Homocysteine and the Brain in Midadult Life

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Abstract
The relationship between homocysteine (HCY) and the brain has received much recent attention.1,2High HCY levels have long been recognized to increase the risk of vascular disease. A meta-analysis of 27 studies reported a summary odds ratio for cerebrovascular disease of 1.9 for every 0.68-mg/L (5 μmol/L) increment in total HCY level (tHcy),3 while another such analysis reported an odds ratio of 3.97 if the tHcy level was higher than the 95th percentile.4 The focus of these studies has been large-vessel atheroembolic disease. Homocysteine has also been implicated in small-vessel disease, with an increased risk of leukoaraiosis attributed to it,5,6but the evidence for this has been less consistent.7Homocysteine has, in addition, been suggested as a risk factor for brain atrophy in healthy subjects8 and alcoholics9 and has been proposed to increase the risk of Alzheimer disease.10,11