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Title: NSAIDs May Be Equally Effective at Reducing Risk of Alzheimer's Disease

"NSAIDs May Be Equally Effective at Reducing Risk of Alzheimer's Disease"

NEW YORK -- May 28, 2008 -- Different types of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and aspirin, appear to be equally effective in lowering the risk of Alzheimer's disease, according to a study published in the May 28 online issue of [Neurology, the medical journal of the American Academy of Neurology. Experts have debated whether a certain group of NSAIDs which includes ibuprofen may be more beneficial than another group which includes naproxen and aspirin.

Using information from 6 different studies, researchers examined data on NSAID use in 13,499 people without dementia. Over the course of these 6 studies, 820 participants developed Alzheimer's disease. Researchers found that people who used NSAIDs had 23% lower risk of developing Alzheimer's disease compared with those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken.

One hypothesis held that the subset of NSAIDs known as selective amyloid (A)-beta-42-lowering agents (SALAs) were responsible for this apparent reduction in Alzheimer's risk. SALAs included diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, piroxicam, and sulindac. Non-SALAs included aspirin, celecoxib, etodolac, ketoprofen, ketorolac, mefanamic acid, nabumetone, naproxen, and phenylbutazone.

Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, the researchers examined their use alone and in combination. Resulting adjusted hazard ratios (aHRs) were 0.82 (95% confidence interval [CI], 0.67-0.99) for SALAs only, 0.60 (95% CI, 0.40-0.90) for non-SALAs only, and 0.87 (95% CI, 0.57-1.33) for both NSAIDs (Wald test for differences, P = .32). The 40.7% of participants who used aspirin also showed reduced risk of Alzheimer's, even when they used no other NSAIDs (aHR = 0.78; 95% CI, 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR= 0.93; 95% CI, 0.76-1.13).

The study concluded there was no apparent advantage in Alzheimer's risk reduction for the subset of NSAIDs shown to selectively lower A-beta-42, suggesting that all conventional NSAIDs, including aspirin, have a similar protective effect in humans.

"This is an interesting finding because it seems to challenge a current theory that the NSAID group which includes ibuprofen may work better in reducing a person's risk of Alzheimer's," said study author Peter P. Zandi, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. "The NSAID group that includes ibuprofen was thought to target a certain type of plaque in the brain found in Alzheimer's patients. But our results suggest there may be other reasons why these drugs may reduce the risk of Alzheimer's."

The study's lead author, Chris Szekely, PhD, Cedars Sinai Medical Center, Los Angeles, California, said the discrepancy between studies such as this one and the negative clinical trials of NSAIDs in treatment or prevention of Alzheimer's needs to be further explored. There is much to learn about the role of NSAIDs in the pathogenesis of Alzheimer's, including whether the putative neuroprotective effects of NSAIDs depend upon the timing, amount, or duration of their use or on particular characteristics of the subgroups of people who take them.

Source: American Academy of Neurology

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