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Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial
Seltzer B, Zolnouni P, Nunez M, Goldman R, Kumar D, Ieni J, Richardson S, Donepezil "402" Study Group.. Archives of neurology, 2004-12-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Objective To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease. Design Multicenter, randomized, double-blind, 24-week, placebo-controlled study that enrolled patients with early-stage Alzheimer disease. Patients were randomized in an approximately 2:1 ratio to donepezil, 5 mg/d, for the first 6 weeks, with a forced escalation to 10 mg/d thereafter (n = 96), or placebo (n = 57). The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale. Secondary efficacy measures included the Mini-Mental State Examination, the Computerized Memory Battery Test, the Clinical Dementia Rating Scale-Sum of the Boxes, the Patient Global Assessment Scale, and the Apathy Scale. Results Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point (last observation carried forward); treatment differences were 1.9 (P = .03), 2.3 (P = .008), and 2.3 (P = .001) points, respectively. Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6, 12, and 24 and at the end point (last observation carried forward); treatment differences were 1.4 (P = .02), 1.2 (P = .04), 1.4 (P = .03), and 1.8 (P = .002) points, respectively. Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales: facial recognition (P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population), first and last name total acquisition (P = .02), and name-face association delayed recall (P = .04). Donepezil was safe and well tolerated in this population; serious adverse events occurred in similar numbers of donepezil- and placebo-treated patients. Conclusion These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease, supporting the initiation of therapy early in the disease course to improve daily cognitive functioning.
What this study adds
Evidence grade: High
This is a trial of 96 participants. In this 24-week trial, donepezil improved scores on cognitive tests compared with placebo in people with early-stage Alzheimer disease. This shows donepezil can help with symptoms but the study did not test whether it changes the underlying disease.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Seltzer, B., Zolnouni, P., Nunez, M., Goldman, R., Kumar, D., Ieni, J., et al. (2004). Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial. Archives of neurology. https://doi.org/10.1001/archneur.61.12.1852
Vancouver
Seltzer B, Zolnouni P, Nunez M, Goldman R, Kumar D, Ieni J, et al. Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial. Archives of neurology. 2004. doi:10.1001/archneur.61.12.1852. PMID: 15596605.
BibTeX
@article{seltzer2004-15596605,
author = {Seltzer, B. and Zolnouni, P. and Nunez, M. and Goldman, R. and Kumar, D. and Ieni, J. and Richardson, S. and {Donepezil "402" Study Group}},
title = {{Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial}},
journal = {Archives of neurology},
year = {2004},
doi = {10.1001/archneur.61.12.1852},
pmid = {15596605},
url = {https://doi.org/10.1001/archneur.61.12.1852}
}
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.
Key findings
- Results Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point (last observation carried forward); treatment differences were 1.9 (P = .03), 2.3 (P = .008), and 2.3 (P = .001) points, respectively.
- Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales: facial recognition (P = .007 in the intent-to-treat population and P = .04 in the fully evaluable population), first and last name total acquisition (P = .02), and name-face association delayed recall (P = .04).
- Conclusion These data suggest significant treatment benefits of donepezil in early-stage Alzheimer disease, supporting the initiation of therapy early in the disease course to improve daily cognitive functioning.
Why it matters
In this 24-week trial, donepezil improved scores on cognitive tests compared with placebo in people with early-stage Alzheimer disease. This shows donepezil can help with symptoms but the study did not test whether it changes the underlying disease.
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Study details
- Participants96
- Evidence strengthHigh
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 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 | 2004 — older than 20 years, still counted |
| Sample size | 1 / 4 | 96 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) |
| Randomized / blinded | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 257 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.7 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Ben Seltzer: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Tulane University: institution h-index 735 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15596605) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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