Effects of Atorvastatin on Cerebral Blood Flow in Middle-Aged Adults at Risk for Alzheimer’s Disease: A Pilot Study

Cynthia      M. Carlsson; Guofan      Xu; Zhifei      Wen; Jodi      H. Barnet; Hanna      M. Blazel; Richard      J. Chappell; James      H. Stein; Sanjay      Asthana; Mark      A. Sager; David      C. Alsop; Howard      A. Rowley; Sean      B. Fain; Sterling      C. Johnson

doi:10.2174/156720512803251075

Abstract

Background/Aims: Hypercholesterolemia in midlife increases risk for Alzheimer’s disease (AD) and contributes to cerebrovascular dysregulation - an early finding in preclinical AD pathology. Statins improve vascular reactivity, but it is unknown if they increase regional cerebral blood flow (CBF) in individuals at risk for AD. Methods: In a randomized, controlled, double-blind pilot study, 16 asymptomatic middle-aged adults with parental history of AD were randomized to atorvastatin or placebo daily for 4 months. At baseline and month 4, regional CBF was measured using arterial spin-labeling magnetic resonance imaging and endothelial function was measured using brachial artery ultrasound. Results: At baseline, participants with low HDL-cholesterol, higher global vascular risk, and greater endothelial dysfunction had reduced regional CBF in areas of the brain related to memory and learning (all p<0.03). Using voxel-based analysis, 4 months of atorvastatin increased CBF in bilateral hippocampi, fusiform gyrus, putamen and insular cortices compared to placebo. Conclusion: In this pilot study, atorvastatin increased regional CBF in persons at risk for AD. Further research is warranted to confirm whether statins increase CBF in areas of the brain related to memory and learning and whether such perfusion changes are associated with a delay in the onset of AD. Clinical Trial Registration: http://clinicaltrials.gov Identifier: NCT00751907.

Keywords: Alzheimer’s disease, cerebral blood flow, dementia, MRI perfusion, prevention, statins, FMD, aspartate aminotransferase