Risk of Alzheimer's disease and duration of NSAID use
Open accessAbstract
In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29) for those with less than 2 years of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.
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Long-term treatment with NSAIDs reduced the risk for AD, delayed disease onset, and slowed cognitive decline.
“The recognition that a robust inflammatory response contributes to AD also fuelled the discovery that long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the risk for AD, delayed disease onset, and slowed cognitive decline (McGeer et al., 1996;Stewart et al., 1997;in t' in t'Veld et al., 2001).”
From PPARγ/RXRα-Induced and CD36-Mediated Microglial Amyloid-β Phagocytosis Results in Cognitive Improvement in Amyloid Precursor Protein/Presenilin 1 Mice (2012) · cites this paper as Stewart et al., 1997
The Results report a lower risk of AD associated with NSAID use, particularly with two or more years of reported use. The Discussion describes delayed onset as a possible benefit requiring trials to establish protection; the paper does not report that NSAIDs slowed cognitive decline. The claim also presents an observed association as a treatment effect. (LLM, conf=0.88)
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- Authors
- Stewart, W. F., Kawas, C., Corrada, M., & Metter, E. J.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Neurology
- Published
- 1997-03
- Volume
- 48
- Issue
- 3
- Pages
- 626-632
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2163110760
- Cited by
- 1,132
- References
- 16
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 13 · 2023: 22 · 2022: 19 · 2021: 22 · 2020: 23 · 2019: 22 · 2018: 21 · 2017: 24 · 2016: 28 · 2015: 29 · 2014: 32 · 2013: 24 · 2012: 31
- FWCI
- 42.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- American Academy of Neurology
- National Institutes of Health
- National Institute on Aging (R01AG008325, R01-AG08325)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- Alzheimer's disease, nonsteroidal anti-inflammatory drugs, aspirin, paracetamol, medication use, neuroprotection, neuroinflammation
- MeSH terms
- Acetaminophen, Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Confidence Intervals, Risk Assessment
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