Is High Homocysteine Level a Risk Factor for Cognitive Decline in Elderly? A Systematic Review, Meta-Analysis, and Meta-Regression
Abstract
Objective [corrected] High homocysteine (Hct) has been causatively linked to Alzheimer disease (AD) and vascular dementia (VaD) in old age, but research methodologies and outcome measures are heterogeneous. It remains unclear whether the findings can be generalized across studies. Methods Random-effects meta-analyses were conducted on studies examining the relationship between Hct level and risk of developing dementia/cognitive decline between comparison groups. Meta-regression identified patient- and trial-related factors, which may contribute to heterogeneity. Results Seventeen relevant studies (6,122 participants; 13 cross-sectional and fourprospective studies) were included. Compared with controls, Hct was significantly elevated in AD (pooled standardized mean difference [SMD]: 0.59; 95% confidence interval [CI]: 0.38-0.80; significant heterogeneity: τ = 0.105) and VaD (pooled SMD: 1.30; 95% CI: 0.75-1.84; significant heterogeneity: τ = 0.378). Meta-regression identified mean age as significant moderator for AD versus controls and mean age and mean folate levels as significant moderators for VaD versus controls. Hct was significantly higher in VaD relative to AD (pooled SMD: 0.48; 95% CI: 0.23-0.73; moderately significant heterogeneity: τ = 0.076); proportion of men and mean folate levels were significant moderators. High-Hct level was not associated with risk of developing dementia in prospective studies (pooled odds ratio: 1.34; 95% CI: 0.94-1.91, nonsignificant heterogeneity: τ = 0.048). Conclusion Individuals with AD and VaD have higher Hct levels than controls; however, a causal relationship between high-Hct level and risk of developing dementia is not supported. More prospective studies and randomized controlled trials are required to test the therapeutic benefits of lowering Hct levels.
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The results of meta-regressions suggest observational associations but not causations due to ecological fallacy.
“Furthermore, the results of meta-regressions suggest observational associations but not causations due to ecological fallacy [100].”
From Prevalence of Burnout in Medical and Surgical Residents: A Meta-Analysis (2019) · cites this paper as [100]
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- Authors
- Ho, R. C. M., Cheung, M. W. L., Fu, E., Win, H. H., Zaw, M. H., Ng, A., & Mak, A.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Ho, Roger C.M.
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 19
- Issue
- 7
- Pages
- 607-617
- ISSN
- 1064-7481 (ISSN-L)
- OpenAlex
- W2051627448
- Cited by
- 99
- References
- 40
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 9 · 2016: 7 · 2015: 10 · 2014: 4 · 2013: 10 · 2012: 13
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- homocysteine, cognitive decline, Alzheimer's disease, vascular dementia, dementia risk factors, older adults, folic acid, age as moderator, sex differences, causal relationship
- MeSH terms
- Aged, Alzheimer Disease, Dementia, Female, Folic Acid, Homocysteine, Humans, Male, Middle Aged, Regression Analysis, Risk Factors, Vitamin B 12, Dementia, Vascular, Odds Ratio, Dietary Supplements
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