Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial

Ann Neurol. 2002 Sep;52(3):346-50. doi: 10.1002/ana.10292.


In a randomized, placebo-controlled, double-blind study, we investigated whether statins alter cholesterol metabolites and reduce Abeta levels in the cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In post hoc analysis, simvastatin significantly decreased Abeta40 levels in the cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes were not observed in more severely affected patients.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol / blood*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Placebos
  • Simvastatin / therapeutic use*


  • Amyloid beta-Peptides
  • Anticholesteremic Agents
  • Peptide Fragments
  • Placebos
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Cholesterol
  • Simvastatin