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

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).