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.There is compelling evidence from laboratory research in animal model and cell culture systems, observational epidemiological studies, and small clinical trials that lowering cholesterol may reduce the pathology of Alzheimer's disease (AD). This is a clinical trial of simvastatin, a HMG CoA reductase inhibitor, the most commonly used class of lipid lowering agents, to reduce the clinical progression of Alzheimer's disease. The following evidence supports this hypothesis and is the basis for this study.Based on data accrued from observational studies, and that derived in the laboratory, we hypothesize that simvastatin will significantly reduce the clinical progression of AD as measured by the ADAScog. We also hypothesize that those who use simvastatin will show beneficial effects over placebo on measures of activities of daily living, psychiatric and behavioral symptoms, quality of life and economic measures. To study these hypotheses, we propose to recruit a cohort of 400 subjects with AD who do not have hypercholesterolemia.
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