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Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial
Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, Xu Y, Murthy AK.. Neurology, 2009-01-28
Topic: Risk, prevention and care in population studies
Background Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. Methods In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. Results The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p Conclusions Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.
Key findings
- Results The dual primary efficacy endpoint was not reached.
- We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint.
- Patient Global Assessment scores favored donepezil at all time points except week 12 (p Conclusions Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function.
Why it matters
In this 48-week placebo-controlled trial in people with mild cognitive impairment, donepezil did not meet its main test of success: it gave "small but significant" gains on a cognitive test but no change on the primary measure of everyday/global function. The authors suggest standard measures may be "insensitive to change in MCI", and patients rated themselves as better on donepezil — a subjective signal, not proof of benefit. The trial does not show that donepezil slows or prevents progression to Alzheimer's.
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Study details
- Evidence strengthHigh
How this study scored 68/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for sample size and 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 | 2009 — 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 213 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.2 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 7.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 2 / 4 | Cited 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Anita K. Murthy: h-index 9 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | New York University: institution h-index 1,612 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19176895) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 68 / 100 | — |
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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. 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
Doody, R. S., Ferris, S. H., Salloway, S., Sun, Y., Goldman, R., Watkins, W. E., et al. (2009). Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. https://doi.org/10.1212/01.wnl.0000344650.95823.03
Vancouver
Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009. doi:10.1212/01.wnl.0000344650.95823.03. PMID: 19176895.
BibTeX
@article{doody2009-19176895,
author = {Doody, R. S. and Ferris, S. H. and Salloway, S. and Sun, Y. and Goldman, R. and Watkins, W. E. and Xu, Y. and Murthy, A. K.},
title = {{Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial}},
journal = {Neurology},
year = {2009},
doi = {10.1212/01.wnl.0000344650.95823.03},
pmid = {19176895},
url = {https://doi.org/10.1212/01.wnl.0000344650.95823.03}
}
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