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NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type.

TitleNSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type.
Publication TypeJournal Article
Year of Publication2008
AuthorsSzekely, CA, Breitner, JCS, Fitzpatrick, AL, Rea, TD, Psaty, BM, Kuller, LH, Zandi, PP
JournalNeurology
Volume70
Issue1
Pagination17-24
Date Published2008 Jan 01
ISSN1526-632X
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Apolipoproteins E, Cardiovascular System, Dementia, Female, Humans, Incidence, Male, Proportional Hazards Models, Prospective Studies, Risk Factors
Abstract<p><b>BACKGROUND: </b>Epidemiologic and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce risk of Alzheimer disease (AD). We therefore investigated the association between use of NSAIDs, aspirin, and the non-NSAID analgesic acetaminophen with incidence of dementia and AD.</p><p><b>METHODS: </b>Participants in the Cardiovascular Health Cognition Study included 3,229 individuals aged 65 or older, free of dementia at baseline, with information on medication use. We used Cox proportional hazards regression to estimate the association of medication use with incident all-cause dementia, AD, and vascular dementia (VaD). Additional analyses considered the NSAID-AD relationship as a function of age, presence of at least one epsilon 4 allele at APOE, race, and individual NSAIDs' reported ability to reduce production of the amyloid-beta peptide variant A beta(42).</p><p><b>RESULTS: </b>Use of NSAIDs was associated with a lower risk of dementia (adjusted hazard ratio or aHR 0.76, 95% CI or CI 0.60-0.96) and, in particular, AD (aHR 0.63, CI 0.45-0.88), but not VaD (aHR 0.92, CI 0.65-1.28). No similar trends were observed with acetaminophen (aHR 0.99, CI 0.79-1.24). Closer examination suggested AD risk reduction with NSAIDs only in participants having an APOE epsilon 4 allele (aHR 0.34, CI 0.18-0.65; aHR for others 0.88, CI 0.59-1.32). There was no advantage in AD risk reduction with NSAIDs reported to selectively reduce A beta(42).</p><p><b>CONCLUSIONS: </b>Results were consistent with previous cohort studies showing reduced risk of AD in NSAID users, but this association was found only in those with an APOE epsilon 4 allele, and there was no advantage for A beta(42)-lowering NSAIDs.</p>
DOI10.1212/01.wnl.0000284596.95156.48
Alternate JournalNeurology
PubMed ID18003940
PubMed Central IDPMC2877629
Grant ListU01-HL080295 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
U01 HL080295-01 / HL / NHLBI NIH HHS / United States
R01-AG15928 / AG / NIA NIH HHS / United States
R01-AG-09556 / AG / NIA NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01-AG-88930 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
R01 AG009556 / AG / NIA NIH HHS / United States