July 8, 2008
Long-term use of ibuprofen and certain other inflammation-fighting drugs commonly used for aches and pains was associated with a lower risk of Alzheimer's disease in one recent study. But other reports show that anti-inflammatory medications provide no benefits for the brain.
The drugs, known as nonsteroidal anti-inflammatory drugs, or Nsaids, are sold in pharmacies as Advil, Motrin, Aleve and other over-the-counter pain relievers. Other Nsaids like indomethacin and Celebrex are also sold by prescription to ease pain and inflammation. The findings appeared in Neurology, the medical journal of the American Academy of Neurology.
Previous studies have shown conflicting results on whether Nsaids help to prevent or slow the onset of Alzheimer's. While Nsaids can relieve inflammation, they can also carry dangerous side effects.
Scientists are interested in these drugs, because increasingly inflammation has been linked to major ills of aging, including heart disease and Alzheimer's. But more research will be needed before doctors can routinely recommend that someone pop an Advil or related drug daily to help stave off Alzheimer's and keep the mind sharp.
In one of the current studies, researchers identified nearly 50,000 American veterans ages 55 and older with Alzheimer's disease. They were compared with nearly 200,000 veterans who did not have dementia. The study examined over five years of data and looked at the use of several Nsaids, including ibuprofen. The veterans received medical care and prescriptions through the Veterans Administration Health Care system.
The researchers, from Boston University School of Medicine, found that people who specifically used ibuprofen for more than five years were more than 40 percent less likely to develop Alzheimer's disease. Results also showed that the longer ibuprofen was used, the lower the risk for dementia. In addition, people who used certain other Nsaids for more than five years were 25 percent less likely to develop Alzheimer's disease than those who did not take these drugs.
In addition to ibuprofen, other Nsaids like indomethacin may also have been associated with a lower Alzhiemer's risk. However, other anti-inflammatory drugs like celecoxib (Celebrex) and naproxen (Naprosyn, Aleve) did not show any impact on dementia risk.
"These results suggest that the effect may be due to specific Nsaids, rather than all Nsaids as a class," said study author Dr. Steven Vlad. "Some of these medications taken long term decrease the risk of Alzheimer's disease, but it's very dependent on the exact drugs used."
"It doesn't appear that all Nsaids decrease the risk at the same rate," Dr. Vlad added. "One reason ibuprofen may have come out so far ahead is that it is by far the most commonly used."
The study was an observational study and does not carry the weight of a randomized, placebo-controlled trial, which compares drugs with look-alike dummy pills. Observational studies are subject to "indication bias," which means that it might not be the Nsaid use that drove the lower risk of dementia. Rather, it could be something about the people who chose to use the Nsaids that was responsible for the lower rates of dementia observed.
Naproxen and Celebrex Study
In another study, a randomized trial, researchers looked at more than 2,000 people ages 70 and older who had a family history of Alzheimer's disease. All were mentally intact at the start of the study, known as the ADAPT, for Alzheimer's Disease Anti-Inflammatory Prevention Trial.
One group took the prescription anti-inflammatory Celebrex, known generically as celecoxib, at a dose of 200 milligrams twice a day. Another group took naproxen, sold in pharmacies as Aleve, Naprosyn and other brands, at a dose of 220 milligrams twice daily. A third group took a placebo pill.
The study lasted for more than three years, and the participants were given mental tests annually. The study was halted after Celebrex was linked to an increased risk of heart attacks.
Six months later after they stopped taking the medicines, those taking the Nsaids showed no benefits in terms of brain function. In fact, those taking naproxen may have even shown slightly more cognitive decline.
"The ADAPT cognitive function results through six months after study treatment cessation do not show a protective effect with the use of specific NSAIDs and may suggest that cognitive scores are lower," the authors wrote.
The findings are consistent with earlier reports showing mixed benefits from anti-inflammatory drugs. Last year, researchers likewise reported that popular pain and inflammation fighters like aspirin, naproxen (Aleve, Naprosyn) and celecoxib (Celebrex) did nothing to stave off memory loss in people who took them. [See the article, "Common Pain Relievers Do Not Prevent Alzheimer's Disease"]
Previous studies have shown conflicting results on whether Nsaids help to prevent or slow the onset of Alzheimer's. More research will be needed before doctors can routinely recommend that someone take an Advil a day to keep Alzheimer's at bay. Nsaids have side effects, including nausea, vomiting, constipation and gastric ulcer.
Anyone with Alzheimer's, or concerned about the disease, should consult their physician before using drugs like ibuprofen long-term.
Steven C. Vlad, M.D., Donald R. Miller Sc.D., Neil W. Kowall, M.D., David T. Felson, M.D.: "Protective Effects of NSAIDs on the Development of Alzheimer's Disease." Neurology, Volume 70, May 6, 2008, pages 1672-1677.
ADAPT Research Group: "Cogntive Function Over Time in the Alzheimer's Disease Anti-Inflamamtory Prevention Trial: Results of a Randomized, Controlled Trial of Naproxen and Celecoxib." Archives of Neurolog, July 2008; 65:(doi:10.1001/archneur.2008.65.7.nct70006)