Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
Condition: Alzheimer's Disease; Aging
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Recent evidence suggests that there is a significant overlap between AD and cerebrovascular
      disease. In fact, AD and cerebrovascular disease may share some of the same risk factors,
      including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A
      reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up
      to 70%; however, effects differed by specific statin use. This study will compare two
      statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does
      not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD
      and inflammatory markers. The primary aim of the proposed study is to determine whether there
      is a reduction in Abeta with statins and whether the ability of the statin to cross the
      blood-brain barrier will affect its ability to decrease Abeta. If it can be demonstrated that
      statins alter AD-associated biomarkers, this would have broad implications for the treatment
      and prevention of AD.
    

Detailed description: 
      Recent evidence suggests that there is a significant overlap between AD and cerebrovascular
      disease. In fact, AD and cerebrovascular disease may share some of the same risk factors,
      including hypercholesterolemia. In addition, studies have suggested that the HMG Co-A
      reductase inhibitor lipid-lowering agents, known as "statins," decrease the risk of AD by up
      to 70%; however, effects differed by specific statin use. This study will compare two
      statins, simvastatin (which crosses the blood brain barrier) and pravastatin (which does
      not), with respect to their ability to alter blood and cerebrospinal fluid (CSF) levels of AD
      and inflammatory markers. The primary aim of the proposed study is to determine whether there
      is a reduction in Abeta with statins and whether the lipophilicity of the statin will affect
      its ability to decrease Abeta. In addition, the proposal will determine statin effects on
      both peripheral and central inflammation and whether the lipophilicity of the statin will
      affect its ability to decrease inflammation. If it can be demonstrated that statins alter
      AD-associated biomarkers, this would have broad implications for the treatment and prevention
      of AD.

      This study will be performed in 60 cognitively normal middle-aged and older persons with
      hypercholesterolemia (total cholesterol >200 and/or LDL>130), presumably persons that have a
      lipid-related increased risk of AD and in whom alterations of CSF Abeta can be
      interpreted.The differential effects of the two statins will be evaluated in a 12-week
      randomized treatment trial with 30 subjects in each group.

      Prior to randomization and following 12 weeks of treatment with simvastatin or pravastatin,
      subjects will undergo CSF and blood collection. In the CSF, concentrations of Abeta 1-40,
      Abeta 1-42, soluble APP, tau, 24S-hydroxycholesterol, apoE, total cholesterol,
      F2-isoprostanes, glucose, protein, and cell count will be measured. In the blood,
      concentrations of total cholesterol, HDL, LDL, triglyceride, phospholipids, fatty acids,
      24S-hydroxycholesterol, apoE, apoB, apoA1, Abeta 1-40, Abeta 1-42, F2-isoprostanes,
      C-reactive protein, fibrinogen, iron, homocysteine, and albumin will be measured. Plasma
      simvastatin and pravastatin concentrations will be measured at study completion. APOE
      genotyping will be performed.
    

Intervention name(s): simvastatin; pravastatin
Intervention type(s): Drug; Drug
Intervention description(s): simvastatin 40 mg tablets once per day for 12 weeks; pravastatin 80 mg tablets once per day for 12 weeks
Other intervention name(s): Zocor; Lipitor
Intervention MeSH terms: Simvastatin; Pravastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Alzheimer's disease; beta-amyloid; statins