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Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease
Morris JC, Cyrus PA, Orazem J, Mas J, Bieber F, Ruzicka BB, Gulanski B.. Neurology, 1998-05-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To evaluate the efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease (AD) of mild to moderate severity. Methods A prospective, 36-week, multicenter, double-blind, randomized, parallel group study of metrifonate in probable AD patients, including a 2-week screening period, a 26-week double-blind treatment period, and a follow-up visit at 8 weeks post-treatment. A total of 24 ambulatory clinics in the United States in a variety of settings, including contract research organizations, public health facilities, and universities. Patients met diagnostic criteria for probable AD as defined by the work group of the National Institute for Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association. Patients had Mini-Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen Modification) of Results After 26 weeks of metrifonate therapy, a 2.86-point treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the intent-to-treat AD patients. The treatment difference in the mean CIBIC-plus score at this time was 0.28 points (p = 0.0071). At week 26, treatment differences also were observed in the mean NPI total score (p = 0.0161). Analysis of the remaining secondary efficacy variables showed treatment differences that favored metrifonate but did not reach statistical significance. Metrifonate adverse events were predominantly mild in intensity. No hepatotoxicity was observed. Conclusions Metrifonate was safe and well-tolerated. It enhanced not only the cognitive and global function, but also the behavioral function of patients diagnosed with mild to moderate AD. Therefore, metrifonate appears to be useful in the symptomatic treatment of AD.
Key findings
- Patients had Mini-Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen Modification) of Results After 26 weeks of metrifonate therapy, a 2.86-point treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the intent-to-treat AD patients.
Why it matters
In this 26-week double-blind trial, the acetylcholinesterase inhibitor metrifonate produced a 2.86-point treatment difference on the ADAS-Cog and differences on global and behavioral measures in patients with mild to moderate Alzheimer's disease. It addresses symptom benefit only and does not show that metrifonate cures or prevents the disease.
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Study details
- Participants24
- Evidence strengthHigh
How this study scored 71/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised 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 | 1998 — older than 20 years, still counted |
| Sample size | 1 / 4 | 24 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 | 5 / 7 | Cited 289 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.6 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 6 / 6 | Cited 41.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Barbara Gulanski: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9595967) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 71 / 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 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.
APA 7th
Morris, J. C., Cyrus, P. A., Orazem, J., Mas, J., Bieber, F., Ruzicka, B. B., et al. (1998). Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease. Neurology. https://doi.org/10.1212/wnl.50.5.1222
Vancouver
Morris JC, Cyrus PA, Orazem J, Mas J, Bieber F, Ruzicka BB, et al. Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease. Neurology. 1998. doi:10.1212/wnl.50.5.1222. PMID: 9595967.
BibTeX
@article{morris1998-9595967,
author = {Morris, J. C. and Cyrus, P. A. and Orazem, J. and Mas, J. and Bieber, F. and Ruzicka, B. B. and Gulanski, B.},
title = {{Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease}},
journal = {Neurology},
year = {1998},
doi = {10.1212/wnl.50.5.1222},
pmid = {9595967},
url = {https://doi.org/10.1212/wnl.50.5.1222}
}
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