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No Benefit of (Some) NSAIDs in Alzheimer's Disease Progression

Neither rofecoxib nor naproxen prevented cognitive decline in patients with AD.

Epidemiologic associations and results of clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) might help prevent or slow the development of Alzheimer's disease (AD; Journal Watch Nov 23 2001). In this multicenter U.S. trial, 351 AD patients (age, >50; Mini-Mental State Exam score, 13-26) were randomized to receive rofecoxib (25 mg daily), naproxen sodium (220 mg twice daily), or placebo. Regular use of medications such as cholinesterase inhibitors, estrogen, aspirin, and vitamin E was allowed.

At 1 year, intent-to-treat analyses using several standardized cognitive measures showed no significant difference in cognitive decline among the 3 groups. Fatigue, dizziness, and hypertension were more common in the treatment groups, as were serious adverse events (e.g., gastrointestinal tract bleeding, stroke, subdural hematoma, myocardial infarction) overall.

Comment: Despite the biologic plausibility of an NSAID-mediated decrease in inflammation and ß-amyloid production in Alzheimer's disease, this study did not show any such benefit with either nonselective or cyclooxygenase (COX)-2 blockage. An editorialist notes that researchers should explore the value of NSAIDs in patients with other types of cognitive dysfunction, differentiate primary prevention from slowing progression in high-risk patients, delineate the potential benefits of COX-1 vs. COX-2 inhibition, and explore the risks and benefits of longer NSAID treatment.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine June 27, 2003

Citation(s):

Aisen PS et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: A randomized controlled trial. JAMA 2003 Jun 4; 289:2819-26.

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• Medline abstract (Free)

Launer LJ. Nonsteroidal anti-inflammatory drugs and Alzheimer disease: What's next? JAMA 2003 Jun 4; 289:2865-7.

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• Medline abstract (Free)