+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Neurology 77(6): 556-563



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. To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. 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. 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. Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051230431

Download citation: RISBibTeXText

PMID: 21795660

DOI: 10.1212/wnl.0b013e318228bf11


Related references

Journal Club: a randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 79(4): E33-E36, 2012

Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial. Annals of Neurology 52(3): 346-350, 2002

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 85(16): 1383-1391, 2015

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial. Neurology 54(2): 295-301, 2000

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology 85(23): 2084-2084, 2015

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology 85(23): 2083-2084, 2015

DHEA treatment of Alzheimer's disease: A randomized, double-blind, placebo-controlled trial. Neurology 62(6): 1030, 2004

Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. Journal of Neural Transmission 109(7-8): 1089-1104, 2002

Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease. Geriatrics and Gerontology International 17(2): 211-218, 2017

Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. Journal of Clinical Psychopharmacology 28(1): 110-113, 2008

A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders 31(2): 158-164, 2011

H2 histamine receptor blockade in the treatment of Alzheimer disease: a randomized, double-blind, placebo-controlled trial of nizatidine. Alzheimer Disease and Associated Disorders 16(1): 24-30, 2002

Simvastatin as a novel therapeutic agent for venous ulcers: a randomized, double-blind, placebo-controlled trial. British Journal of Dermatology 170(5): 1151-1157, 2014

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study. American Journal of Psychiatry 157(10): 1686-1689, 2000

A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease. Journal of Clinical Psychiatry 73(6): 796-801, 2012