title: Cognitive Control, Learning, and Clinical Motor Ratings Are Most Highly Associated with Basal Ganglia Brain Volumes in the Premanifest Huntington's Disease Phenotype.
abstract: Huntington's disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis.
  
  
  
  The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements.
  
  
  
  Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning.
  
  
  
  Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159-170).
authors.affiliation: 1Department of Psychology,Georgia State University,Atlanta,Georgia.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Misiura
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Spencer
authors.initials: S
authors.lastname: Lourens
authors.affiliation: 3The Mind Research Network,Albuquerque,New Mexico.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Long
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Bockholt
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Hans
authors.initials: H
authors.lastname: Johnson
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.affiliation: 1Department of Psychology,Georgia State University,Atlanta,Georgia.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
authors.affiliation: 3The Mind Research Network,Albuquerque,New Mexico.
authors.forename: Jingyu
authors.identifier: 0000-0002-1724-7523
authors.initials: J
authors.lastname: Liu
authors.affiliation: 5Department of Biology,Georgia State University,Atlanta,Georgia.
authors.forename: Betul
authors.initials: B
authors.lastname: Kara
authors.affiliation: 1Department of Psychology,Georgia State University,Atlanta,Georgia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fall
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000473:pathology*; D016000:Cluster Analysis; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007859:Learning Disabilities / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000502:physiology*; D009483:Neuropsychological Tests; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D000071058:Huntingtin Protein
keywords: Basal ganglia; Caudate; Cluster analysis; Clustering; Cognition; Cognitive control; Neuropsychology; Prodromal Huntington’s disease; Psychiatric symptoms; Striatum