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

C. A. Szekely, R. C. Green, J. C S Breitner, T. Østbye, A. S. Beiser, M. M. Corrada, Hiroko Dodge, M. Ganguli, C. H. Kawas, L. H. Kuller, B. M. Psaty, S. M. Resnick, P. A. Wolf, A. B. Zonderman, K. A. Welsh-Bohmer, P. P. Zandi

Research output: Contribution to journalArticle

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Abstract

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 Aβ 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 ncident 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 Aβ 42, suggesting that all conventiona NSAIDs including aspirin have a similar protective effect in humans.

Original languageEnglish (US)
Pages (from-to)2291-2298
Number of pages8
JournalNeurology
Volume70
Issue number24
DOIs
StatePublished - Jun 10 2008
Externally publishedYes

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Alzheimer Disease
Cohort Studies
Anti-Inflammatory Agents
Pharmaceutical Preparations
Aspirin
Non-Steroidal Anti-Inflammatory Agents
Risk Reduction Behavior
Acetaminophen
Drug Users
Observational Studies
Dementia
Prospective Studies
Incidence

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Szekely, C. A., Green, R. C., Breitner, J. C. S., Østbye, T., Beiser, A. S., Corrada, M. M., ... Zandi, P. P. (2008). No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology, 70(24), 2291-2298. https://doi.org/10.1212/01.wnl.0000313933.17796.f6

No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. / Szekely, C. A.; Green, R. C.; Breitner, J. C S; Østbye, T.; Beiser, A. S.; Corrada, M. M.; Dodge, Hiroko; Ganguli, M.; Kawas, C. H.; Kuller, L. H.; Psaty, B. M.; Resnick, S. M.; Wolf, P. A.; Zonderman, A. B.; Welsh-Bohmer, K. A.; Zandi, P. P.

In: Neurology, Vol. 70, No. 24, 10.06.2008, p. 2291-2298.

Research output: Contribution to journalArticle

Szekely, CA, Green, RC, Breitner, JCS, Østbye, T, Beiser, AS, Corrada, MM, Dodge, H, Ganguli, M, Kawas, CH, Kuller, LH, Psaty, BM, Resnick, SM, Wolf, PA, Zonderman, AB, Welsh-Bohmer, KA & Zandi, PP 2008, 'No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies', Neurology, vol. 70, no. 24, pp. 2291-2298. https://doi.org/10.1212/01.wnl.0000313933.17796.f6
Szekely CA, Green RC, Breitner JCS, Østbye T, Beiser AS, Corrada MM et al. No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology. 2008 Jun 10;70(24):2291-2298. https://doi.org/10.1212/01.wnl.0000313933.17796.f6
Szekely, C. A. ; Green, R. C. ; Breitner, J. C S ; Østbye, T. ; Beiser, A. S. ; Corrada, M. M. ; Dodge, Hiroko ; Ganguli, M. ; Kawas, C. H. ; Kuller, L. H. ; Psaty, B. M. ; Resnick, S. M. ; Wolf, P. A. ; Zonderman, A. B. ; Welsh-Bohmer, K. A. ; Zandi, P. P. / No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. In: Neurology. 2008 ; Vol. 70, No. 24. pp. 2291-2298.
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AU - Szekely, C. A.

AU - Green, R. C.

AU - Breitner, J. C S

AU - Østbye, T.

AU - Beiser, A. S.

AU - Corrada, M. M.

AU - Dodge, Hiroko

AU - Ganguli, M.

AU - Kawas, C. H.

AU - Kuller, L. H.

AU - Psaty, B. M.

AU - Resnick, S. M.

AU - Wolf, P. A.

AU - Zonderman, A. B.

AU - Welsh-Bohmer, K. A.

AU - Zandi, P. P.

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N2 - 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 Aβ 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 ncident 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 Aβ 42, suggesting that all conventiona NSAIDs including aspirin have a similar protective effect in humans.

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