Homocysteine and cognitive function in a population-based study of older adults

OBJECTIVES: To assess the relations between homocysteine levels and neurobehavioral test scores representing a broad range of cognitive domains in a population-based study of older adults. DESIGN: Cross-sectional analysis of first-visit data of subjects in the Baltimore Memory Study, a longitudinal study. SETTING: Specific neighborhoods in Baltimore. PARTICIPANTS: Participants were 1,140 randomly selected residents aged 50 to 70 with a mean age ± standard deviation of 59.3 ± 5.9; 65.9% were female, and 54.2% were white and 41.1% African-American. MEASUREMENTS: Twenty neurobehavioral test scores in eight cognitive domains. RESULTS: Linear regression models revealed that homocysteine was consistently and strongly associated with worse neurobehavioral test performance, in crude analysis and after control for a large set of important covariates. Associations were observed in all eight cognitive domains assessed but were strongest and most consistent in the domains of simple motor and psychomotor speed, eye-hand coordination/manual dexterity, and verbal memory and learning. On average, an increase in homocysteine levels from the 25th to the 75th percentile, all in the generally accepted normal range, was equivalent in its association with neurobehavioral test scores to an increase of 4.2 years of age. Logistic regression models revealed that, on average, for the neurobehavioral tests associated with homocysteine, subjects in the highest quartile of homocysteine levels were more than two times as likely to be in the lowest quartile of neurobehavioral test scores as those in the lowest quartile. CONCLUSION: Higher homocysteine levels were associated with worse function across a broad range of cognitive domains, and the magnitude of the associations was large. The data suggest that homocysteine may be a potentially important modifiable cause of cognitive dysfunction.