Journal
NEUROLOGY
Volume 70, Issue 24, Pages 2291-2298Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/01.wnl.0000313933.17796.f6
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Funding
- Intramural NIH HHS [Z01 AG000185-18] Funding Source: Medline
- NHGRI NIH HHS [R01-HG02213, R01 HG002213] Funding Source: Medline
- NHLBI NIH HHS [N01 HC085082, N01-HC-75150, N01-HC-85081, U01 HL080295-01, N01-HC-85080, N01 HC085081, N01-HC-85082, N01 HC085084, N01HC25195, U01-HL080295, N01 HC035129, N01 HC015103, N01HC55222, N01 HC075150, N01 HC085080, N01 HC055222, N01HC75150, N01 HC-55222, N01 HC045133, N01 HC085086, N01-HC-85079, U01 HL080295-03, N01-HC-85086, N01HC85086, N01 HC085083, U01 HL080295-02, N01 HC085079, N01HC85079, N01-HC-85083, N01 HC025195, N01-HC25195, U01 HL080295, U01 HL080295-04, N01 HC085085] Funding Source: Medline
- NIA NIH HHS [R01 AG011380-06, R01 AG009556-06A2, R01 AG009556-08, R01 AG011380-11S1, R01 AG009029-09, R01 AG011380-10, R01 AG008122-07, K01 AG023014-02, R01 AG008325-11, R01 AG011380-10S1, R01 AG016495, R01 AG011380-12S1, K01 AG023014-05, R01-AG85477, R01 AG009029, K01 AG023014-04, P30 AG013846, K24 AG022035, R01-AG15928, AG13846, R01 AG011380-13, K01 AG023014-03, R01 AG009556-09, R01 AG011380-12, R01-AG88930, R01 AG011380-11, R01-AG07562, R01-AG11380, R01-AG-09556, K24 AG027841-01A1, R01-AG09029, K01 AG023014, R01 AG011380-13S1, K01-AG023014, K24-AG027841, R01 AG008122, R01 AG011380-07, R01 AG015928-02, R01 AG009556, K01 AG023014-01, P30 AG013846-04, R01 AG011380, K01 AG023014-06, R01 AG011380-09, R01-AG08325, R01-AG16495, K24-AG022035, R01 AG009556-07, R01 AG008325-10, K24 AG027841, R01-AG08122, R01 AG015928, R01 AG011380-08, K24 AG022035-01, R01 AG009556-05] Funding Source: Medline
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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.
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