University of Wisconsin–Madison

Effects of Statins on Pathobiology of Alzheimer's Disease: Evaluating Simvastatin’s Potential Role in Therapy (ESPRIT) Trial

June 2005 to June 2009

The purpose of this study is to find out how a medication, named simvastatin, taken to lower cholesterol affects a substance in the blood called amyloid beta (Aβ-40 and Aβ-42). High amounts of Aβ-40 and Aβ-42 may be associated with a greater risk of developing Alzheimer's disease (AD). This prospective, randomized, placebo-controlled clinical trial is designed to determine whether administration of simvastatin favorably alters biomarkers associated with AD. The study will be performed in middle-aged adults at increased risk of developing AD. It is hypothesized that in middle-aged, non-demented, adult children of persons with AD, simvastatin therapy will beneficially affect 4 mechanisms thought to contribute to AD risk by: 1) lowering CSF Aβ levels, 2) decreasing plasma markers of central nervous system (CNS) cholesterol metabolism, 3) decreasing CSF and plasma inflammatory markers, and 4) improving cerebral blood flow.
MR Protocol: Quantitative cerebral perfusion imaging will be performed using the method of Newman et al. and cerebral blood volume (CBV) will be measured. The method is based on echo planar T2*-weighted MRI using a 1-minute infusion of gadolinium instead of a bolus. It is believed that the method has a signal-to-noise ratio (SNR) 3-5 times greater than that obtained by area-under-the-curve methods, with high accuracy over a wide range of arterial, tissue, and MRI conditions. The perfusion MRI will be performed at the time of recruitment (baseline) and during the 9 month visit. Other MRI scans include a 3 plane localizer, a sagittal T1 FSPGR (MCA localization), axial T2 FLAIR (to evaluate atrophy, stroke, and ischemic white matter volumes), and T1 IR FSE (used for ROI selection for perfusion analysis).

This project led by: Cynthia Carlsson, MD