A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease.

Author(s): Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS

Affiliation(s): Mount Sinai School of Medicine, Bronx, NY 10468, USA. mary.sano@mssm.edu

Publication date & source: 2011-08-09, Neurology., 77(6):556-63. Epub 2011 Jul 27.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

BACKGROUND: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. OBJECTIVE: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. METHODS: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. RESULTS: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. CONCLUSION: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog.