This project is designed to determine if the commonly used nonsteroidal anti-inflammatory drug (NSAID), celecoxib, is efficacious in delaying progression of cognitive symptoms in people with age-related cognitive losses who are at risk for developing AD. A total of 135 subjects with age-associated memory impairment (AAMI) who are at risk for further cognitive decline (age 40 to 90 years) will be randomized (double-blind design) to one of two treatment groups: celecoxib (400 mg/d) or placebo, and followed for 18 months. All randomized subjects will receive magnetic resonance imaging (MRI) scans, FDG PET scans, and selective genotyping (apolipoprotein E [APOE] and genetic risk for AD onset (e.g., APOE-4). Subjects receiving celecoxib are expected to show less evidence of cognitive decline than those receiving placebo. The proposed project builds upon our group's prior work on early detection of AD using brain imaging, genetic risk, and neuropsychological assessments. This project also is a logical follow-up to recent observational studies of a promising early intervention and will represent one of the first controlled, anti-inflammatory treatment trials for persons at high risk for age-related cognitive decline and the eventual development of AD.