Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study

J Acad Nutr Diet. 2015 Feb;115(2):231-241. doi: 10.1016/j.jand.2014.07.006. Epub 2014 Sep 8.


Background: 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.

Objective: 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.

Design: 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.

Participants/setting: 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.

Results: 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.

Conclusions: 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.

Keywords: Cognitive impairment; Dementia; Folic acid; Vitamin B-12; Vitamin B-6.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / prevention & control
  • Dementia / diagnosis
  • Dementia / epidemiology*
  • Dementia / prevention & control
  • Female
  • Folic Acid / administration & dosage*
  • Follow-Up Studies
  • Humans
  • Incidence
  • Longitudinal Studies
  • Middle Aged
  • Motor Activity
  • Proportional Hazards Models
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Socioeconomic Factors
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*


  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12