Hyperhomocysteinemia as a Risk Factor for Vascular Contributions to Cognitive Impairment and Dementia

Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, preclinical and clinical data shows it is not. Clinical trials using B vitamin supplementation have shown conflicting results about the benefits of lowering homocysteine and issues have arisen over proper study design within the trials. Studies using cell culture and animal models have proposed several mechanisms for homocysteine-induced cognitive decline, providing other targets for therapeutics. For this review, we will focus on HHcy as a risk factor for VCID, specifically, the different mechanisms proposed for homocysteine-induced cognitive decline and the clinical trials aimed at lowering plasma homocysteine.

Original languageEnglish
Article number350
JournalFrontiers in Aging Neuroscience
StatePublished - Oct 31 2018

Bibliographical note

Funding Information:
Funding. This work was supported by National Institutes of Health grants RO1NS079637 and RO1NS097722 to DW, and fellowship F31NS092202 to EW. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© Copyright © 2018 Price, Wilcock and Weekman.


  • B vitamins
  • dementia
  • homocysteine
  • hyperhomocysteinemia
  • vascular cognitive impairment and dementia

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience


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