The purpose of this study is to test the effect of ibuprofen on the levels of a number of different proteins (called biomarkers) in cerebrospinal fluid (CSF), blood, and urine to see whether ibuprofen can influence certain biomarkers associated with the progression of Alzheimer's Disease.

The hypothesis to be tested is that the possible role of ibuprofen in preventing AD can be detected in changes in biomarkers of AD.

Eligible participants will complete an enrollment visit to include: a physical exam, a neurological exam, neuropsychological testing, and a minor blood draw. At the second visit, approximately 2 weeks later, participants will undergo a baseline lumbar puncture, and will be issued either ibuprofen or placebo to take once daily for 6-12 weeks. Both the participants and the clinicians will be masked to treatment assignment. After 6-12 weeks, the participants will undergo a second, and final, lumbar puncture. This will complete participant involvement in the study.

• Drug: Ibuprofen
• Drug: Placebo

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Inclusion Criteria:

• Age 59 years or older at time of the first visit
• Family history of one or more first-degree relatives with Alzheimer-like dementia
• Fluency in written and spoken English
• Willingness to limit use of Vitamin E (<600 IU per day), Non-aspirin NSAIDs, Aspirin (<81mg per day), Histamine H2 receptor antagonists, and Gingko biloba extract for the duration of the study
• Ability and intention to participate in regular study visits
• Provision of informed consent

Exclusion Criteria:

• History of peptic ulcer disease complicated by perforation, hemorrhage or obstruction
• History of uncomplicated peptic ulcer with symptoms in the 28 days prior to the first visit
• Clinically significant hypertension, anemia, liver disease, or kidney disease
• Hypersensitivity to aspirin or other NSAIDS
• Concurrent use of warfarin, ticlopidine, or any other type of anti-coagulant
• Concurrent use of systemic corticosteroids
• Use of ≥ 4 doses per week of either of the following in the 14 days prior to the first visit: Non-aspirin NSAIDs, Aspirin (>81mg per day), or Histamine H2 receptor antagonists
• Current plasma creatinine ≥1.5mg/dL
• Enrollment in any trial that is likely to interfere with BONSAI procedures or affect treatment outcomes
• Cognitive impairment or dementia