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

. 2014 Aug;100(2):657-66.

doi: 10.3945/ajcn.113.076349. Epub 2014 Jun 25.

Derrick Bennett 1, Sarah Parish 1, Sarah Lewington 1, Murray Skeaff 1, Simone J P M Eussen 1, Catharina Lewerin 1, David J Stott 1, Jane Armitage 1, Graeme J Hankey 1, Eva Lonn 1, J David Spence 1, Pilar Galan 1, Lisette C de Groot 1, Jim Halsey 1, Alan D Dangour 1, Rory Collins 1, Francine Grodstein 1; B-Vitamin Treatment Trialists’ Collaboration

Affiliations

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

Robert Clarke et al. Am J Clin Nutr. 2014 Aug.

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.

PubMed Disclaimer

Figures

FIGURE 1.

FIGURE 1.

Effects of B vitamins on specific domains of cognitive function and on a domain-composite score by using change from baseline in the cognitive-domain trials. The z scores for individual trials and the total for the cognitive-domain trials are shown separately for memory, speed, and executive function and for a domain-composite global cognitive function score. Black squares represent z score differences for the individual trials and the horizontal lines represent 95% CIs. The size of the squares is inversely proportional to the variance. Diamonds represent the z scores and 95% CIs for all trials.

FIGURE 2.

FIGURE 2.

Effects of B vitamins on MMSE-type global cognitive function score at the end of the treatment period in the global cognition trials. The z score for differences and their 95% CIs for MMSE-type global cognitive function scores are shown for individual trials and as the total for all trials. The z score differences are for B-vitamins compared with placebo. * refers to B-vitamin based treatment vs placebo. HOPE-2, Heart Outcomes Prevention Evaluation-2; MMSE, Mini-Mental State Examination; SEARCH, Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine; SU.FOL.OM3, Supplementation with Folate, vitamin B6 and B12 and/or Omega-3 fatty acids; VISP, Vitamin Intervention for Stroke Prevention; VITATOPS, Vitamins to Prevent Stroke; WAFACS, Women's Antioxidant and Folic Acid Cardiovascular Study.

FIGURE 3.

FIGURE 3.

Effects of B vitamins on cognitive aging in all available trials per year at a 25% reduction in homocysteine. The z score differences and their 95% CIs are provided for the domain-composite global cognitive function score in each cognitive-domain trial and for the MMSE-type global cognitive function score in the other trials. The years of cognitive aging equivalent and their 95% CIs are also provided for individual trials and their totals. The years of cognitive aging equivalent were determined on the basis of a 0.054/y reduction in the cognitive domain trial score and a 0.036/y reduction in the global cognition trial score. * indicates that the age association was based on 0.054 per year reduction in domain-composite z score for cognitive-domain trials and on 0.036 per year reduction in MMSE-type cognitive z score. FACIT, Folic Acid and Carotid Intima-Media Thickness; HOPE-2, Heart Outcomes Prevention Evaluation-2; MMSE, Mini-Mental State Examination; SEARCH, Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine; SU.FOL.OM3, Supplementation with Folate, vitamin B6 and B12 and/or Omega-3 fatty acids; tHcy, total homocysteine; VISP, Vitamin Intervention for Stroke Prevention; VITATOPS, Vitamins to Prevent Stroke; WAFACS, Women's Antioxidant and Folic Acid Cardiovascular Study.

Comment in

Similar articles

Cited by

References

    1. Mayeux R. Early Alzehimer's disease. N Engl J Med 2010;362:2194–201. - PubMed
    1. Clarke R, Smith AD, Jobst K, Sutton L, Refsum H, Ueland PM. Plasma homocysteine, folate and vitamin B-12 as risk factors for confirmed Alzheimer's disease. Arch Neurol 1998;55:1449–55. - PubMed
    1. Clarke R. B-vitamins and prevention of dementia. Proc Nutr Soc 2008;67:75–81. - PubMed
    1. Clarke R, Birks J, Nexo E, Ueland PM, Schneede PM, Scott J, Molloy A, Frost C, Evans JM. Low vitamin B12 status and risk of cognitive decline in older people. Am J Clin Nutr 2007;86:1384–91. - PubMed
    1. Seshadri S, Beiser A, Selhub J, Jacques P, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476–83. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources