A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease.
Neurology. 2011 Aug 9;77(6):556-63
Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS
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.
PMID: 21795660 [PubMed - indexed for MEDLINE]