title: Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.
abstract: BACKGROUND
  Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD).
  
  
  OBJECTIVE
  Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures.
  
  
  METHODS
  Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD.
  
  
  RESULTS
  Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures.
  
  
  CONCLUSIONS
  Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.
authors: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
authors: Elizabeth H
authors: EH
authors: Aylward
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA VA San Diego Healthcare System, Research Service, San Diego, CA, USA.
authors: Deborah L
authors: DL
authors: Harrington
authors: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors: James A
authors: JA
authors: Mills
authors: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors: Peggy C
authors: PC
authors: Nopoulos
authors: Departments of Psychiatry, Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
authors: Christopher A
authors: CA
authors: Ross
authors: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors: Jeffrey D
authors: JD
authors: Long
authors: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors: Dawei
authors: D
authors: Liu
authors: Division of Biology and Medicine, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.
authors: Holly K
authors: HK
authors: Westervelt
authors: Departments of Psychiatry, Neurology, Psychology and Neuroscience, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors: Jane S
authors: JS
authors: Paulsen
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000473:pathology*; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D011597:Psychomotor Performance
keywords: Huntington disease; cognitive; magnetic resonance imaging; motor; psychiatric