Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jun 10;70(24):2291-8.
doi: 10.1212/01.wnl.0000313933.17796.f6. Epub 2008 May 28.

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

C A Szekely  1 , R C Green, J C S Breitner, T Østbye, A S Beiser, M M Corrada, H H 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
Affiliations

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

C A Szekely et al. Neurology. .

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 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.

PubMed Disclaimer

Conflict of interest statement

Disclosure: Dr. Welsh-Bohmer has a royalty interest in several patents on use of NSAIDs as a prevention/treatment for AD. No other conflicts of interest.

Figures

Figure 1
Figure 1. Forest plot of NSAID use and AD
NSAID=non-steroidal anti-inflammatory drug, aHR=adjusted hazard ratio, CI=confidence interval, AD=incident Alzheimer’s dementia, N=number; Black squares and horizontal lines represent each study’s risk estimate and 95% CI. The size of each square is indicative of the weight each study contributed to the meta-analysis; *aHRs result from a model adjusted for age, sex, and education; †Data analyzed using pooled study fixed-effects meta-analysis
Figure 2
Figure 2. Forest plot of NSAID use and AD by Aβ42-lowering capability
NSAID=non-steroidal anti-inflammatory drug, aHR=adjusted hazard ratio, CI=confidence interval, AD=incident Alzheimer’s dementia, N=number, SALA=selective Aβ42-lowering agent; Black squares and horizontal lines represent each study’s risk estimate and 95% CI. The size of each square is indicative of the weight each study contributed to the meta-analysis; *The aHRs result from one model including variables for any SALA (comparing risk among participants who took a SALA during follow-up vs. those who did not) and any non-SALA (comparing risk among participants who took a non-SALA during follow-up vs. those who did not), as well as adjusting for age, sex, and education; †Data analyzed using pooled study fixed-effects meta-analysis
See this image and copyright information in PMC

References

    1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimer's and Dementia. 2007;3:186–191. - PubMed
    1. Szekely CA, Thorne JE, Zandi PP, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology. 2004;23:159–169. - PubMed
    1. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997;48:626–632. - PubMed
    1. Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology. 2002 Sep 24;59:880–886. - PubMed
    1. Cornelius C, Fastbom J, Winblad B, Viitanen M. Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology. 2004 May;23:135–143. - PubMed

Publication types

MeSH terms

Grants and funding