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Randomized Controlled Trial
. 2011 Aug 9;77(6):556-63.
doi: 10.1212/WNL.0b013e318228bf11. Epub 2011 Jul 27.

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

M Sano  1 , K L Bell, D Galasko, J E Galvin, R G Thomas, C H van Dyck, P S Aisen
Affiliations
Randomized Controlled Trial

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

M Sano et al. Neurology. .

Abstract

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.

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Figures

Figure 1
Figure 1. Flow of participants
Figure 2
Figure 2. Effect of treatment on the primary outcome measures
Mean of ADAS-Cog = Alzheimer's Disease Assessment Scale–cognitive portion total score (A) and change score (B) by treatment and visit. Presented with 95% confidence intervals.
See this image and copyright information in PMC

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