Regional atrophy associated with cognitive and motor function in prodromal Huntington disease

Elizabeth H. Aylward, Deborah L. Harrington, James A. Mills, Peggy C. Nopoulos, Christopher A. Ross, Jeffrey D. Long, Dawei Liu, Holly K. Westervelt, Jane S. Paulsen, PREDICT-HD Investigators And Coordinators Of The Huntington Study Group

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    52 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)477-489
    Number of pages13
    JournalJournal of Huntington's disease
    Issue number4
    Publication statusPublished - 2013

    Bibliographical note

    This research is supported by the National Institutes for Health, National Institute of Neurological Disorders and Stroke [5R01NS040068], CHDI Foundation, Inc [A3917], Cognitive and Functional Brain Changes in Preclinical Huntington’s Disease (HD) [5R01NS054893], 4D Shape Analysis for Modeling
    Spatiotemporal Change Trajectories in Huntington’s [1U01NS082086], Functional Connectivity in Premanifest Huntington’s Disease [1U01NS082083], and Basal Ganglia Shape Analysis and Circuitry in Huntington’s Disease [1U01NS082085]. Dr. Aylward’s work was partially supported by the National Institute of Child Health and Human Development [P30 HD02274].

    We thank the PREDICT-HD sites, the study participants, the National Research Roster for Huntington Disease Patients and Families, the Huntington’s Disease
    Society of America and the Huntington Study Group. This publication was supported by the National Center for Advancing Translational Sciences, and the
    National Institutes of Health (NIH), through Grant 2 UL1 TR000442-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.


    • Huntington disease
    • magnetic resonance imaging
    • cognitive
    • psychiatric
    • motor


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