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A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people
Kwok T, Lee J, Law CB, Pan PC, Yung CY, Choi KC, Lam LC.. Clinical nutrition (Edinburgh, Scotland), 2011-01-08
Topic: Risk, prevention and care in population studies
Introduction Whether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear. Methods and materials 140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18. Results Trial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 μmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 μmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003). Conclusion Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.
Key findings
- Results Trial groups were well matched in baseline characteristics.
- There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003).
- Conclusion Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.
Why it matters
In a 24-month placebo-controlled trial of 140 people with mild to moderate Alzheimer's disease or vascular dementia, daily methylcobalamin (1 mg) plus folic acid (5 mg) lowered blood homocysteine from about 14.1 to 9.3 μmol/L but produced "no significant group difference in changes in any of the neuropsychological scores." The only signal was a subgroup finding: among people with homocysteine above 13 μmol/L, decline in one MDRS domain (construction) was smaller on supplements (median 0 vs 2 points). The authors conclude that homocysteine lowering "did not significantly reduce global cognitive decline" in people who already have dementia.
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Study details
- Participants140
- Evidence strengthLow
How this study scored 59/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical nutrition (Edinburgh, Scotland)) |
| Journal's citation record | 2 / 4 | Clinical Nutrition: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 2 / 4 | 140 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 | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 83 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.9 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 5.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author LINDA C. W. LAM: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Chinese University of Hong Kong: institution h-index 1,100 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21216507) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Kwok, T., Lee, J., Law, C. B., Pan, P. C., Yung, C. Y., Choi, K. C., et al. (2011). A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clinical nutrition (Edinburgh, Scotland). https://doi.org/10.1016/j.clnu.2010.12.004
Vancouver
Kwok T, Lee J, Law CB, Pan PC, Yung CY, Choi KC, et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clinical nutrition (Edinburgh, Scotland). 2011. doi:10.1016/j.clnu.2010.12.004. PMID: 21216507.
BibTeX
@article{kwok2011-21216507,
author = {Kwok, T. and Lee, J. and Law, C. B. and Pan, P. C. and Yung, C. Y. and Choi, K. C. and Lam, L. C.},
title = {{A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people}},
journal = {Clinical nutrition (Edinburgh, Scotland)},
year = {2011},
doi = {10.1016/j.clnu.2010.12.004},
pmid = {21216507},
url = {https://doi.org/10.1016/j.clnu.2010.12.004}
}
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