Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib

Arch Neurol. 2008 Jul;65(7):896-905. doi: 10.1001/archneur.2008.65.7.nct70006. Epub 2008 May 12.


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.

Trial registration: NCT00007189.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Celecoxib
  • Cognition / drug effects*
  • Cognition / physiology
  • Cognition Disorders / drug therapy
  • Cognition Disorders / pathology
  • Cognition Disorders / psychology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Naproxen / adverse effects
  • Naproxen / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Sulfonamides
  • Naproxen
  • Celecoxib

Associated data