Naproxen and celecoxib failed to prevent Alzheimer's disease in the first clinical trial to test the agents as preventives in older subjects who had no cognitive impairment, wrote Barbara K. Martin, Ph.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates.
Epidemiologic data suggest that prolonged NSAID use might protect against age-related cognitive decline, a possible forerunner of Alzheimer's disease, but small observational studies have yielded conflicting results.
The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), sponsored by the National Institute on Aging, was a placebo-controlled clinical trial designed to assess naproxen and celecoxib in 2,528 cognitively normal men and women aged 70 or older. A total of 726 were allocated to celecoxib, 719 to naproxen, and 1,083 to placebo. The study was halted early “after increased cardiovascular risk was observed with celecoxib in another prevention trial,” the investigators said (Arch. Neurol. 2008 May 12 [doi:10.1001/archneur.2008.65.7.nct70006]).
A total of 2,117 subjects contributed follow-up cognitive measures for at least 6 months after discontinuing the study medications.
Subjects' scores on the Modified Mini-Mental State Examination, a measure of global cognitive function, were significantly lower for both treatment groups than for the placebo group (−0.32 points for celecoxib and −0.36 points for naproxen), Dr. Martin and her associates said.
To put their findings in a clinical context, the researchers noted that the differences in cognitive scores between the treatment groups and the placebo group are equivalent to the average yearly decline among normal elderly subjects.