The purpose of this trial is to test the ability of the non-steroidal anti-inflammatory medications naproxen and celecoxib to delay or prevent the onset of AD and age-related cognitive decline.

Considerable evidence suggests that inflammation may play a role in the neurodegenerative process of Alzheimer's disease (AD), and the use of non-steroidal anti-inflammatory drugs may be associated with reduced occurrence of AD. ADAPT is a randomized trial that will test the ability of the non-steroidal anti-inflammatory medications naproxen and celecoxib to delay or prevent the onset of AD and age-related cognitive decline. This long-term trial will run for 5 to 7 years.

The study is sponsored by the National Institute on Aging and is being conducted at the Roskamp Institute in Tampa, FL; the Veterans Affairs Puget Sound Health Care System with the University of Washington, in Seattle, WA; Boston University School of Medicine, in Boston, MA; the Johns Hopkins Medical Institutions, in Baltimore, MD; Sun Health Research Institute, in Phoenix, AZ; and the University of Rochester, in Rochester, NY. At each of these six sites, the goal is the enroll approximately 700 men and women, totalling 2,625 participants. Participants must be 70 years of age or older, have a parent, brother, or sister who has, or had, serious age-related memory loss, senility, dementia, or Alzheimer's disease.

Participants will be asked to take an anti-inflammatory medication or placebo (inactive pill) twice daily. Before enrolling in the trial, participants will be asked to go to a study site for two medical evaluations. Once enrolled, they will need to go to a study site for a medical evaluation every six months and to participate in a telephone interview twice a year for an average of up to seven years of follow-up.

Inclusion Criteria:

• Aged 70 years or older.
• Family history of parent, brother, or sister who has, or had, serious age-related memory loss, senility, dementia, or Alzheimer's disease.
• Study partner available to provide information on the cognitive status of the participant and to assist with monitoring of trial medications, if needed.
• Sufficient fluency in written and spoken English to participate in study visits and neuropsychological testing.
• Willingness to limit use of the following for the duration of the study: vitamin E (at doses greater than 400 IU per day), non-aspirin NSAIDs, histamine H2 receptor antagonists (Tagamet, for example), corticosteroids, anti-inflammatory or analgesic doses of aspirin (greater than 81 mg per day), Ginkgo biloba extracts
• Ability and intention to participate in regular study visits, in the opinion of the study physician.
• Provision of informed consent.

Exclusion Criteria:

• History of peptic ulcer disease with bleeding or obstruction.
• Clinically significant liver or kidney disease.
• History of hypersensitivity to aspirin, ibuprofen, celecoxib, naproxen, or other NSAIDs.
• Use of anti-coagulant medication.
• Cognitive impairment or dementia.
• Current alcohol abuse or dependence