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Cognitive Function Over Time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a Randomized, Controlled Trial of Naproxen and Celecoxib
Open accessAbstract
BACKGROUND: Observational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs. OBJECTIVE: To evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults. DESIGN: Randomized, double-masked chemoprevention trial. SETTING: Six US memory clinics. PARTICIPANTS: Men and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment. INTERVENTIONS: Celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively. MAIN OUTCOME MEASURES: Seven tests of cognitive function and a global summary score measured annually. RESULTS: Longitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses. CONCLUSIONS: Use of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen.
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Considering the failure of prospective studies with NSAID treatment, the beneficial effects of NSAIDs is presumed to be related to pre-morbid function.
“Considering the failure of prospective studies with NSAID treatment (111), the beneficial effects of NSAIDs is presumed to be related to pre-morbid function.”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [111]
Long-term, large-scale population trials on NSAIDs for AD treatment have shown ibuprofen may have a protective effect on AD, while other NSAIDs seemingly do not.
“long-term, large-scale population trials on nonsteroidal anti-inflammatory drugs (NSAIDs) for AD treatment have shown that ibuprofen may have a protective effect on AD,509 while other NSAIDs seemingly do not.510”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [510]
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Metadata
- Authors
- ADAPT Research Group*
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- ADAPT Research Group*
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-07-01
- Volume
- 65
- Issue
- 7
- Pages
- 896
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2925195
- OpenAlex
- W1607135210
- Cited by
- 387
- References
- 20
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 9 · 2023: 8 · 2022: 19 · 2021: 15 · 2020: 18 · 2019: 15 · 2018: 9 · 2017: 18 · 2016: 24 · 2015: 25 · 2014: 29 · 2013: 18 · 2012: 34
- FWCI
- 28.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Abbott Laboratories
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Eisai
- National Institute on Aging (U01AG015477, U01-AG15477)
- 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
- Alzheimer's disease, cognitive function, naproxen, celecoxib, nonsteroidal anti-inflammatory drugs, chemoprevention, dementia prevention, older adults, cognitive decline, ADAPT trial
- MeSH terms
- Celecoxib, Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Cognition, Cognition Disorders, Double-Blind Method, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Naproxen, Pyrazoles, Sulfonamides, Time Factors, Treatment Outcome
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