Homocysteine and cognition: A systematic review of 111 studies

Neurosci Biobehav Rev. 2016 Oct;69:280-98. doi: 10.1016/j.neubiorev.2016.08.014. Epub 2016 Aug 13.


Background: Elevated plasma homocysteine ​​(Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected.

Methods: We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed.

Results: We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline.

Discussion: Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.

Keywords: Cognition; Cognitive domains; Cognitive impairment; Hyperhomocisteinemia; Plasma Hcy.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Cognition Disorders
  • Cognition*
  • Cross-Sectional Studies
  • Folic Acid
  • Homocysteine
  • Humans
  • Vitamin B 12


  • Homocysteine
  • Folic Acid
  • Vitamin B 12