MONDAY, May 12 (HealthDay News) -- Contrary to prior studies, a new trial shows that daily use of two popular pain-relieving drugs, Celebrex and naproxen, does not prevent cognitive decline in people with a family history of Alzheimer's disease.
In fact, naproxen, which goes under the brand names Aleve and Naprosyn, may even have a deleterious effect on cognitive function, the study found.
"The drugs we studied did not seem to improve cognitive function and, if anything, there was some weak evidence for a detrimental effect," said Barbara Martin, an investigator on the trial and assistant professor of epidemiology at the Johns Hopkins School of Public Health in Baltimore. "So we don't at this time recommend taking NSAIDs for the purpose of preventing Alzheimer's or cognitive decline."
Added Dr. John Morris, director of the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis and a member of the medical and scientific advisory council for the Alzheimer's Association: "My strong recommendation is I would not take any drug for a hoped-for effect until it has been demonstrated to have such an effect. Drugs potentially have side effects and unless there's a documented benefit, just because it's popular, I wouldn't rush to do that."
Both Celebrex and naproxen belong to the class of pain-killing drugs known as non-steroidal anti-inflammatory drugs (NSAIDs).
The study, to be published in the July issue of Archives of Neurology, was funded by the U.S. National Institute on Aging. The drug maker Pfizer provided the supply of Celebrex used in the study, plus a matching placebo, while Bayer Healthcare provided naproxen and a matching placebo.
Inflammatory processes may play a role in Alzheimer's disease and in cognitive decline in general.
"In addition to the plaques and tangles which are pathological hallmarks of Alzheimer's, there also seem to be signs of inflammation in the brains of people with the disease," Martin said.
That observation has led scientists to speculate that anti-inflammatory drugs may have an effect on the disease and, in fact, some previous observational studies have shown an association between NSAID use and a reduced risk of developing Alzheimer's.
In May 2007, the same group of researchers published findings that Celebrex and naproxen did not prevent Alzheimer's disease.
For the new study, 2,117 men and women over the age of 70 with a family history of Alzheimer's disease were randomly assigned to receive 200 milligrams of Celebrex twice a day, 220 milligrams of naproxen twice a day, or a placebo. Participants did not have a diagnosis of Alzheimer's, other dementias or mild cognitive impairment at the March 2001, start of the trial.
The participants' cognitive function was tested annually, but therapy was stopped in December 2004 because another study had reported an increased risk of cardiovascular problems in people taking Celebrex.
Analysis of this trial found that people taking naproxen had lower overall scores on measures of cognitive function than did men and women taking the placebo. Individuals taking naproxen or Celebrex had lower scores on a specific mental exam than did those taking a placebo.
The differences in results between this trial and previous research may have to do with the design of the study, or the results here may apply only to Celebrex and naproxen and not to other anti-inflammatory drugs such as ibuprofen, the researchers said. Or NSAIDs may only confer protection when given much earlier.
"This is speculative but there is increasing evidence that it may be a matter of timing, so by the time older adults take these drugs, if there is a protective effect, it may be past that time," Morris explained.
At this point, however, experts don't know what the best time would be to start the drugs.
"Increasingly we see that if we're going to want to understand how the process of Alzheimer's disease begins in the brain, we cannot limit our studies simply to older adults," Morris said. "We have to begin to study people even in middle age because the disease process may have its origins decades before people actually develop it."
Dr. Gary Kennedy is director of geriatric psychiatry at Montefiore Medical Center in New York City. Regarding this particular area of anti-inflammatory research as it pertains to cognitive problems, he said, "It's not strike three, but it's strike two for sure. The inflammatory model was a reasonable shot to begin with, but it was a long shot. [Inflammation] may be a side effect."
There's more on cognitive decline at the Alzheimer's Association.
SOURCES: Barbara K. Martin, Ph.D., assistant professor, epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore; John Morris, M.D., professor, neurology and director, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis and member, medical and scientific advisory council, Alzheimer's Association; Gary J. Kennedy, M.D., director, geriatric psychiatry, Montefiore Medical Center, New York City; July 2008, Archives of Neurology