In the first NIH-funded, multicenter, placebo-controlled study of its kind, the Georgetown researchers set out to test the efficacy of low-dose naproxen (sold under the brand name Aleve®) and rofecoxib (sold under the name Vioxx®) in slowing cognitive decline in patients with mild-to-moderate AD. Abundant laboratory and epidemiological evidence pointed to these two drugs as potential effective therapeutic agents, given that inflammation is a key feature of AD.
Despite this encouraging body of evidence, neither drug held up under this new double-blinded, study. In the 351 patients enrolled in the 12-month study, placed either in the naproxen, rofecoxib, or placebo groups, neither active treatment had a beneficial effect on the mean change in score on the Alzheimer Disease Assessment Scale ? Cognitive subscale (ADAS-Cog). This test measures memory, attention, reasoning, language, orientation, and complex motor function. In fact, patients taking rofecoxib experienced more rapid cognitive decline than the naproxen and placebo groups.
"Based on this new research, these treatments cannot be recommended for use in clinical settings and should be suspended by any clinician who currently thinks NSAIDs stem the progression of AD," said Paul Aisen, M.D., Georgetown University professor of neurology and principal investigator of the study. "While the National Institute on Aging continues to explore the potential for NSAIDs to be effective preventive tools for AD, the fact remains that these results are not encouraging for those who are in need of an effective, immediate intervention."
In addition to observing ADAS-Cog scale scores, Dr. Aisen and his colleagues in the Alzheimer's Disease Cooperative Study Group examined the time interval from the baseline visit to attainment of one of five possible end points: death, institutionalization, increase in global clinical dementia rating, 15-point decline on the Alzheimer's Disease Cooperative Study activities of daily living scale, or four point decline on the ADAC-Cog scale.
Over the course of 12 months, 242 patients reached at least one end point, and regardless of whether people took naproxen, rofecoxib, or placebo, all patients attained an end point on the same time frame.
"With an aging American population, AD is poised to be one of the most trying, expensive, and disruptive public health issues on our horizon," said Dr. Aisen. "I'm disappointed that the promise of NSAIDs is not panning out, but remain hopeful that we will make inroads using other possible therapeutic options."
Alzheimer's Disease is a progressive neurological disorder that currently affects more than four million people. There is no known cure for AD. A disease associated with aging, the number of cases will continue to grow. According to the Alzheimer's Association, an estimated 14 million Americans will have AD by the middle of this century (2050) unless a cure or prevention is found.
This study was funded by the National Institute on Aging, one of the National Institutes of Health.
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis--or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.