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


METHODS
Randomized, double-masked chemoprevention trial.


METHODS
Six US memory clinics.


METHODS
Men and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment.


METHODS
Celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively.


METHODS
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.
Martin
Barbara K
BK
Szekely
Christine
C
Brandt
Jason
J
Piantadosi
Steven
S
Breitner
John C S
JC
Craft
Suzanne
S
Evans
Denis
D
Green
Robert
R
Mullan
Michael
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D000068579:Celecoxib