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Homocysteine and Dementia: An International Consensus Statement
Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, Miller JW, Rosenberg IH et al.. Journal of Alzheimer's disease : JAD, 2018-01-01
Topic: Risk, prevention and care in population studies
Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 μmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia.
Key findings
- We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons.
Why it matters
An expert consensus group concluded that elevated plasma total homocysteine is a modifiable risk factor for cognitive decline, dementia, and Alzheimer's disease in older people. Intervention trials in elderly people with cognitive impairment showed that lowering homocysteine with B vitamins slows brain atrophy and cognitive decline, though the statement is based on review of existing evidence rather than a new trial.
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Study details
- Evidence strengthLow
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2 / 5 | 2018 — within 10 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 | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 362 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 36.2 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 5 / 6 | Cited 26.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 116 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rima Obeid: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29480200) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
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Read the original
- DOI: 10.3233/jad-171042
- PubMed: 29480200
- Original source →
- Free full text: Journal of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Smith, A. D., Refsum, H., Bottiglieri, T., Fenech, M., Hooshmand, B., McCaddon, A., et al. (2018). Homocysteine and Dementia: An International Consensus Statement. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-171042
Vancouver
Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, et al. Homocysteine and Dementia: An International Consensus Statement. Journal of Alzheimer's disease : JAD. 2018. doi:10.3233/jad-171042. PMID: 29480200.
BibTeX
@article{smith2018-29480200,
author = {Smith, A. D. and Refsum, H. and Bottiglieri, T. and Fenech, M. and Hooshmand, B. and McCaddon, A. and Miller, J. W. and Rosenberg, I. H. and others},
title = {{Homocysteine and Dementia: An International Consensus Statement}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2018},
doi = {10.3233/jad-171042},
pmid = {29480200},
url = {https://doi.org/10.3233/jad-171042}
}
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