Can NSAIDs Prevent Alzheimer Disease?

Although inflammation plays a role in the pathogenesis of Alzheimer disease (AD), nonsteroidal anti-inflammatory drugs (NSAIDs) have not slowed the progression of early AD in several clinical trials (Journal Watch Feb 6 2004 and Journal Watch Jun 27 2003). But can NSAIDs prevent or delay the development of AD?

The ADAPT trial included people aged 70 or older who had no evidence of dementia or cognitive impairment, but had at least one first-degree relative with Alzheimer-like dementia. Participants were randomized to receive celecoxib (200 mg twice daily), naproxen (220 mg twice daily), or placebo. The trial was terminated in December 2004 when another study reported increased cardiovascular risk with celecoxib. At that point, 2528 people had been enrolled in ADAPT, and median follow-up was about 2 years (the original intent was 7 years of follow-up).

According to standardized cognitive testing and further evaluation of subjects with abnormal test results, neither celecoxib nor naproxen prevented AD or mild cognitive impairment. In fact, the annual risk for AD was higher in the celecoxib and naproxen groups (about 1%) than in the placebo group (about 0.5%), a difference that approached statistical significance.