Nigrostriatal Dopaminergic Neurotransmission and Resilience to Peripheral Systemic Risk Factors for Gait Slowing upon Transition to Uneven Surfaces in Older Adult

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Abstract
Identifying mechanisms that compensate for slow gait speed in older adults is crucial. Dopaminergic neurotransmission curbs deleterious associations of cerebrovascular disease with gait, but whether it compensates for peripheral systemic risk factors (PSRF) for gait slowing has not been studied. In this cross-sectional study of community-dwelling older adults, we examined the relationship between nigrostriatal dopaminergic terminal integrity and gait speed in individuals with and without ≥1 PSRF for gait slowing: obesity, joint pain, or reduced muscle strength. The primary outcome was percent difference in gait speed (%DGS) on transition from even to uneven surface. Participants underwent dopaminergic imaging with dihydrotetrabenazine [ 11 C]DTBZ positron emission tomography. Among 197 individuals, (mean (SD) age 74.92 (4.53) years; 61.93% female; 90.86% White), 130 (65.99%) had ≥1 PSRF. Relationship between posterior putamen [ 11 C]DTBZ binding and %DGS was modified by PSRF; in those with ≥1 PSRF (but not in those with no PSRF), posterior putamen [ 11 C]DTBZ binding was associated with %DGS (β=0.198, p=0.03) independent of potential confounders. This cross-sectional study indicates that striatal dopaminergic neurotransmission may offer resilience to effects of PSRF on gait slowing.
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