Home › Research › Treatments
Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group
Rogers SL, Doody RS, Mohs RC, Friedhoff LT.. Archives of internal medicine, 1998-05-01
Topic: Amyloid, tau and blood-test diagnosis
Background Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer disease. This phase 3 study was 1 of 2 pivotal trials undertaken to establish the efficacy and safety of using donepezil in patients with mild to moderately severe Alzheimer disease. Objectives To further examine the efficacy and safety of using donepezil in the treatment of patients with mild to moderately severe Alzheimer disease. To examine the relationships between plasma donepezil concentrations, inhibition of red blood cell acetylcholinesterase activity, and clinical response. Methods This was a 12-week, double-blind, placebo-controlled, parallel-group trial with a 3-week single-blind washout. Outpatients at 23 centers in the United States were randomized to receive placebo, 5 mg of donepezil hydrochloride, or 10 mg of donepezil hydrochloride (5 mg/d during week 1 then 10 mg/d thereafter) administered once daily at bedtime. Primary efficacy was measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change including caregiver information (CIBIC plus). Results A total of 468 patients entered the study, more than 97% of whom were included in the intention-to-treat (end point) analyses. The use of donepezil produced statistically significant improvements in ADAS-cog, CIBIC plus, and Mini-Mental State Examination scores, relative to placebo. The mean drug-placebo differences, at end point, for the groups receiving 5 mg/d and 10 mg/d of donepezil hydrochloride were, respectively, 2.5 and 3.1 units for ADAS-cog (P Conclusion Donepezil hydrochloride (5 and 10 mg) administered once daily is a well-tolerated and efficacious agent for treating the symptoms of mild to moderately severe Alzheimer disease.
Key findings
- Results A total of 468 patients entered the study, more than 97% of whom were included in the intention-to-treat (end point) analyses.
- The use of donepezil produced statistically significant improvements in ADAS-cog, CIBIC plus, and Mini-Mental State Examination scores, relative to placebo.
Why it matters
In this 15-week trial of 468 patients with mild to moderately severe Alzheimer disease, donepezil produced statistically significant improvements in cognition and global function compared with placebo. This supports donepezil as an effective treatment for these symptoms in this population.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designclinical trial
- Participants468
- Evidence strengthHigh
How this study scored 72/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 69 of the 96 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of internal medicine) |
| Journal's citation record | 3 / 4 | Archives of Internal Medicine: journal h-index 462 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 2 / 4 | 468 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 | 6 / 7 | Cited 777 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.9 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 5 / 6 | Cited 37.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 33 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Sharon L. Rogers holds only 8 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Eisai (United States): institution h-index 251 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9588436) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 69 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 69 of the 96 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Rogers, S. L., Doody, R. S., Mohs, R. C., & Friedhoff, L. T. (1998). Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Archives of internal medicine. https://doi.org/10.1001/archinte.158.9.1021
Vancouver
Rogers SL, Doody RS, Mohs RC, Friedhoff LT. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Archives of internal medicine. 1998. doi:10.1001/archinte.158.9.1021. PMID: 9588436.
BibTeX
@article{rogers1998-9588436,
author = {Rogers, S. L. and Doody, R. S. and Mohs, R. C. and Friedhoff, L. T.},
title = {{Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group}},
journal = {Archives of internal medicine},
year = {1998},
doi = {10.1001/archinte.158.9.1021},
pmid = {9588436},
url = {https://doi.org/10.1001/archinte.158.9.1021}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
33 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Treatments
Also tagged “double-blind”
783 studies in the library carry the topic tag “double-blind”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 783 tagged studies.