Cognitive and cerebral metabolic effects of celecoxib versus placebo in people with age-related memory loss: randomized controlled study.
OBJECTIVE
Because anti-inflammatory drugs may delay cognitive decline and influence brain metabolism in normal aging, the authors determined the effects of the cyclooxygenase-2 inhibitor, celecoxib, on cognitive performance and regional cerebral glucose metabolism in nondemented volunteers with mild age-related memory decline.


METHODS
Randomized, double-blind, placebo-controlled, parallel group trial with 18-months of exposure to study medication.


METHODS
University research institute.


METHODS
Eighty-eight subjects, aged 40-81 years (mean: 58.7, SD: 8.9 years) with mild self-reported memory complaints but normal memory performance scores were recruited from community physician referrals, media coverage, and advertising. Forty subjects completed the study.


METHODS
Daily celecoxib dose of 200 or 400 mg, or placebo.


METHODS
Standardized neuropsychological test battery and statistical parametric mapping (SPM) of FDG-PET scans performed during mental rest.


RESULTS
Measures of cognition showed significant between-group differences in executive functioning (F [1, 30] = 5.06, p = 0.03) and language/semantic memory (F [1, 31] = 6.19, p = 0.02), favoring the celecoxib group compared with the placebo group. Concomitantly, FDG-PET scans demonstrated bilateral metabolic increases in prefrontal cortex in the celecoxib group in the vicinity of Brodmann's areas 9 and 10, but not in the placebo group. SPM analyses of the PET data pooled by treatment arm corresponded to a 6% increase in activity over pretreatment levels (p <0.01, after adjustment for multiple comparisons).


CONCLUSIONS
These results suggest that daily celecoxib use may improve cognitive performance and increase regional brain metabolism in people with age-associated memory decline.
Small
Gary W
GW
Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu
Siddarth
Prabha
P
Silverman
Daniel H S
DH
Ercoli
Linda M
LM
Miller
Karen J
KJ
Lavretsky
Helen
H
Bookheimer
Susan Y
SY
Huang
S-C
SC
Barrio
Jorge R
JR
Phelps
Michael E
ME
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism; D000068579:Celecoxib; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053327:Apolipoprotein E4; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D000068579:Celecoxib