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Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression
Ho RC, Cheung MW, Fu E, Win HH, Zaw MH, Ng A, Mak A.. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2011-07-01
Topic: Risk, prevention and care in population studies
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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APA 7th
Ho, R. C., Cheung, M. W., Fu, E., Win, H. H., Zaw, M. H., Ng, A., et al. (2011). Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. https://doi.org/10.1097/jgp.0b013e3181f17eed
Vancouver
Ho RC, Cheung MW, Fu E, Win HH, Zaw MH, Ng A, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2011. doi:10.1097/jgp.0b013e3181f17eed. PMID: 21705865.
BibTeX
@article{ho2011-21705865,
author = {Ho, R. C. and Cheung, M. W. and Fu, E. and Win, H. H. and Zaw, M. H. and Ng, A. and Mak, A.},
title = {{Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression}},
journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry},
year = {2011},
doi = {10.1097/jgp.0b013e3181f17eed},
pmid = {21705865},
url = {https://doi.org/10.1097/jgp.0b013e3181f17eed}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- 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).
Why it matters
This meta-analysis of 17 studies with 6,122 participants found that homocysteine was significantly elevated in Alzheimer disease and vascular dementia compared with controls, but high homocysteine level was not associated with risk of developing dementia or cognitive decline. The authors note significant heterogeneity across studies.
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Study details
- Study designmeta-analysis
- Participants6,122
- Evidence strengthHigh
How this study scored 59/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry) |
| Journal's citation record | 2 / 4 | American Journal of Geriatric Psychiatry: journal h-index 178 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 6,122 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 98 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.8 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Anselm Mak: h-index 46 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | National University of Singapore: institution h-index 1,166 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21705865) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
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