Genetic markers of dopaminergic transmission predict performance for older males but not females

Mobility and memory declines with aging can limit independence. Several single-nucleotide polymorphisms have been associated with cognitive performance, but studies investigating motor function are scant. We examined 4 single-nucleotide polymorphisms involved in dopaminergic metabolism: BDNF (Val66Met), DRD3 (Ser9Gly), DBH (C>T), and COMT (Val158Met) for their relationship to motor and cognitive function in healthy older adults (n = 4605 and n = 7331) who participated in the U.S. Health and Retirement Study. Individuals with genotypes associated with reduced dopamine metabolism exhibited poorer balance and memory. We found the most pronounced effects in the oldest participants (aged 85+ years), supporting the notion that age-related declines in dopamine availability contribute to magnified genotype effects with advancing age. Moreover, males demonstrated stronger associations than did females between a number of beneficial dopamine alleles and cognitive scores, suggesting that sex differences in dopaminergic transmission interact with genotype to influence performance. These findings point to common genetic variants related to dopaminergic metabolism that characterizes individual differences in motor and cognitive function in older adults.