Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial.
OBJECTIVE
To evaluate the efficacy and safety of naproxen and celecoxib for the primary prevention of Alzheimer disease (AD).


METHODS
Randomized, placebo-controlled, double-masked clinical trial conducted at six US dementia research clinics. Volunteers aged 70+ years, with cognitive screening scores above designated cut-offs and a family history of AD, were randomly assigned to celecoxib 200 mg BID, naproxen sodium 220 mg BID, or placebo. Enrollment began in early 2001. The main outcome measure was diagnosis of AD after randomization.


RESULTS
On December 17, 2004, treatments were suspended. Events while on treatment yielded hazard ratios vs placebo of 1.99 (95% CI 0.80 to 4.97; p = 0.14) for celecoxib and 2.35 (0.95 to 5.77; p = 0.06) for naproxen. Imperfect screening measures led to enrollment of 7 individuals with dementia and 46 others with milder cognitive syndromes. Their (prevalent) illness was detected at enrollment and diagnosed within 6 months following randomization. Secondary analyses that excluded the 7 cases of prevalent dementia showed increased hazard ratios for AD with both treatments. Neither treatment produced a notable effect on the incidence of milder cognitive syndromes.


CONCLUSIONS
These results do not support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at least within the early years after initiation of treatment. Masked long-term follow-up of these participants will be essential.
Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD 21224, USA.
Lyketsos
C G
CG
Breitner
J C S
JC
Green
R C
RC
Martin
B K
BK
Meinert
C
C
Piantadosi
S
S
Sabbagh
M
M
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects; D018579:Patient Selection; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D015983:Selection Bias; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D018697:Nootropic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D000068579:Celecoxib