Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals

R. Clarke*, D. Bennett, S. Parish, S. Lewington, M. Skeaff, S.J.P.M. Eussen, C. Lewerin, D.J. Stott, J. Armitage, G.J. Hankey, E. Lonn, J.D. Spence, P. Galan, L.C. de Groot, J. Halsey, A.D. Dangour, R. Collins, the B-Vitamin Treatment Trialists' Collaboration, F. Grodstein

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE) type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean SE: 0.054 0.004 and 0.036 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: 0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: 0.01; 95% CI: 0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: 0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.
Original languageEnglish
Pages (from-to)657-666
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Volume100
Issue number2
DOIs
Publication statusPublished - Aug 2014

Keywords

  • RANDOMIZED CONTROLLED-TRIAL
  • FOLIC-ACID SUPPLEMENTATION
  • PLACEBO-CONTROLLED TRIAL
  • ALZHEIMERS-DISEASE
  • OLDER-ADULTS
  • CARDIOVASCULAR-DISEASE
  • PLASMA HOMOCYSTEINE
  • STROKE PREVENTION
  • VASCULAR-DISEASE
  • DOUBLE-BLIND

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