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Cited by 96Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Effects of Rofecoxib or Naproxen vs Placebo on Alzheimer Disease Progression: A Randomized Controlled Trial

Aisen, Paul S., Schafer, Kimberly A., Grundman, Michael, Pfeiffer, Eric, Sano, Mary, Davis, Kenneth L., Farlow, Martin R., Jin, Shelia +3 more·2003·JAMA
DOI 10.1001/jama.289.21.2819
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Abstract

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.

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  • Follow-up clinical trials of low-dose prednisone, low-dose aspirin, NSAIDs, and selective COX-2 inhibitors failed to show any reduction in rate of cognitive decline in mild to moderate Alzheimer disease.

    “However, follow-up clinical trials testing the effect of low-dose prednisone (Aisen et al., 2000), low dose aspirin (AD2000 Collaborative Group et al., 2008), NSAIDS (Aisen et al., 2003; de Jong et al., 2008), and selective COX-2 inhibitors (Aisen et al., 2003; Thal et al., 2005) failed to show any reduction in rate of cognitive decline in mild to moderate AD.”

    From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Aisen et al., 2003

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Authors
Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., Farlow, M. R., Jin, S., Thomas, R. G., Thal, L. J., & Study, F. T. A. D. C.
Affiliations
Georgetown University Medical Center (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2003-06-04
Volume
289
Issue
21
Pages
2819
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.289.21.2819
OpenAlex
W166560457
Cited by
5
References
27
Citations by year
2017: 1 · 2016: 1
FWCI
0.19
Type
journal article
Language
en
Open access
closed
Locations
JAMA (publishedVersion)
Funders
  • National Institute on Aging (U01‐AG10483, U19AG010483)
  • National Center for Research Resources (5 M01-RR13297)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
Alzheimer's disease, rofecoxib, naproxen, nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, cognitive decline, disease progression, neuroinflammation, adverse events, quality of life, activities of daily living, institutionalization, placebo comparison, hypertension, dizziness, cholinesterase inhibitors, estrogen

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