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Updated: Aug 5, 2026

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
07:30

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

Published on: April 23, 2021

Hyperhomocysteinemia and the risk of silent brain infarcts: systematic review and meta-analysis

Mahmoud Afia1, Alaa Abdelraheam2, Sai Krishna Vallamchetla1

  • 1Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
|July 30, 2026
PubMed

Insights

Hyperhomocysteinemia, a condition of high homocysteine levels, is linked to a greater risk of silent brain infarcts. This condition also shows a trend toward lower cognitive performance, suggesting homocysteine may be a target for intervention.

Area of Science:

  • Neurology
  • Cardiovascular Science
  • Metabolic Research

Background:

  • Elevated homocysteine levels (hyperhomocysteinemia) have been observed in patients with silent brain infarction.
  • Limited evidence exists comparing silent brain infarct rates based on hyperhomocysteinemia status.

Purpose of the Study:

  • To conduct a systematic review and meta-analysis.
  • To compare silent brain infarct rates in patients with hyperhomocysteinemia versus normal homocysteine levels.

Main Methods:

  • Systematic literature search up to June 17, 2025.
  • Included observational studies comparing image-confirmed silent brain infarct rates.
  • Calculated pooled odds ratios (OR) with 95% confidence intervals (CI) using random-effects model.
  • Performed subgroup analyses based on hyperhomocysteinemia cutoffs (>12 µmol/L and 9-12 µmol/L).

Main Results:

  • Four studies with 2331 patients were analyzed.
  • Silent brain infarct rate was 23.4% in hyperhomocysteinemia vs. 22.8% in controls (OR 1.84; P=0.02).
  • Association was stronger with higher homocysteine cutoffs (>12 µmol/L; OR 3.08).
  • Cognitive performance (MMSE) was numerically lower but not significantly different between groups.

Conclusions:

  • Hyperhomocysteinemia is associated with an increased risk of silent brain infarcts.
  • Cognitive performance may be numerically lower in individuals with hyperhomocysteinemia.
  • Higher homocysteine levels may correlate with a stronger association with silent brain infarction.
  • Further prospective studies are needed to explore homocysteine as a therapeutic target.
Abstract

Keywords:
Cerebral small vessel diseaseCognitive impairmentHomocysteineHyperhomocysteinemiaSilent brain infarcts

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