Homocysteine as a Risk Factor for Cognitive Impairment in a Stroke Sample: Preliminary Results from the Sydney Stroke Study

Abstract

It has been suggested that hyperhomocysteinemia, in addition to increasing the risk of stroke, may produce cognitive impairment independently of stroke. To determine if homocysteine levels were related to cognitive impairment that could not be accounted for by infarction, we examined stroke subjects (n = 91) soon after the stroke and performed detailed neuropsychological evaluations and MRI scans 3 months later. Control subjects (n = 17) were similarly assessed. Total homocysteine (tHcy) levels at baseline were significantly higher in the stroke sample, and had an inverse relationship with acute stage MMSE scores, which became stronger with higher tHcy levels, but not after accounting for other risk factors: B-12 and folate levels, and stroke volume. When the stroke patients were divided into two groups (cognitively impaired and unimpaired) on the basis of the 3-month data, the former group had significantly more subjects with tHcy levels >20 mu mol/I. Factor III from the analysis of the neuropsychological data, which was interpreted as a frontal-attentional factor, had a significant correlation with tHcy levels (r = 0.47, P < 0.001), and this correlation was significant after correction for age, folate levels, stroke volume, and white matter hyperintensity scores on MRI. Our findings suggest that hyperhomocysteinemia not only increases the risk of stroke but leads to greater cognitive impairment in stroke patients.