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Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID).
Biochim Biophys Acta. 2016 05; 1862(5):1008-17.BB

Abstract

Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10μM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200μM), mild-moderate hyperhomocysteinemia ([HCy]: 10-100μM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100μM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support HCy as a mediator for VCID. In our view further trials of combined B-vitamin supplementation are called for, incorporating lessons from previous trials and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; and target cohorts with low baseline B-vitamin status. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Authors+Show Affiliations

Cardiovascular and Cell Sciences Research Centre, St Georges University of London, London SW17 0RE, UK. Electronic address: ahainsworth@sgul.ac.uk.Cardiovascular and Cell Sciences Research Centre, St Georges University of London, London SW17 0RE, UK.Sanders-Brown Center on Aging, University of Kentucky, Lexington KY 40536, USA.Sanders-Brown Center on Aging, University of Kentucky, Lexington KY 40536, USA. Electronic address: donna.wilcock@uky.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26689889

Citation

Hainsworth, Atticus H., et al. "Homocysteine, Hyperhomocysteinemia and Vascular Contributions to Cognitive Impairment and Dementia (VCID)." Biochimica Et Biophysica Acta, vol. 1862, no. 5, 2016, pp. 1008-17.
Hainsworth AH, Yeo NE, Weekman EM, et al. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). Biochim Biophys Acta. 2016;1862(5):1008-17.
Hainsworth, A. H., Yeo, N. E., Weekman, E. M., & Wilcock, D. M. (2016). Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). Biochimica Et Biophysica Acta, 1862(5), 1008-17. https://doi.org/10.1016/j.bbadis.2015.11.015
Hainsworth AH, et al. Homocysteine, Hyperhomocysteinemia and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Biochim Biophys Acta. 2016;1862(5):1008-17. PubMed PMID: 26689889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). AU - Hainsworth,Atticus H, AU - Yeo,Natalie E, AU - Weekman,Erica M, AU - Wilcock,Donna M, Y1 - 2015/12/09/ PY - 2015/09/18/received PY - 2015/11/27/revised PY - 2015/11/29/accepted PY - 2015/12/23/entrez PY - 2015/12/23/pubmed PY - 2019/1/25/medline KW - Brain KW - Dementia KW - Homocysteine KW - Hyperhomocysteinemia KW - Vascular cognitive impairment SP - 1008 EP - 17 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1862 IS - 5 N2 - Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10μM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200μM), mild-moderate hyperhomocysteinemia ([HCy]: 10-100μM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100μM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support HCy as a mediator for VCID. In our view further trials of combined B-vitamin supplementation are called for, incorporating lessons from previous trials and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; and target cohorts with low baseline B-vitamin status. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/26689889/Homocysteine_hyperhomocysteinemia_and_vascular_contributions_to_cognitive_impairment_and_dementia__VCID__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(15)00362-2 DB - PRIME DP - Unbound Medicine ER -