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Homocysteine and folate as risk factors for dementia and Alzheimer disease
Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, Licastro F.. The American journal of clinical nutrition, 2005-09-01
Topic: Amyloid, tau and blood-test diagnosis
Background In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results. Objective We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population. Design A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12. Results Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 micromol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations ( Conclusions Elevated plasma tHcy concentrations and low serum folate concentrations are independent predictors of the development of dementia and AD.
Key findings
- Background In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia.
- Incidence studies of this issue are few and have produced conflicting results.
- Results Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD.
Why it matters
In 816 older adults followed for an average of 4 years, elevated plasma homocysteine and low serum folate were independent predictors of dementia and Alzheimer's disease. This identifies risk factors but does not show that lowering homocysteine or raising folate prevents dementia.
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Study details
- Study designcross-sectional
- Participants816
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of clinical nutrition) |
| Journal's citation record | 3 / 4 | American Journal of Clinical Nutrition: journal h-index 499 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 2 / 4 | 816 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 | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 449 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.5 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 5 / 6 | Cited 20.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 24 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 | 2 / 4 | Last-listed author Federico Licastro: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bologna: institution h-index 989 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16155278) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 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. The record names 8 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
Ravaglia, G., Forti, P., Maioli, F., Martelli, M., Servadei, L., Brunetti, N., et al. (2005). Homocysteine and folate as risk factors for dementia and Alzheimer disease. The American journal of clinical nutrition. https://doi.org/10.1093/ajcn.82.3.636
Vancouver
Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. The American journal of clinical nutrition. 2005. doi:10.1093/ajcn.82.3.636. PMID: 16155278.
BibTeX
@article{ravaglia2005-16155278,
author = {Ravaglia, G. and Forti, P. and Maioli, F. and Martelli, M. and Servadei, L. and Brunetti, N. and Porcellini, E. and Licastro, F.},
title = {{Homocysteine and folate as risk factors for dementia and Alzheimer disease}},
journal = {The American journal of clinical nutrition},
year = {2005},
doi = {10.1093/ajcn.82.3.636},
pmid = {16155278},
url = {https://doi.org/10.1093/ajcn.82.3.636}
}
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