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Folate, Vitamin B-6, and Vitamin B-12 Intake and Mild Cognitive Impairment and Probable Dementia in the Women’s Health Initiative Memory Study

Published:September 08, 2014DOI:



      Whether higher B vitamin intake (ie, B-6, B-12, and folate) is protective against cognitive decline in later life remains uncertain. Several prospective, observational studies find higher B vitamin intake to be associated with lower risk of dementia; other studies, including most trials of B vitamin supplementation, have observed no effect on cognition. We examined this question in a large population of older women carefully monitored for development of mild cognitive impairment (MCI) and probable dementia.


      To determine whether baseline folate, vitamin B-6, and/or vitamin B-12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women.


      Prospective, longitudinal cohort study. Participants were enrolled between 1993 and 1998, and B vitamin intake was self-reported using a food frequency questionnaire administered at baseline.


      Postmenopausal women (N=7,030) free of MCI/probable dementia at baseline in the Women’s Health Initiative Memory Study.

      Main outcome measures

      Over a mean follow-up of 5.0 years, 238 cases of incident MCI and 69 cases of probable dementia were identified through rigorous screening and expert adjudication.

      Statistical analyses

      Cox proportional hazard models adjusting for sociodemographic and lifestyle factors examined the association of B vitamin intake above and below the Recommended Daily Allowance and incident MCI/probable dementia.


      Folate intake below the Recommended Daily Allowance at study baseline was associated with increased risk of incident MCI/probable dementia (hazard ratio 2.0, 95% CI 1.3 to 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B-6 or B-12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake.


      Folate intake below the Recommended Daily Allowance may increase risk for MCI/probable dementia in later life. Future research should include long-term trials of folic acid supplementation to examine whether folate may impart a protective effect on cognition in later life.


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      J. C. Agnew-Blais is an epidemiology merit fellow, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY.


      S. Wassertheil-Smoller is a distinguished university professor emerita, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY.


      J. H. Kang is an assistant professor of medicine, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.


      P. E. Hogan is a senior biostatistician, Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.


      L. H. Coker is an associate professor, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.


      L. G. Snetselaar is an endowed chair, professor, Department of Epidemiology, University of Iowa, Iowa City.


      J. W. Smoller is a professor and director of the Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston.