Cited by 402Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsInflammatory mediators and NSAID effects

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A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

on behalf of the Rofecoxib Protocol 078 study group, Thal, Leon J, Ferris, Steven H, Kirby, Louis, Block, Gilbert A, Lines, Christopher R, Yuen, Eric, Assaid, Christopher, Nessly, Michael L, Norman, Barbara A, Baranak, Christine C, Reines, Scott A·2005·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300690

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Abstract

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo (N=732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94), p=0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.

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Authors: on behalf of the Rofecoxib Protocol 078 study group, Thal, L. J., Ferris, S. H., Kirby, L., Block, G. A., Lines, C. R., Yuen, E., Assaid, C., Nessly, M. L., Norman, B. A., Baranak, C. C., & Reines, S. A.
Affiliations: University of California San Diego (US)
New York University (US)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author: Lines, Christopher R
ORCID: Ferris, Steven H
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2005-03-02
Volume: 30
Issue: 6
Pages: 1204-1215
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300690
OpenAlex: W2051776695
Cited by: 402
References: 51
Citations by year: 2026: 5 · 2025: 9 · 2024: 6 · 2023: 15 · 2022: 16 · 2021: 16 · 2020: 6 · 2019: 12 · 2018: 14 · 2017: 19 · 2016: 15 · 2015: 20 · 2014: 13 · 2013: 14 · 2012: 24
FWCI: 21.05
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: University of Rochester
Dartmouth College
Towson University
York University
University of Illinois at Urbana-Champaign
School of Medicine, New York University
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: rofecoxib, mild cognitive impairment, Alzheimer's disease, COX-2 inhibitors, COX-2 inhibition, disease progression, anti-inflammatory therapy
MeSH terms: Aged, Cognition Disorders, Dementia, Double-Blind Method, Female, Humans, Lactones, Male, Membrane Proteins, Neuropsychological Tests, Prostaglandin-Endoperoxide Synthases, Psychiatric Status Rating Scales, Sulfones, Cyclooxygenase Inhibitors, Disease Progression, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors

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A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

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