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Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality.
Nutr Rev 2015; 73(10):723-35NR

Abstract

Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed.

Authors+Show Affiliations

A. McCaddon is with the School of Medicine, Cardiff University, Cardiff, United Kingdom. J.W. Miller is with the School of Environmental and Biological Sciences, Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey, United States.A. McCaddon is with the School of Medicine, Cardiff University, Cardiff, United Kingdom. J.W. Miller is with the School of Environmental and Biological Sciences, Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey, United States. jwmiller@aesop.rutgers.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26293664

Citation

McCaddon, Andrew, and Joshua W. Miller. "Assessing the Association Between Homocysteine and Cognition: Reflections On Bradford Hill, Meta-analyses, and Causality." Nutrition Reviews, vol. 73, no. 10, 2015, pp. 723-35.
McCaddon A, Miller JW. Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality. Nutr Rev. 2015;73(10):723-35.
McCaddon, A., & Miller, J. W. (2015). Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality. Nutrition Reviews, 73(10), pp. 723-35. doi:10.1093/nutrit/nuv022.
McCaddon A, Miller JW. Assessing the Association Between Homocysteine and Cognition: Reflections On Bradford Hill, Meta-analyses, and Causality. Nutr Rev. 2015;73(10):723-35. PubMed PMID: 26293664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality. AU - McCaddon,Andrew, AU - Miller,Joshua W, Y1 - 2015/08/18/ PY - 2015/8/22/entrez PY - 2015/8/22/pubmed PY - 2016/4/19/medline KW - B vitamins KW - causality KW - cognition KW - dementia KW - homocysteine SP - 723 EP - 35 JF - Nutrition reviews JO - Nutr. Rev. VL - 73 IS - 10 N2 - Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed. SN - 1753-4887 UR - https://www.unboundmedicine.com/medline/citation/26293664/Assessing_the_association_between_homocysteine_and_cognition:_reflections_on_Bradford_Hill_meta_analyses_and_causality_ L2 - https://academic.oup.com/nutritionreviews/article-lookup/doi/10.1093/nutrit/nuv022 DB - PRIME DP - Unbound Medicine ER -