May 10, 2007
Popular pain and inflammation fighters like aspirin and Aleve, promoted by some as a possible preventive against Alzheimer's disease, did nothing to stave off dementia or memory loss in those who took them, two new studies show. In one study, published in the medical journal Neurology, the over-the-counter remedy naproxen (Aleve, Naprosyn) and the prescription pain reliever celecoxib (Celebrex) did nothing to prevent Alzheimer's disease. The other study, from the British Medical Journal, found that aspirin did nothing to prevent memory loss in older women.
Earlier studies that observed large groups of people had suggested that long-term use of a medication known as an NSAID (non-steroidal anti-inflammatory drugs) might have benefits in the prevention of Alzheimer's disease because NSAIDs help to ease inflammation. Inflammation has been linked to heart disease and damage to blood vessels throughout the body, including the brain. The results of the current studies, involving aspirin, naproxen and celecoxib, however, suggest that these drugs do not prevent Alzheimer's or memory loss in old age, at least not within a three-year period following the start of treatment.
The most recent study, from the American Academy of Neurology's medical journal Neurology, involved more than 2,100 men and women over age 70 at six medical centers across the U.S. All had a family history of Alzheimer's disease, though none had major memory problems or other symptoms at the start of the study.
The participants were randomly assigned to get daily doses of naproxen, celecoxib, or a look-alike dummy drug (placebo) for up to four years. Most of the participants in the study took one of these drugs for less than two years.
The study found neither treatment was associated with a reduction in Alzheimer's disease or other forms of dementia. In fact, those who were taking an NSAID showed an increased risk of Alzheimer's disease, although the results were not statistically significant (in other words, the apparent risk might have been due to chance).
"Although our study was conducted to test the hypothesis that celecoxib or naproxen would reduce the incidence of Alzheimer's disease, these results indicate no such effect, at least within the first few years after treatment begins," said study author Constantine Lyketsos, MD, MHS, with Johns Hopkins Bayview Hospital and Johns Hopkins School of Medicine in Baltimore, Maryland.
The findings appear to be inconsistent with other studies suggesting reduced risk of Alzheimer's disease among people who take NSAIDs over a long period of time. "One possible explanation for this inconsistency is that our findings relate specifically to celecoxib and naproxen, but not to other commonly used NSAIDs, such as ibuprofen," said John C. S. Breitner, MD, with VA Puget Sound Health Care, another study author.
Another possibility, he suggests, is that these drugs may be ineffective in those who already have extensive damage to the brain, despite remaining symptom free. "The drugs may not prevent the progression of disease in people who have advanced Alzheimer's pathology without symptoms," he says, "the very people most likely to develop symptoms within a year or two." This study does not rule out the possibility that people who use NSAIDS for a longer period of time or earlier in life might benefit.
"While long-term follow-up of our study's participants is essential, for now we suggest celecoxib and naproxen not be taken to primarily prevent Alzheimer's disease," Dr. Lyketsos urges. "At the same time, we do not have sufficient evidence to suggest that persons at risk for Alzheimer's disease should avoid these or other NSAIDs when the medications are used for their approved indications."
British Aspirin Study
The previous week, researchers reported in the British Medical Journal that aspirin did not prevent memory loss and cognitive decline in older women. The women were part of the Women's Health Study, a large and ongoing study of the effects of long-term aspirin use on heart disease and cancer.
Researchers followed some 6,400 women aged 65 or older for about 10 years. Some were taking low-dose aspirin on a regular basis (in this case, every other day), a measure that is sometimes recommended for seniors to prevent heart disease. The others were not taking aspirin.
At the start of the study, all were in generally good health and did not have Alzheimer's or serious memory problems. The women were given extensive memory tests at two-year intervals, beginning about six years after they had entered the study.
The researchers found that older women who were taking aspirin did not perform better on memory and word recall tests. They did perform slightly better on category tests, in which they were asked to name as many animals as they could, for example, within a minute. However, these results were not statistically significant. The authors concluded that "other methods for preserving cognitive function in older people need to be investigated."
Both these studies suggest that anti-inflammatory drugs do not have a major impact on the onset of Alzheimer's disease or memory loss. However, aspirin and other medications can be effective against heart disease, strokes, and other ills.
ADAPT Research Group: "Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial." Neurology 2007, doi:10.1212/01.wnl.0000260269.93245.d2
Jae Hee Kang, Nancy Cook, JoAnn Manson, et al: "Low dose aspirin and cognitive function in the women's health study cognitive cohort." British Medical Journal, doi:10:1136/bmj.39166.BE (published 27 April 2007)