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Homocysteine, B Vitamins, and Cognitive Impairment
Smith AD, Refsum H.. Annual review of nutrition, 2016-07-01
Topic: Risk, prevention and care in population studies
Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process. Homocysteine may interact with both risk factors and protective factors, thereby identifying people at risk but also providing potential strategies for early intervention. Public health steps to slow cognitive decline should be promoted in individuals who are at risk of dementia, and more trials are needed to see if simple interventions with nutrients can prevent progression to dementia.
Key findings
- Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia.
- In contrast, trials in high-risk subjects, which have taken into account the baseline B vitamin status, show a slowing of cognitive decline and of atrophy in critical brain regions, results that are consistent with modification of the Alzheimer's disease process.
Why it matters
This review reports that elevated homocysteine is linked to cognitive decline and dementia, and that some B vitamin trials in high-risk people showed slower decline and less brain shrinkage. It calls for more trials to see whether nutrient treatment can prevent progression to dementia.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (Annual review of nutrition) |
| Journal's citation record | 2 / 4 | Annual Review of Nutrition: journal h-index 244 (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 | 1 / 5 | 2016 — 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 | 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 515 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 42.9 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 8.7× 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 | 3 / 4 | Cited 149 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Helga Refsum: h-index 95 (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 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27431367) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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Read the original
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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
Smith, A. D., & Refsum, H. (2016). Homocysteine, B Vitamins, and Cognitive Impairment. Annual review of nutrition. https://doi.org/10.1146/annurev-nutr-071715-050947
Vancouver
Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annual review of nutrition. 2016. doi:10.1146/annurev-nutr-071715-050947. PMID: 27431367.
BibTeX
@article{smith2016-27431367,
author = {Smith, A. D. and Refsum, H.},
title = {{Homocysteine, B Vitamins, and Cognitive Impairment}},
journal = {Annual review of nutrition},
year = {2016},
doi = {10.1146/annurev-nutr-071715-050947},
pmid = {27431367},
url = {https://doi.org/10.1146/annurev-nutr-071715-050947}
}
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