title: Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease: a pilot study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  http://clinicaltrials.gov Identifier: NCT00751907.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. cmc@medicine.wisc.edu.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.forename: Guofan
authors.initials: G
authors.lastname: Xu
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Wen
authors.forename: Jodi H
authors.initials: JH
authors.lastname: Barnet
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Blazel
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Chappell
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
authors.forename: David C
authors.initials: DC
authors.lastname: Alsop
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.forename: Sean B
authors.initials: SB
authors.lastname: Fain
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology / Q000517:prevention & control*; D000069059:Atorvastatin; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin