Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women’s Health Initiative Memory Study
Open accessAbstract
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.
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Low folate status is associated with higher risk of cognitive decline or dementia.
“Additional evidence comes from longitudinal studies, such as in a prospective cohort that enrolled more than 7000 women aged 65–79 years: low baseline folate intakes (i.e., below the recommended 400 µg/day) or low serum folate concentrations were significantly associated with a higher risk of cognitive decline or dementia during a 5 year follow-up [163].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [163]
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- Authors
- Agnew-Blais, J. C., Wassertheil-Smoller, S., Kang, J. H., Hogan, P. E., Coker, L. H., Snetselaar, L. G., & Smoller, J. W.
- Affiliations
- Albert Einstein College of Medicine (US)
- Brigham and Women's Hospital (US)
- Wake Forest University Health Sciences (US)
- Wake Forest University (US)
- University of Iowa (US)
- Massachusetts General Hospital (US)
- Venue
- Journal of the Academy of Nutrition and Dietetics
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 115
- Issue
- 2
- Pages
- 231-241
- ISSN
- 2212-2672 (ISSN-L)
- PMC
- PMC4312724
- OpenAlex
- W1986973618
- Cited by
- 95
- References
- 75
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 10 · 2018: 12 · 2017: 6 · 2016: 8 · 2015: 6
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the Academy of Nutrition and Dietetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services (HHSN268201100002C, HHSN2682011 00003C, HHSN 268201100001C, HHSN268201100046C, HHSN268201100004C, HHSN-271-2011-00004C)
- Brigham and Women's Hospital
- Ohio State University
- Wake Forest University
- University of Pittsburgh
- MedStar Health Research Institute
- National Institutes of Health (HHSN268201100004C, N01 WH 44221, HHSN268201100046C, HHSN271201100004C, HHSN268201100001C, n01wh42119-25-0-1, HHSN268201100002C, HHSN268201100003C, N01 WH042119)
- University at Buffalo
- National Institute on Aging (N01-AG-9-2115)
- National Heart, Lung, and Blood Institute (HHSN268201100004C, HHSN271201100004C, HHSN26820-1100002C, HHSN268201100046C, HHSN268201100001C, HHSN268201100003C)
- National Institute of Mental Health (T32MH017119, K24MH094614)
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- folate intake, vitamin B6, vitamin B12, mild cognitive impairment, dementia, postmenopausal women, cognitive decline, dietary intake, folic acid supplementation, Women's Health Initiative Memory Study
- MeSH terms
- Aged, Dementia, Female, Folic Acid, Follow-Up Studies, Humans, Longitudinal Studies, Middle Aged, Motor Activity, Prospective Studies, Socioeconomic Factors, Vitamin B 12, Incidence, Proportional Hazards Models, Randomized Controlled Trials as Topic, Treatment Outcome, Vitamin B 6, Cognitive Dysfunction
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