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

Abstract

Background Whether higher B vitamin (B6, B12, and folate) intake 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, observe no effect on cognition. We examine 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 B6 and/or B12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women. Design Prospective, longitudinal cohort study. B vitamin intake was self-reported using a food frequency questionnaire administered at baseline between May 1996 and December 1999. 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 RDA at study baseline was associated with increased risk of incident MCI/probable dementia (HR=2.0, 95% CI: 1.3, 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B6 or B12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake. Conclusions Folate intake below the RDA 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.

Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians

“…Many clinical trials investigating HCY reduction as a potential modifiable risk factor employed vitamin B6, B12, and folic acid (B9) to reduce HCY although the clinical benefit is still under debate [81-84]. The inconsistent results of clinical trials may partly be due to unexplained genetic factors influencing HCY.…”

Authors’ reply to Smith and colleagues

“…This suggests that food fortification could reduce the long term risk of cognitive impairment. 17 As has been stated previously, the phenomenon that Smith and colleagues report is probably the result of people who have untreated vitamin B 12 deficiency taking multivitamin supplements. 18 19 Such people would absorb the folic acid, resulting in high folate concentrations, but would not absorb the vitamin B 12 .…”

Cognitive decline: A vitamin B perspective

“…Similarly, in the HAPIEE (health, alcohol and psychosocial factors in Eastern Europe) study comprising 4,166 participants, folate and vitamin B12 were positively associated with performance (verbal fluency, immediate recall) [41]. In addition, in 7,030 postmenopausal women without memory cognitive impairment or probable dementia, monitored for over 5 years, those with folate intake below the recommended daily allowance were associated with increased risk of mild cognitive impairment and probable dementia [42]. Conversely, a 2 year folic acid and vitamin B12 supplementation study in 2,919 individuals over 65 years of age with high homocysteine levels, showed no beneficial effects on performance on 4 cognitive domains, although a small improvement in global cognition was noted [43].…”