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Cognitive Control, Learning, and Clinical Motor Ratings Are Most Highly Associated with Basal Ganglia Brain Volumes in the Premanifest Huntington’s Disease Phenotype

Published online by Cambridge University Press:  16 February 2017

Maria B. Misiura ,
Spencer Lourens ,
Vince D. Calhoun ,
Jeffrey Long ,
Jeremy Bockholt ,
Hans Johnson ,
Ying Zhang ,
Jane S. Paulsen ,
Jessica A. Turner  and
Jingyu Liu Open the ORCID record for Jingyu Liu [Opens in a new window]
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Maria B. Misiura
Affiliation:
Department of Psychology, Georgia State University, Atlanta, Georgia
Spencer Lourens
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Vince D. Calhoun
Affiliation:
The Mind Research Network, Albuquerque, New Mexico Department of Electrical and Computer Engineering, The University of New Mexico, Albuquerque, New Mexico
Jeffrey Long
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Jeremy Bockholt
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Hans Johnson
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Ying Zhang
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Jane S. Paulsen*
Affiliation:
University of Iowa Carver College of Medicine, Iowa City, Iowa
Jessica A. Turner
Affiliation:
Department of Psychology, Georgia State University, Atlanta, Georgia
Jingyu Liu
Affiliation:
The Mind Research Network, Albuquerque, New Mexico
Betul Kara
Affiliation:
Department of Biology, Georgia State University, Atlanta, Georgia
Elizabeth Fall
Affiliation:
Department of Psychology, Georgia State University, Atlanta, Georgia
*
Correspondence and reprint requests to: Jane S. Paulsen,305 Medical Education Building, 200 Newton Road, Iowa City, IA 52242. E-mail:jane-paulsen@uiowa.edu
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Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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)

Keywords

Basal gangliaStriatumProdromal Huntington’s diseaseCaudateClusteringCluster analysisNeuropsychologyCognitionPsychiatric symptomsCognitive control
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 23 , Special Issue 2: Special Issue: Motor Cognition , February 2017 , pp. 159 - 170
Copyright
Copyright © The International Neuropsychological Society 2017 

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