TY - JOUR T1 - No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. JF - Neurology Y1 - 2008 A1 - Szekely, C A A1 - Green, R C A1 - Breitner, J C S A1 - Østbye, T A1 - Beiser, A S A1 - Corrada, M M A1 - Dodge, H H A1 - Ganguli, M A1 - Kawas, C H A1 - Kuller, L H A1 - Psaty, B M A1 - Resnick, S M A1 - Wolf, P A A1 - Zonderman, A B A1 - Welsh-Bohmer, K A A1 - Zandi, P P KW - Acetaminophen KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Alzheimer Disease KW - Amyloid beta-Peptides KW - Analgesics, Non-Narcotic KW - Anti-Inflammatory Agents, Non-Steroidal KW - Aspirin KW - Cohort Studies KW - Female KW - Humans KW - Male KW - Middle Aged KW - Neuroprotective Agents KW - Peptide Fragments KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors AB -

INTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.

METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.

RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).

CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

VL - 70 IS - 24 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18509093?dopt=Abstract ER -