Cognitive and Cerebral Metabolic Effects of Celecoxib Versus Placebo in People With Age-Related Memory Loss: Randomized Controlled Study

• Published in: The American journal of geriatric psychiatry Vol. 16; no. 12; pp. 999 - 1009
• Main Authors: Small, Gary W., Siddarth, Prabha, Silverman, Daniel H.S., Ercoli, Linda M., Miller, Karen J., Lavretsky, Helen, Bookheimer, Susan Y., Huang, S-C, Barrio, Jorge R., Phelps, Michael E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.12.2008; Elsevier Limited
• Subjects: Adult; Age Factors; age-related memory complaints; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Apolipoprotein E4 - genetics; Apolipoprotein E4 - metabolism; Celecoxib; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cognition Disorders - drug therapy; Cognition Disorders - metabolism; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2 inhibitor; Double-Blind Method; Female; Fluorodeoxyglucose F18 - metabolism; Fluorodeoxyglucose F18 - pharmacology; Humans; Internal Medicine; Male; Memory Disorders - drug therapy; Memory Disorders - metabolism; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Radiopharmaceuticals; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Treatment Outcome; Cyclooxygenase-2 inhibitor; age-related memory complaints; positron emission tomography; celecoxib
• ISSN: 1064-7481; 1545-7214; 1545-7214
• DOI: 10.1097/JGP.0b013e31818cd3a4

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. Randomized, double-blind, placebo-controlled, parallel group trial with 18-months of exposure to study medication. University research institute. 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. Daily celecoxib dose of 200 or 400 mg, or placebo. Standardized neuropsychological test battery and statistical parametric mapping (SPM) of FDG-PET scans performed during mental rest. 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). These results suggest that daily celecoxib use may improve cognitive performance and increase regional brain metabolism in people with age-associated memory decline.