SALAs Offer No Edge Over Other NSAIDs in Reducing Alzheimer's Risk

Caroline Cassels

May 28, 2008

May 28, 2008 — Contrary to recent reports, selective Aβ-42–lowering agents (SALAs) — a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) that includes ibuprofen — offer no greater protection against Alzheimer's disease (AD) than other NSAIDs.

A pooled analysis that included data from 6 studies on NSAID use in 13,499 individuals showed those who used these medications had an overall 23% lower risk of developing AD than individuals who never used NSAIDs. However, the reduction in risk was not associated with the type of NSAID used.

"This is an interesting finding, because it seems to challenge a current theory that the NSAID group that includes ibuprofen may work better in reducing a person's risk of Alzheimer's," study investigator Peter P. Zandi, PhD, from Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, said in a statement from the American Academy of Neurology.

According to the study's lead author Chris Szekely, PhD, from Cedars Sinai Medical Center, in Los Angeles, California, the discrepancy between studies such as this and the negative clinical trials of NSAIDs in the treatment or prevention of AD need further exploration.

The study is published May 28 in Neurology.

SALAs vs Non-SALAs

For the study, the researchers pooled individual-level data from 6 prospective cohort studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.

Inclusion criteria for the 6 studies included diagnoses of incident AD made using clinical research criteria; systematic data on individual over-the-counter and prescription NSAIDs; and exposure measurements collected prior to dementia diagnosis.

NSAIDs were categorized as SALAs if they had been shown either in in vivo or in vitro models to lower Aβ-42 or as non-SALAs if they did not show selective Aβ-42 lowering.

According to the study, SALAs included diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, piroxicam, and sulindac. Non-SALAs included celecoxib, etodolac, ketoprofen, ketorolac, mefenamic acid, nabumetone, naproxen, and phenylbutazone.

The investigators also examined acetaminophen as a "control" medication because it is used for indications similar to those for NSAIDs but has a different mechanism of action. Dose information was not consistently available for medications and therefore was not examined.

More to Learn

The frequency of NSAID use at any time in the follow-up interval was 29.6%; aspirin was used by 47.0% and acetaminophen by 25.3%. Ibuprofen was the most commonly used SALA, accounting for 52.9% of NSAID use. Naproxen was the most commonly used non-SALA, accounting for 24.0% of NSAID use. Less than 1% of study participants reported use of selective COX-2 inhibitors.

Any NSAID use was associated with a 23% reduced risk of AD. However, there was no suggestion of greater AD risk reduction for SALAs vs non-SALAs. The investigators found aspirin users had a lower risk of AD, even among those who used aspirin alone and no other NSAID. Acetaminophen use was not linked to a lower AD risk.

"There is much to learn about the role of NSAIDs in the pathogenesis of AD, 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," they write.

The study was supported by the National Institutes of Health and the Canadian Institutes of Health Research. One of the authors, Dr. Kathleen A. Welsh-Bohmer, from Duke University, in Durham, North Carolina, reports having a royalty interest in several patents on the use of NSAIDs as a prevention/treatment for AD. No other conflicts of interest are reported.

Neurology. 2008;70:2291-2298.

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