Objective: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val 158 met) genotype and cognition in older adults.
Methods:We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined.
Results:Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: Ϫ2. Aging is commonly associated with decline in cognitive function, with the largest decline noted in prefrontal cortex (PFC)-dependent executive functioning. 1 Recent studies have reported that age-related loss of dopaminergic function correlates with cognitive impairment.2 Indeed, dopamine is necessary for PFC function and an imbalance of dopamine may produce deficits in PFC-dependent tasks, namely tasks of executive function. Met polymorphism, with the Val allele exhibiting a threefold to fourfold increase in enzyme activity compared to the Met allele.5 Several cross-sectional studies show that the Val/Val genotype is associated with less efficient cognitive processing and poorer performance on cognitive tests compared to the Met/