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Elevated Blood Homocysteine and Risk of Alzheimer’s Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies

Abstract

Objective

To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer’s disease (AD) by performing a meta-analysis based on updated published data.

Methods

We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk.

Results

From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7–10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23–1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger’s test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01–1.44, Q value=41.92.

Conclusions

The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.

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Data availability statement: Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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Funding

Funding information: The research reported did not receive any specific grant from funding agencies in the public, commercial, or not- for- profit sectors.

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Correspondence to Carlo Cervellati.

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Conflicts of interest: All authors declare that they have no conflicts of interest.

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Zuin, M., Cervellati, C., Brombo, G. et al. Elevated Blood Homocysteine and Risk of Alzheimer’s Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies. J Prev Alzheimers Dis 8, 329–334 (2021). https://doi.org/10.14283/jpad.2021.7

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Key words

  • Alzheimer’s disease
  • homocysteine
  • meta-analysis
  • prospective studies