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Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment
Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD.. Proceedings of the National Academy of Sciences of the United States of America, 2013-05-20
Topic: Amyloid, tau and blood-test diagnosis
Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., et al. (2013). Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1301816110
Vancouver
Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, et al. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences of the United States of America. 2013. doi:10.1073/pnas.1301816110. PMID: 23690582.
BibTeX
@article{douaud2013-23690582,
author = {Douaud, G. and Refsum, H. and de Jager, C. A. and Jacoby, R. and Nichols, T. E. and Smith, S. M. and Smith, A. D.},
title = {{Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2013},
doi = {10.1073/pnas.1301816110},
pmid = {23690582},
url = {https://doi.org/10.1073/pnas.1301816110}
}
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
- In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y.
- In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment.
- Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline.
Why it matters
In elderly people with mild cognitive impairment, high-dose B-vitamin treatment slowed shrinkage of brain regions vulnerable to Alzheimer's disease, and this benefit was confined to those with high homocysteine levels. This suggests that lowering homocysteine with B vitamins may slow brain atrophy and cognitive decline in this specific group, though it does not show the disease can be cured or prevented.
Study details
- Evidence strengthHigh
How this study scored 74/100
Published in a peer-reviewed journal, and it is a randomized controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| 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 (pubmed indexes it as a clinical or observational study) |
| Randomized / blinded | 1 / 2 | Randomized (as stated in the record) |
| Times cited | 6 / 7 | Cited 517 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 34.5 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 6 / 6 | Cited 40.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 84 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) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23690582) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 74 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1073/pnas.1301816110
- PubMed: 23690582
- Original source →
- Free full text: Proceedings of the National Academy of Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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