5 June 2003. Both selective (COX-2 inhibitor, rofecoxib) and nonselective (COX-1/COX-2 inhibitor, naproxen) nonsteroidal antiinflammatory drugs (NSAIDs) fail to slow the cognitive decline associated with Alzheimer's disease (AD). This is the conclusion from a randomized controlled trial, which was reported in yesterday's Journal of the American Medical Association.
Paul Aisen of Georgetown University Medical Center, together with coworkers from the Alzheimer's Disease Cooperative Study, first brought this news to our attention at the 8th International Conference on Alzheimer’s Disease and Related Disorders in Stockholm last year (see ARF related news story). Aisen and colleagues recruited over 400 volunteers with mild to moderate AD and randomly assigned 351 of them to receive placebo, naproxen, or rofecoxib. Participants in the three groups were evaluated at baseline and at three-month intervals for up to a full year using the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale, which measures cognitive and motor skills. Volunteers were also given a battery of secondary assessments, including Neuropsychiatric Inventory (NPI), Alzheimer Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and the Quality of Life-AD (QOL-AD) tests.
Aisen and colleagues found that test scores among the three groups were not statistically different, but the trend in the rofecoxib group was toward greater cognitive decline (mean change in ADAS-Cog scores were -5.7, -5.8, and -7.7 for placebo, naproxen, and rofecoxib groups, respectively). In contrast, ADCS-ADL scores indicated some benefit from use of rofecoxib, but the authors suggest that this may be related to an analgesic effect-patients feeling better and being more active-rather than a direct effect on AD.
The authors also suggest that the failure to effect any benefit may be related to the doses used. Naproxen was given at a low dose because of concerns about undesirable side effects, though rofecoxib was given at the full antiinflammatory dose. The authors also caution that "these results do not address the efficacy of NSAIDs in the prevention of AD." ADAPT, the Alzheimer's Disease Antiinflammatory Prevention Trial (see ARF related news story), which hopes to determine if naproxen and another COX-2 inhibitor, celecoxib, can prevent progression of AD, is currently underway.-Tom Fagan.
Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression. JAMA. 2003 Jun 4;289(21):2819-26. Abstract