Two-year double-masked trial of over-the-counter dosage of naproxen sodium vs placebo in 200 cognitively normal participants with a parental or multiplex first-degree family history Alzheimer's disease (AD) dementia. Primary outcomes are decline in cognitive function and slope of change in a summary Alzheimer Progression Score derived from serial assessment of neuroimaging, biochemical, and sensori-neural biomarker indicators of pre-clinical disease -- all believed likely to reflect progress of preclinical AD in this high risk cohort. Approximately 2/3 of participants have volunteered also for serial lumbar punctures for analysis of cerebrospinal fluid. A two-year off-treatment delayed-washout phase is planned to examine sustained treatment effects and evidence of disease modification.
Inclusion Criteria: * good physical health including normal hemoglobin and hematocrit * history or documentation of AD dementia in at least one parent, or in two siblings * cognitive performance without diagnosable deficit such as dementia, "mild cognitive impairment" * must have spouse or companion able to accompany participant for clinic visits * six or more years of formal education * fluent in either English or French * provision of informed consent Exclusion Criteria: * no current peptic ulcer disease * no history of prior peptic ulcer with bleed, perforation, intestinal obstruction * no major psychiatric disturbance * no regular use (4 or more doses per week) of aspirin, other non-steroidal anti-inflammatory drug (NSAID), opiate or other pain medication * no use, present or past, of acetylcholinesterase inhibitors or memantine * no regular use of vitamin E at dosage of 600 i.u. * no drug or alcohol dependence * no allergy to NSAIDs or sulfa antibiotics