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NSAIDs and Alzheimer’s: Jury Still Out

Study Shows All NSAIDs Equal for Prevention
By
WebMD Health News
Reviewed by Louise Chang, MD

May 28, 2008 -- It's still unclear whether nonsteroidal anti-inflammatory drugs (NSAIDs) lower Alzheimer's risk. But new research suggests that if they do, different types of NSAIDs work equally well.

Nearly a decade of investigation into the impact of NSAIDs on Alzheimer's seems to have only added to the confusion.

The only clinical trial to examine the subject, known as ADAPT, showed no evidence of a protective benefit for the NSAIDs naproxen and Celebrex. But that trial was stopped early because of concerns about potential cardiovascular risks with long-term use of the drugs.

Other types of studies have generally shown sporadic or regular NSAID use to lower the risk of Alzheimer's disease and cognitive decline in older people.

To further confuse matters, some animal studies suggest that the NSAID ibuprofen may be uniquely protective because the drug targets a specific plaque in the brain found in Alzheimer's patients.

"These studies raised a lot of controversy about whether the ADAPT researchers were studying the wrong NSAIDs," says Peter P. Zandi, PhD, of the Johns Hopkins Bloomberg School of Public Health.

NSAIDs and Alzheimer's

In an effort to address this question, Zandi and colleagues examined pooled data from three previously published and three previously unpublished observational studies involving 13,499 mostly elderly people who showed no evidence of dementia at enrollment.

Over the course of the studies, 820 of the participants were diagnosed with Alzheimer's disease.

Overall, any NSAID use was found to be associated with a 23% lower risk of developing Alzheimer's compared to never using NSAIDs. The reduction was greatest among regular users who took the pain relievers for at least two years.

But ibuprofen was found to be no more protective than naproxen, aspirin, or any other NSAID, Zandi tells WebMD.

Only the non-NSAID acetaminophen pain relievers, such as Tylenol, showed no protective benefit.

"Our findings are not consistent with the theory that certain NSAIDs are more protective than others," Zandi says.

The findings were reported today in the online edition of the journal Neurology.

Many Questions Remain

So what should the public take from the NSAID research?

The experts agree that there are still far too many unanswered questions to recommend their use for the prevention of Alzheimer's disease.

ADAPT study co-investigator Barbara K. Martin, PhD, tells WebMD that it is far from clear if the benefits of long-term NSAID use outweigh the risks. Among the most serious of these risks are stomach ulcers and bleeding.

Martin is an epidemiologist with the Johns Hopkins Bloomberg School of Public Health, but she was not involved in the Zandi study.

"We have to be very careful when we recommend taking medicines for prevention," she says. "There has to be good evidence of a benefit before we expose people to something that could be potentially harmful for the sake of preventing something that may or may not happen."

And even if NSAIDs are protective, it is still not clear when in life they should be taken to derive the cognitive benefit, Zandi says.

"Several studies have suggested that for people who already show evidence of cognitive decline, NSAIDs may have no effect or may even aggravate the condition," he says.

Zandi agrees that it is far too soon to recommend the use of NSAIDs to protect against Alzheimer's disease.

"The data are really interesting," he says. "It is clear that something is going on. We just don't know what it is."

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