Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey

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Abstract
Background: High circulating total homocysteine (tHcy) concentrations are associated with stroke, which is a major cause of cognitive dysfunction. Blood homocysteine concentrations are inversely correlated with performance on some cognitive-function tests and a relation was recently shown between hyperhomocysteinemia and Alzheimer disease. Objective: The objective was to evaluate the relation between serum tHcy concentrations and performance on short delayed-recall tests of elderly men and women participating in the third National Health and Nutrition Examination Survey, phase 2 (1991–1994). Design: Subjects were aged ≥60 y. Subjects reported no previous stroke, completed ≥8 y of education, and took a test of delayed recall of story ideas (n = 1200) or words (n = 1270). Results: After adjustment for sex, age, race-ethnicity, income, years of education, and serum creatinine concentration, subjects in the upper half of the folate distribution recalled, on average, >4 of 6 story ideas; subjects with lower folate status recalled significantly fewer ideas (P < 0.001). Of the subjects with low folate status, story recall was significantly poorer in those with serum tHcy concentrations above the 80th percentile of the distribution (13.7 μmol/L) than in those with lower tHcy concentrations (P < 0.03). The odds ratio relating hyperhomocysteinemia to recall of ≥1 of 3 previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5 demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for serum folate concentration. Conclusion: Hyperhomocysteinemia is related to poor recall and this association was partially independent of folate status.