title: Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial.
abstract: BACKGROUND
  Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease.
  
  
  OBJECTIVE
  To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD.
  
  
  METHODS
  Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications.
  
  
  METHODS
  Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium.
  
  
  METHODS
  Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled.
  
  
  METHODS
  Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo.
  
  
  METHODS
  The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death).
  
  
  RESULTS
  The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group.
  
  
  CONCLUSIONS
  The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. psa@georgetown.edu
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Schafer
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: Eric
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Davis
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Shelia
authors.initials: S
authors.lastname: Jin
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D016016:Proportional Hazards Models; D011451:Prostaglandin-Endoperoxide Synthases; D012044:Regression Analysis; D013450:Sulfones; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases