NSAIDs in the prevention of dementia: a Cache-22?

摘要

Multiple epidemiologic studies have reported an association between the use of nonstcroidal anti-inflammatory drugs (NSAIDs) and a reduced risk of Alzheimer disease (AD). In a recent meta-analysis,1 use of non-aspirin NSAIDs was associated with a 26% risk reduction of AD, with an even greater reduction (RR = 0.42; 95% CI 0.26 to 0.66) if NSAID use was sustained for at least 2 years. In vitro and in vivo animal studies also suggest that certain NSAIDs lower amyloid-beta-42 (AJ3-42) peptide levels independent of anti-inflammatory, cyclo-oxygenase-mediated effects. Despite these encouraging epidemiologic and laboratory data, randomized controlled trials of various NSAIDs have failed to demonstrate a significant effect on the rate of cognitive decline in patients with AD or on the rate of conversion to AD in patients with mild cognitive impairment. Furthermore, the eagerly awaited AD Anti-inflammatory Prevention Trial (ADAPT) using naproxen or celecoxib was terminated in December 2004 over concerns about cardiovascular risks.