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No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.

Tuesday,2012-11-06 12:09 America/Los_Angeles — eenright
TitleNo advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.
Publication TypeJournal Article
Year of Publication2008
AuthorsSzekely, CA, Green, RC, Breitner, JCS, stbye, TØ, Beiser, AS, Corrada, MM, Dodge, HH, Ganguli, M, Kawas, CH, Kuller, LH, Psaty, BM, Resnick, SM, Wolf, PA, Zonderman, AB, Welsh-Bohmer, KA, Zandi, PP
JournalNeurology
Volume70
Issue24
Pagination2291-8
Date Published2008 Jun 10
ISSN1526-632X
KeywordsAcetaminophen, Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Cohort Studies, Female, Humans, Male, Middle Aged, Neuroprotective Agents, Peptide Fragments, Proportional Hazards Models, Prospective Studies, Risk Factors
Abstract<p><b>INTRODUCTION: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1212/01.wnl.0000313933.17796.f6
Alternate JournalNeurology
PubMed ID18509093
PubMed Central IDPMC2755238
Grant ListN01-HC25195 / HC / NHLBI NIH HHS / United States
K01 AG023014-01 / AG / NIA NIH HHS / United States
K24-AG022035 / AG / NIA NIH HHS / United States
R01 AG011380-13S1 / AG / NIA NIH HHS / United States
R01-AG15928 / AG / NIA NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
K01 AG023014-04 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
R01 AG016495 / AG / NIA NIH HHS / United States
U01-HL080295 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
AG13846 / AG / NIA NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 AG011380-12 / AG / NIA NIH HHS / United States
R01-AG85477 / AG / NIA NIH HHS / United States
R01 AG011380-07 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 AG015928-02 / AG / NIA NIH HHS / United States
R01-AG08122 / AG / NIA NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
R01 AG011380-13 / AG / NIA NIH HHS / United States
U01 HL080295-03 / HL / NHLBI NIH HHS / United States
R01-AG11380 / AG / NIA NIH HHS / United States
K24 AG027841-01A1 / AG / NIA NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 AG009029-09 / AG / NIA NIH HHS / United States
R01 AG009556-07 / AG / NIA NIH HHS / United States
R01 AG009556-05 / AG / NIA NIH HHS / United States
K24 AG027841 / AG / NIA NIH HHS / United States
U01 HL080295-02 / HL / NHLBI NIH HHS / United States
R01 AG011380-10S1 / AG / NIA NIH HHS / United States
K01 AG023014-05 / AG / NIA NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 AG009556 / AG / NIA NIH HHS / United States
R01 AG009029 / AG / NIA NIH HHS / United States
R01 AG011380 / AG / NIA NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
R01 AG008122-07 / AG / NIA NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 AG008325-10 / AG / NIA NIH HHS / United States
K24 AG022035-01 / AG / NIA NIH HHS / United States
R01 AG009556-09 / AG / NIA NIH HHS / United States
R01 AG011380-12S1 / AG / NIA NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 AG009556-08 / AG / NIA NIH HHS / United States
R01-AG16495 / AG / NIA NIH HHS / United States
R01-AG-09556 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
R01-AG09029 / AG / NIA NIH HHS / United States
R01 AG011380-11 / AG / NIA NIH HHS / United States
R01 AG011380-11S1 / AG / NIA NIH HHS / United States
P30 AG013846-04 / AG / NIA NIH HHS / United States
R01-AG07562 / AG / NIA NIH HHS / United States
U01 HL080295-04 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 AG011380-09 / AG / NIA NIH HHS / United States
K24-AG027841 / AG / NIA NIH HHS / United States
R01 AG011380-08 / AG / NIA NIH HHS / United States
K01-AG023014 / AG / NIA NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
K01 AG023014-02 / AG / NIA NIH HHS / United States
R01 AG008325-11 / AG / NIA NIH HHS / United States
R01-AG08325 / AG / NIA NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
K01 AG023014-06 / AG / NIA NIH HHS / United States
K24 AG022035 / AG / NIA NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
U01 HL080295-01 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
K01 AG023014-03 / AG / NIA NIH HHS / United States
K01 AG023014 / AG / NIA NIH HHS / United States
R01 AG011380-10 / AG / NIA NIH HHS / United States
R01-HG02213 / HG / NHGRI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HG002213 / HG / NHGRI NIH HHS / United States
R01-AG88930 / AG / NIA NIH HHS / United States
Z01 AG000185-18 / / Intramural NIH HHS / United States
R01 AG011380-06 / AG / NIA NIH HHS / United States
R01 AG009556-06A2 / AG / NIA NIH HHS / United States

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