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Cognitive and cerebral metabolic effects of celecoxib versus placebo in people with age-related memory loss: randomized controlled study.

Author(s): Small GW, Siddarth P, Silverman DH, Ercoli LM, Miller KJ, Lavretsky H, Bookheimer SY, Huang SC, Barrio JR, Phelps ME

Affiliation(s): 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

Publication date & source: 2008-12, Am J Geriatr Psychiatry., 16(12):999-1009.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

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. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial with 18-months of exposure to study medication. SETTING: University research institute. PARTICIPANTS: 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. INTERVENTIONS: Daily celecoxib dose of 200 or 400 mg, or placebo. MAIN OUTCOME MEASURES: 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.

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