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Updated: Aug 17, 2026

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
Homocysteine as a risk factor for cognitive impairment in stroke patients
Perminder S Sachdev1, Michael J Valenzuela, Henry Brodaty
1School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Sydney, Australia. p.sachdev@unsw.edu.au
Background:
Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment.
Methods:
We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B(12), creatinine and plasma fibrinogen levels were obtained.
Results:
tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B(12) and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T(2)-weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-to-brain ratios as measures of brain atrophy.
Conclusion:
This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment.
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