Background: Higher intake of folate and vitamins B6 (pyridoxine hydrochloride) and B12 (cyanocobalamin) may decrease the risk of Alzheimer disease (AD) through the lowering of homocysteine levels. Objective: To relate intake of folate and vitamins B6 and B12 to AD risk. Design and Patients: We followed up 965 persons 65 years or older without dementia at baseline for a mean±SD period of 6.1±3.3 person-years after the administration of a semiquantitative food frequency questionnaire. Total, dietary, and supplement intake of folate and vitamins B6 and B12 and kilocalorie intake were estimated from the questionnaire responses. We related energy-adjusted intake of folate and vitamins B 6 and B12 to incident AD using the Cox proportional hazards regression model. Main Outcome Measure: Incident AD. Results: We found 192 cases of incident AD. The highest quartile of total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex, education, ethnic group, the ε4 allele of apolipoprotein E, diabetes mellitus, hypertension, current smoking, heart disease, stroke, and vitamin B6 and B 12 levels. Vitamin B6 and B12 levels were not related to the risk of AD. Conclusions: Higher folate intake may decrease the risk of AD independent of other risk factors and levels of vitamins B 6 and B12. These results require confirmation with clinical trials.
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