This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.[from CRISP website (edited)]Given the evidence from epidemiological, animal, and clinical research suggesting that statins may have a preventive role in Alzheimer's disease (AD), this study proposes to evaluate the effect of simvastatin on cerebrospinal fluid (CSF) and plasma markers of AD progression, central nervous system (CNS) cholesterol metabolism, and CNS inflammation in a population of middle-aged adults at increased risk for developing AD. One-hundred (100) men and women who have a parent with AD will be recruited for this 9-month randomized, controlled trial evaluating the effects of simvastatin 80 mg nightly vs. placebo on biomarkers of (1) CSF amyloid beta-42 levels; (2) plasma markers of CNS cholesterol metabolism; (3) CSF and plasma markers of inflammation; and (4) MRI perfusion. Participants will have fasting labs drawn, CSF collected, cognitive testing done, and MRI scans done (in 50 of the subjects) at baseline and 9-month follow-up. Additional visits at 1, 3, and 6 months will assess side effects. Cognitive testing will also be repeated at the 3-month follow-up. Outcome measures at 9 months will be compared to baseline.
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