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<p>India’s rapidly growing population is expected to face a substantial rise in cognitive impairment and dementia. Due to limited efficacy of existing treatment options, preventive strategies targeting modifiable risk factors are essential. One such factor is homocysteine, elevated levels of which have been studied as a modifiable vasculo-metabolic risk factor associated with cognitive impairment. This systematic review and meta-analysis aimed to synthesise current evidence on the relationship between homocysteine levels and cognition across cognitively unimpaired individuals, individuals with mild cognitive impairment and dementia in India. A systematic review and meta-analysis was registered with PROSPERO (CRD420251020815). Comprehensive searches were conducted on PubMed and Web of Science to identify studies based on the inclusion criteria (1) studies on resident Indian participants (cognitively healthy, mild cognitive impairment or dementia) (2) studies reporting plasma homocysteine levels, and (3) cross-sectional or longitudinal studies. Quality assessment was done using Joanna Briggs Institute critical appraisal tool. 16 studies of 283 records screened met the inclusion criteria. Meta-analysis of four studies comparing Alzheimer’s Disease (AD) patients and controls suggested a significantly higher homocysteine level in AD patients [SMD (95% CI) = 2.82 (0.29, 5.34); <i>p</i> = 0.03], though with high heterogeneity (I<sup>2</sup> = 99%).&#xa0;Systematic review of studies on MCI and cognitively unimpaired population showed inconsistent findings regarding the association of homocysteine with cognition. Elevated homocysteine seems to be associated with dementia in the Indian population, while the role of homocysteine in predementia and preclinical stages needs to be explored further.</p>

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Homocysteine as a Dual Vasculo-Metabolic Risk Factor for Cognitive Impairment Specific to the Indian Context: A Systematic Review and Meta-Analysis

  • 期刊论文

  • 发表日期：

    2026年2月2日

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  • G. Sandhya,
  • Mrinalini Rajashekhar,
  • Thomas Gregor Issac

摘要

India’s rapidly growing population is expected to face a substantial rise in cognitive impairment and dementia. Due to limited efficacy of existing treatment options, preventive strategies targeting modifiable risk factors are essential. One such factor is homocysteine, elevated levels of which have been studied as a modifiable vasculo-metabolic risk factor associated with cognitive impairment. This systematic review and meta-analysis aimed to synthesise current evidence on the relationship between homocysteine levels and cognition across cognitively unimpaired individuals, individuals with mild cognitive impairment and dementia in India. A systematic review and meta-analysis was registered with PROSPERO (CRD420251020815). Comprehensive searches were conducted on PubMed and Web of Science to identify studies based on the inclusion criteria (1) studies on resident Indian participants (cognitively healthy, mild cognitive impairment or dementia) (2) studies reporting plasma homocysteine levels, and (3) cross-sectional or longitudinal studies. Quality assessment was done using Joanna Briggs Institute critical appraisal tool. 16 studies of 283 records screened met the inclusion criteria. Meta-analysis of four studies comparing Alzheimer’s Disease (AD) patients and controls suggested a significantly higher homocysteine level in AD patients [SMD (95% CI) = 2.82 (0.29, 5.34); p = 0.03], though with high heterogeneity (I2 = 99%). Systematic review of studies on MCI and cognitively unimpaired population showed inconsistent findings regarding the association of homocysteine with cognition. Elevated homocysteine seems to be associated with dementia in the Indian population, while the role of homocysteine in predementia and preclinical stages needs to be explored further.