COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

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: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]).

CONCLUSION

These findings suggest that the Val allele has a protective impact on cognitive decline in late life.