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Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD.. International journal of geriatric psychiatry, 2011-07-21
Topic: Risk, prevention and care in population studies
Background Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study. Methods This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models. Results The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P Conclusion In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.
Key findings
- In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI).
- Results The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo.
- There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037).
Why it matters
In this two-year trial in people aged 70 or over with mild cognitive impairment, daily folic acid, vitamin B12 and vitamin B6 left blood homocysteine 30% lower than placebo and stabilised executive function. There was also a significant benefit on global cognition among participants whose homocysteine started above the median. The authors call it a small trial in which B vitamins appear to slow decline, and say further trials are needed to see whether the treatment slows or prevents conversion from MCI to dementia.
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Study details
- Participants133
- Evidence strengthLow
How this study scored 69/100
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 (International journal of geriatric psychiatry) |
| Journal's citation record | 2 / 4 | International Journal of Geriatric Psychiatry: journal h-index 190 (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 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 133 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 | 6 / 7 | Cited 457 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.6 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 21.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 56 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author A. David Smith: h-index 125 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21780182) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 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. Check the citation against the original before you use it.
APA 7th
de Jager, C. A., Oulhaj, A., Jacoby, R., Refsum, H., & Smith, A. D. (2012). Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. International journal of geriatric psychiatry. https://doi.org/10.1002/gps.2758
Vancouver
de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. International journal of geriatric psychiatry. 2012. doi:10.1002/gps.2758. PMID: 21780182.
BibTeX
@article{dejager2012-21780182,
author = {de Jager, C. A. and Oulhaj, A. and Jacoby, R. and Refsum, H. and Smith, A. D.},
title = {{Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial}},
journal = {International journal of geriatric psychiatry},
year = {2012},
doi = {10.1002/gps.2758},
pmid = {21780182},
url = {https://doi.org/10.1002/gps.2758}
}
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