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Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial
Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S et al.. JAMA, 2003-06-01
Topic: Amyloid, tau and blood-test diagnosis
Context Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. Objective To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. Design Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. Setting Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. Participants Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. Interventions Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. Main outcome measures The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). Results The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. Conclusion The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
Key findings
- Context Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease.
- Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death).
- Results The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]).
- Results of secondary analyses showed no consistent benefit of either treatment.
- Conclusion The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
Why it matters
In this one-year, double-blind trial at 40 Alzheimer's Disease Cooperative Study centers, 351 people with mild-to-moderate Alzheimer disease took rofecoxib, low-dose naproxen or a placebo. Average decline on the ADAS-Cog memory-and-thinking test was 7.6 points with rofecoxib, 5.8 with naproxen and 5.7 with placebo, which the authors report as not significantly different, and secondary measures "showed no consistent benefit of either treatment." The authors conclude these drugs do "not slow cognitive decline" in this group, and fatigue, dizziness, high blood pressure and serious side effects were more common on the active drugs.
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Study details
- Participants474
- Evidence strengthHigh
How this study scored 61/100
Published in a top-tier journal, and it is a randomised controlled 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 59 of the 96 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 2003 — older than 20 years, still counted |
| Sample size | 2 / 4 | 474 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 | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.2 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 1 / 6 | Cited 0.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 63 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 | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 0 / 3 | Georgetown University Medical Center: institution h-index 564 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12783912) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 59 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 96 points we could judge it on is 61 out of 100. |
| Total | 61 / 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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., et al. (2003). Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. https://doi.org/10.1001/jama.289.21.2819
Vancouver
Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003. doi:10.1001/jama.289.21.2819. PMID: 12783912.
BibTeX
@article{aisen2003-12783912,
author = {Aisen, P. S. and Schafer, K. A. and Grundman, M. and Pfeiffer, E. and Sano, M. and Davis, K. L. and Farlow, M. R. and Jin, S. and others},
title = {{Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial}},
journal = {JAMA},
year = {2003},
doi = {10.1001/jama.289.21.2819},
pmid = {12783912},
url = {https://doi.org/10.1001/jama.289.21.2819}
}
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