Catechol-O-methyltransferase (COMT) polymorphism predicts rapid gait speed changes in healthy older adults.

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 0.05). 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.