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Am Fam Physician. 2004;69(3):701

Cholinesterase inhibitors are commonly used to alleviate the symptoms of cognitive dysfunction in patients with Alzheimer's disease. Currently, researchers are evaluating the role of anti-inflammatory medications in preventing or modifying the course of Alzheimer's disease, with trials to date showing mixed results. Aisen and colleagues hypothesized that nonsteroidal anti-inflammatory drugs (NSAIDs) can slow the rate of cognitive decline in mild to moderate Alzheimer's disease over one year.

Using a three-way design, patients were randomized in double-blind fashion to treatment with rofecoxib, naproxen, or placebo. To be included, patients had to be older than 50 years and have a Mini-Mental State Examination score of 13 to 26. The primary outcome measure was a one-year change in score on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale, looking for a 50 percent reduction in cognitive decline over the study period compared with the placebo group. Secondary outcomes included additional assessment scales.

The 351 participants were assigned to three groups, with the ADAS-Cog score obtained in 76 percent of the naproxen group, 73 percent of the rofecoxib group, and 79 percent of the placebo group. In addition, eight patients in the rofecoxib group, 10 in the naproxen group, and six in the placebo group were taking cholinesterase inhibitors. Neither treatment had a beneficial impact on the ADAS-Cog score. The results of other analyses were similar, with no significant difference in the rate of decline among the three groups. Of the other assessments, the Alzheimer's Disease Cooperative Study activities of daily living (ADCS-ADL) score showed a trend toward a beneficial effect in the rofecoxib group. NSAIDs were associated with more minor adverse effects than placebo, but gastrointestinal tract symptoms did not differ among the groups. In this study, NSAIDs did not slow cognitive decline in patients with mild to moderate Alzheimer's disease. The slightly better ADCS-ADL score with rofecoxib is imputed to an analgesic effect.

The authors state that higher dosages or longer administration of NSAIDs could show some benefit. In addition, this trial did not address primary prevention of Alzheimer's disease with NSAID administration.

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