Alzheimer's and NSAIDs: Translating the News

Studies reach conflicting conclusions about whether painkillers like naproxen prevent dementia.

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I remember visiting a sick uncle when I was younger. Gradually, he became more and more confused—less aware of who his visitors were. He had dementia, as did my great-grandmother, who my mom says would get so disoriented that she'd even try to jump out the window of the family home.

Knowing my family history, I've been interested in studies that have come out in recent weeks, suggesting that taking nonsteroidal anti-inflammatory drugs, or NSAIDs, like naproxen, ibuprofen, and Celebrex, may reduce your risk of developing Alzheimer's disease later in life. But because the findings—including one just out today—conflict with those of other recent studies, I decided to sort out the details.

The latest study, published in Neurology, suggests that naproxen, ibuprofen, and aspirin may reduce the risk of Alzheimer's disease. The analysis looked at results from six previous studies. The authors found that those who took NSAIDs had a 23 percent reduced risk of Alzheimer's disease in comparison with those who didn't take the medicines. And another study, published earlier this month in Neurology, found that those who take ibuprofen on a regular basis for five years may be less likely to develop Alzheimer's disease.

But not all the news about NSAIDs' potential to reduce the risk of dementia has been positive. A study appearing in Neurology in April 2007 found that naproxen and Celebrex don't seem to prevent Alzheimer's disease. This finding was particularly disappointing because the study was especially rigorous—a large clinical trial scheduled to run for 10 years. (It was stopped after three years, however, when news broke in 2004 that Vioxx—a medication in the same class as Celebrex—might up the risk of cardiovascular disease in some people.)

Why do researchers think that NSAIDs—though not other analgesics, like Tylenol—might help reduce the risk of dementia? The theory is that the medications might reduce inflammation in the brain that experts think is tied to the development of Alzheimer's disease. Maybe if you get to the root of the inflammation early enough, they say, you can prevent the development of the disease later in life.

"For about 20 years there have been observational studies suggesting that anti-inflammatories might provide a protective effect," says Paul Aisen, a professor in the department of neurosciences at the University of California-San Diego. But all of the randomized controlled trials—including the 2007 study—"have failed to support this idea," he says.

Experts offer many reasons why studies have failed to agree with one another. Perhaps it's because each study has looked at different combinations of medications—naproxen and ibuprofen in one, for instance, and Celebrex and ibuprofen in another. Or, maybe it's because of the age of the participants. It's still not clear whether it makes a difference if people start taking NSAIDs when they're relatively young, rather than waiting until they're older and may already be sick. "We're beginning to get a picture here that by the time people already have mild or full-blown [dementia] symptoms, these drugs are not helpful and may in fact be harmful," says John C. S. Breitner, one of the authors of the new study and an Alzheimer's expert with the VA Puget Sound Health Care System and the University of Washington.

Despite the flurry of news in this area in the last several weeks, "we're at a point where we don't know the answer," says Peter Zandi, another author of the new study and an assistant professor at Johns Hopkins's Bloomberg School of Public Health. "The observational studies say there's something here, but the randomized trials don't bear that out. So maybe there's something wrong with observational studies in that they're biased in some way, or maybe there's something wrong with trials in how they're designed."

So far, the evidence for taking NSAIDs to prevent dementia doesn't outweigh the known health risks of the medications, experts note. "We now have fairly worrisome evidence—it's not proof—that all of the NSAIDs could be harmful in terms of increasing a person's chance of having a heart attack or a stroke," Breitner says. The medicines also carry other risks that can be substantial, particularly in older, frail people, such as gastrointestinal and kidney problems, Aisen says. And combining different types of NSAIDs—such as aspirin and ibuprofen—may pose its own concerns.

The bottom line is it's too soon to say if there's any benefit to taking a daily NSAID for dementia prevention. "You do not want to start taking an NSAID if you're taking it because you think you're going to be reducing the risk of Alzheimer's disease," Zandi says. "The scientific community needs to better understand what the relationship is between using these NSAIDs and the effect on cognitive function and risk of Alzheimer's disease before we can start making any sort of recommendations about their use."

Of course, there are other things you can do to protect your mind from succumbing to dementia. Pay attention to risk factors and exercise your brain, suggests my colleague Sarah Baldauf. And after a study published in March found that having excess belly fat at midlife may increase your risk for dementia, I recommended ways to get rid of extra weight around your midsection.

—January W. Payne