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Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease
Open accessAbstract
BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.
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“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 in t'Veld et al., 2001
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Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
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Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
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Metadata
- Authors
- in 't Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M. B., & Stricker, B. H. C.
- Affiliations
- Erasmus MC (NL)
- National Institutes of Health (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2001-11-22
- Volume
- 345
- Issue
- 21
- Pages
- 1515-1521
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2083556882
- Semantic Scholar
- 29c01ac52ec50618ec7b3b87ca55b707ca397434
- Cited by
- 1,196
- References
- 44
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 18 · 2023: 23 · 2022: 26 · 2021: 33 · 2020: 23 · 2019: 40 · 2018: 38 · 2017: 28 · 2016: 40 · 2015: 49 · 2014: 49 · 2013: 39 · 2012: 50
- FWCI
- 52.61
- Type
- journal article
- Language
- en
- Open access
- green
- pure.eur.nl
- Licence
- other-oa
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- nonsteroidal anti-inflammatory drugs, Alzheimer's disease, vascular dementia, dementia risk, long-term NSAID use, older adults
- MeSH terms
- Aged, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Prospective Studies, Risk, Salicylates, Dementia, Vascular, Cohort Studies, Proportional Hazards Models
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