This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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). These studies indicate that elevated cholesterol levels may be related to amyloid deposition and cognitive function and that lowering these levels may reduce amyloid and lead to cognitive benefit. Simvastatin is an HMG-CoA reductase inhibitor. In patients with coronary heart disease and hypercholesterolemia, it is indicated to reduce the risk 1) of total mortality by reducing coronary death, 2) of non-fatal myocardial infarction, 3) for undergoing myocardial revascularization procedures and 4) of stroke or transient ischemic attack. The hypothesis behind this study is that simvastatin will significantly reduce the clinical progression of AD and will show beneficial effects over placebo on measures of activities of daily living, psychiatric and behavioral symptoms, quality of life and economic measures. The population for this study will be 400 subjects with AD who do not have hypercholesterolemia.
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