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José A. Luchsinger, MD; Ming-Xin Tang, PhD; Joshua Miller, PhD; Ralph Green, MD; Richard Mayeux, MD

Arch Neurol. 2007;64(1):86-92.

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 B₆ 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 4 allele of apolipoprotein E, diabetes mellitus, hypertension, current smoking, heart disease, stroke, and vitamin B₆ and B₁₂ 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 B₆ and B₁₂. These results require confirmation with clinical trials.

Author Affiliations: Taub Institute for Research of Alzheimer's Disease and the Aging Brain (Drs Luchsinger, Tang, and Mayeux), Divisions of Biostatistics (Dr Tang) and Epidemiology (Dr Mayeux), Joseph P. Mailman School of Public Health, and Gertrude H. Sergievsky Center (Dr Mayeaux), Columbia University, and Division of General Medicine, Department of Medicine (Dr Luchsinger) and Departments of Neurology and Psychiatry (Dr Mayeaux), Columbia University College of Physicians and Surgeons, New York, NY; and Department of Medical Pathology, School of Medicine, University of California–Davis (Drs Miller and Green).

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