Cited by 1,196Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsInflammatory mediators and NSAID effects

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Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease

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in 't Veld, Bas A., Ruitenberg, Annemieke, Hofman, Albert, Launer, Lenore J., van Duijn, Cornelia M., Stijnen, Theo, Breteler, Monique M.B., Stricker, Bruno H.C.·2001·New England Journal of Medicine

DOI 10.1056/nejmoa010178

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Abstract

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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“It is now well accepted, from epidemiological studies and meta-analyses thereof, that inhibition of these enzymes with NSAIDs significantly protects against the subsequent development of AD (McGeer et al. 1996; In 'T Veld et al. 2001; Etminan et al. 2003; Vlad et al. 2008).”
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Background
Narciclasine inhibits LPS-induced neuroinflammation by modulating the Akt/IKK/NF-κB and JNK signaling pathways
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“…distribution of the PBN protective effect is highly reminiscent of the specific neuropathological lesions observed in AD and Parkinson’s disease and is supportive of recent observations of the efficacy of antioxidants in these diseases (Floyd and Carney 1996; Floyd et al. 2000; Veld et al. 2001).”
Background
Nonsteroidal anti-inflammatory drugs and Alzheimer disease: what's next?
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Self-citation
Pan-PPAR Modulation Effectively Protects APP/PS1 Mice from Amyloid Deposition and Cognitive Deficits
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Trans-cinnamaldehyde improves neuroinflammation-mediated NMDA receptor dysfunction and memory deficits through blocking NF-κB pathway in presenilin1/2 conditional double knockout mice
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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)
ORCID: Launer, Lenore J.
Stijnen, Theo
Breteler, Monique M.B.
Stricker, Bruno H.C.
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
DOI: 10.1056/nejmoa010178
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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Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease

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