There is growing evidence from clinical, epidemiological and laboratory studies that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD). Based on this evidence we propose to conduct a double blind parallel group, placebo-controlled trial of lovastatin, a hydroxymethyul-glutaryl-(HMGA) CoA-reductase inhibitor that lowers plasma cholesterol and lipoprotein levels, in patients with AD. Patients will be assigned in a 1:1 ratio to receive drug (lovastatin dose: 40 mg/day) or identical placebo. Study duration will be 1 year followed by a 3-month washout period. The primary outcome measure will include ADCS-CGIC, Dependence Scale, MMSE, and Quality of Life-AD, ADCS pharmacoeconomic assessment, ADCS-ADL and the Neuropsychiatric Inventory. Apo E genotype will be done on all subjects. Biomarkers to assess the relationship between treatment response and, amyloid metabolism and inflammation will e assayed on a subst (N=100) of subjects. We will store samples for possible analysis of other, yet to be identified inflammatory and oxidative stress markers for the brain. To power the trial to detect a 33% difference. ADAScog decline (80% power, alpha=0.05, dropout estimate 20%), we will enroll a total of 300 subjects.
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