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.
journal_name
Neurologyjournal_title
Neurologyauthors
Sano M,Bell KL,Galasko D,Galvin JE,Thomas RG,van Dyck CH,Aisen PSdoi
10.1212/WNL.0b013e318228bf11subject
Has Abstractpub_date
2011-08-09 00:00:00pages
556-63issue
6eissn
0028-3878issn
1526-632Xpii
WNL.0b013e318228bf11journal_volume
77pub_type
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