Homocysteine and the Brain in Midadult Life

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