Abstract
IMPORTANCE: Adapting one's gait speed to external circumstances is critical for safe ambulation. Dopamine (DA), critical for adapting to increased task demands, predicts usual gait speed and may exert a greater role in complex tasks like rapid gait speed. OBJECTIVE: We hypothesized that a genotypic proxy indicator of greater prefrontal DA signaling would predict significantly faster rapid gait. DESIGN: Longitudinal cohort study over 8 years. SETTING: Community-dwelling adults with no baseline mobility disability. PARTICIPANTS: N = 2353 participants from the Health ABC Study. MEASUREMENTS: Repeated measures of walking speed (meters/sec) were obtained in response to: "walk as fast as possible… (rapid gait) or "walk at your usual pace (usual gait)." Catechol-O-methyltransferase (COMT) val158met polymorphism indicated DA signaling (val/val = higher metabolism, lower DA signaling; met/met = lower metabolism, higher DA signaling). RESULTS: Participants declined in rapid gait from 1.55 (SD = 0.33) to 1.35 m/s (SD = 0.34). Across the full follow-up period, the met/met genotype was associated with significantly greater rapid gait slowing. In mixed effect models, between-group differences were independent of covariates, and remained similar after adjustment for sensorimotor function, cognition, depressive symptoms, and energy. Follow-up analyses indicated the met/met genotype had a significantly faster rapid gait speed compared to the val/val genotype for the first 3 years (p < 0.01) but not years 4-8 (p > 0.05). CONCLUSION: Greater prefrontal DA measured with COMT polymorphism may facilitate short-term adaptation to rapid walking demands that are lost over time. Studies should examine whether these effects are long-term and the underlying mechanistic pathways.