Differential effects of COMT on gait and executive control in aging

Walking speed is associated with attention and executive control processes subserved by the prefrontal cortex. Because polymorphisms in catechol-O-methyltransferase (COMT) influence these cognitive processes we hypothesized that the same polymorphisms may influence gait velocity. We examined the associations between the Val¹⁵⁸Met polymorphism in COMT and gait velocity as well as attention and executive function. Participants were 278 non-demented older adults. The results revealed that methionine (Met)/valine (Val) was associated with faster gait velocity. This association can be explained by the putative role of the Val allele in regulating tonic dopamine release in the striatum. In contrast, Met/Met was associated with better attention and executive function. Stratification by gender revealed that the association between COMT genotype and gait was significant only in men. Conversely, the association between COMT genotype and attention and executive function was significant only in women. These findings suggest a differential effect in relating the Val¹⁵⁸Met polymorphism to gait and to cognitive function while supporting the previously described sexual dimorphism in the phenotypic expressions of COMT.