Hainsworth, AH; Yeo, NE; Weekman, EM; Wilcock, DM
(2016)
Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID).
BBA - Molecular Basis of Disease, 1862 (5).
pp. 1008-1017.
ISSN 0925-4439
https://doi.org/10.1016/j.bbadis.2015.11.015
SGUL Authors: Hainsworth, Atticus Henry Yeo, Natalie Emma
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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.
Item Type: | Article | |||||||||||||||
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Additional Information: | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||||||||
Keywords: | Brain, Dementia, Homocysteine, Hyperhomocysteinemia, Vascular cognitive impairment, Homocysteine, Dementia, Brain, Vascular cognitive impairment, Hyperhomocysteinemia, Biochemistry & Molecular Biology, 06 Biological Sciences, 02 Physical Sciences, 0601 Biochemistry And Cell Biology, 1101 Medical Biochemistry And Metabolomics, 1103 Clinical Sciences | |||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical & Biomedical Education (IMBE) Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE ) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
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Journal or Publication Title: | BBA - Molecular Basis of Disease | |||||||||||||||
ISSN: | 0925-4439 | |||||||||||||||
Language: | eng | |||||||||||||||
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Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | |||||||||||||||
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PubMed ID: | 26689889 | |||||||||||||||
Web of Science ID: | WOS:000374609200018 | |||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/107573 | |||||||||||||||
Publisher's version: | https://doi.org/10.1016/j.bbadis.2015.11.015 |
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