energetic Cost of Walking and Brain Atrophy in Mid-to-Late Life.

ABSTRACT

BACKGROUND: Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. METHODS: We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates. RESULTS: At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02). CONCLUSIONS: The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.