Extended results of the Alzheimer's disease anti-inflammatory prevention trial
Document Type
Article
Abstract
Background: Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) delay onset of Alzheimer's dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID-assigned groups. Methods: We continued the double-masked ADAPT protocol for 2 additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF tau to Aβ 1-42. Results: Including 40 new events observed during follow-up of 2071 randomized individuals (92% of participants at treatment cessation), there were 72 AD cases. Overall, NSAID-related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with cognitive impairment - no dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees who were given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer-type neurodegeneration. Conclusions: These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies. © 2011 The Alzheimer's Association. All rights reserved.
Publication Date
7-1-2011
Publication Title
Alzheimer's and Dementia
ISSN
15525260
E-ISSN
15525279
Volume
7
Issue
4
First Page
402
Last Page
411
PubMed ID
21784351
Digital Object Identifier (DOI)
10.1016/j.jalz.2010.12.014
Recommended Citation
Breitner, John C.; Baker, Laura D.; Montine, Thomas J.; Meinert, Curtis L.; Lyketsos, Constantine G.; Ashe, Karen H.; Brandt, Jason; Craft, Suzanne; Evans, Denis E.; Green, Robert C.; Ismail, M. Saleem; Martin, Barbara K.; Mullan, Michael J.; Sabbagh, Marwan; and Tariot, Pierre N., "Extended results of the Alzheimer's disease anti-inflammatory prevention trial" (2011). Neurology. 877.
https://scholar.barrowneuro.org/neurology/877