Naproxen for presymptomatic Alzheimer disease: Is this the end, or shall we try again?

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been hypothesized to play a protective role in Alzheimer disease (AD). This hypothesis is supported by a large number of cohort studies; a recent meta-analysis of 16 studies demonstrated that current or former NSAID use was associated with a reduced relative risk (RR) of AD (RR 0.81; 95% confidence interval 0.70–0.94).¹ A role for NSAIDs in AD is consistent with the increasing evidence that inflammatory activity plays a crucial role in AD pathogenesis.^2,3 In AD, protein complexes of β-amyloid and hyperphosporylated tau interact with microglia and astrocytes and result in the secretion of cytokines and chemokines, markers of inflammatory activation. Despite the observational epidemiologic data on the protective effect of NSAIDs and the evidence for a biologically plausible role of anti-inflammatory treatment, a large multiyear randomized placebo-controlled trial with naproxen and celecoxib (Alzheimer's Disease Anti-inflammatory Prevention Trial [ADAPT]) failed to support the hypothesis that either drug could delay the onset of AD in adults with a family history of dementia.⁴ While these initial results were disappointing, there was a suggestion of an effect among 3 of the cognitive subtests in the naproxen arm of this study,⁵ which led the investigators to design a subsequent naproxen trial, using a more sensitive outcome measure.

from Neurology recent issues http://bit.ly/2GSZhxi