Potential for protection

The anti-inflammatory drug ibuprofen might partially protect against Alzheimer’s disease, a new study finds. But researchers caution that the findings, gleaned from the medical records of U.S. veterans, need to be confirmed in a clinical trial pitting ibuprofen against other drugs or a placebo.

Researchers tapped into a huge database of veterans’ health records to determine whether taking nonsteroidal anti-inflammatory drugs, referred to as NSAIDs, affects the incidence of Alzheimer’s disease.

They found that nearly 50,000 veterans over age 55 were diagnosed with Alzheimer’s disease between October 1998 and September 2005. For comparison purposes, the team of researchers identified 200,000 veterans who didn’t develop Alzheimer’s disease. These patients were chosen as controls because they were similar to the patients with Alzheimer’s in age, in gender and by the location of their Veterans Affairs medical facility. Both groups had an average age of 74 years.

After examining the veterans’ drug prescription history, the team found that people who took ibuprofen for five years over the course of the study were about half as likely to develop Alzheimer’s as people who didn’t take it. The findings appear in the May 6 Neurology.

Ibuprofen is an NSAID that can be prescribed or sold over the counter as Advil or Motrin. Curiously, the NSAID naproxen, which is in the same family as ibuprofen, failed to show protection. Naproxen is sold as Aleve and Naprosen.

More than 20 previous studies had tested NSAIDs to gauge their effects against Alzheimer’s disease — with mixed results. Very few were clinical trials in which researchers randomly assigned people to get an NSAID or a placebo and then tracked their progress. A recent trial found that two NSAIDs, naproxen and celecoxib, had no preventive effect against Alzheimer’s disease.

No such clinical trials have yet tested ibuprofen’s ability to lower the risk of developing Alzheimer’s disease. Based on the new results, the drug would be a good candidate, study coauthor Steven Vlad and his team conclude.

Anti-inflammatory drugs have attracted attention because inflammatory cells show up in the accumulations of a small protein called amyloid-beta that litter the brains of Alzheimer’s patients, says Vlad, a rheumatologist at Boston University.

Also, some NSAIDs, including ibuprofen and indomethacin, seem to suppress amyloid-beta manufacture. But in this study, NSAIDs that suppress amyloid-beta formation, looked at as a group, didn’t appear to protect any better than those that don’t, Vlad says.

These findings fall short on one important count, says neuroscientist David Morgan of the University of South Florida in Tampa. “The temptation is to assume that NSAID use provided protection, but the opposite may be just as true,” he says. For example, people with a pro-inflammatory disposition who need NSAIDs to treat arthritis or other problems might also have a tendency to clear amyloid-beta from their brains, he says. “It could be that inflammation protects against Alzheimer’s disease,” he says.

On the other hand, Morgan says, ibuprofen might have hidden properties. “It could be that some NSAIDs work better than others,” he adds.