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

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)477-489
    Number of pages13
    JournalJournal of Huntington's disease
    Volume2
    Issue number4
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Huntington Disease
    Cognition
    Atrophy
    Globus Pallidus
    Putamen
    Nucleus Accumbens
    Basal Ganglia
    Thalamus
    Psychiatry
    Outcome Assessment (Health Care)
    Clinical Trials
    Brain
    Neuroimaging
    Signs and Symptoms
    Hippocampus
    Biomarkers
    Regression Analysis
    Research Personnel
    Magnetic Resonance Imaging
    Genes

    Keywords

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

    Cite this

    Aylward, E. H., Harrington, D. L., Mills, J. A., Nopoulos, P. C., Ross, C. A., Long, J. D., ... PREDICT-HD Investigators And Coordinators Of The Huntington Study Group (2013). Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. Journal of Huntington's disease, 2(4), 477-489. https://doi.org/10.3233/JHD-130076

    Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. / Aylward, Elizabeth H.; Harrington, Deborah L.; Mills, James A.; Nopoulos, Peggy C.; Ross, Christopher A.; Long, Jeffrey D.; Liu, Dawei; Westervelt, Holly K.; Paulsen, Jane S.; PREDICT-HD Investigators And Coordinators Of The Huntington Study Group.

    In: Journal of Huntington's disease, Vol. 2, No. 4, 2013, p. 477-489.

    Research output: Contribution to journalArticle

    Aylward, EH, Harrington, DL, Mills, JA, Nopoulos, PC, Ross, CA, Long, JD, Liu, D, Westervelt, HK, Paulsen, JS & PREDICT-HD Investigators And Coordinators Of The Huntington Study Group 2013, 'Regional atrophy associated with cognitive and motor function in prodromal Huntington disease', Journal of Huntington's disease, vol. 2, no. 4, pp. 477-489. https://doi.org/10.3233/JHD-130076
    Aylward, Elizabeth H. ; Harrington, Deborah L. ; Mills, James A. ; Nopoulos, Peggy C. ; Ross, Christopher A. ; Long, Jeffrey D. ; Liu, Dawei ; Westervelt, Holly K. ; Paulsen, Jane S. ; PREDICT-HD Investigators And Coordinators Of The Huntington Study Group. / Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. In: Journal of Huntington's disease. 2013 ; Vol. 2, No. 4. pp. 477-489.
    @article{015c635a853c4e839f257d697f06d222,
    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.",
    keywords = "Huntington disease, magnetic resonance imaging, cognitive, psychiatric, motor",
    author = "Aylward, {Elizabeth H.} and Harrington, {Deborah L.} and Mills, {James A.} and Nopoulos, {Peggy C.} and Ross, {Christopher A.} and Long, {Jeffrey D.} and Dawei Liu and Westervelt, {Holly K.} and Paulsen, {Jane S.} and {PREDICT-HD Investigators And Coordinators Of The Huntington Study Group}",
    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.",
    year = "2013",
    doi = "10.3233/JHD-130076",
    language = "English",
    volume = "2",
    pages = "477--489",
    journal = "Journal of Huntington's disease",
    issn = "1879-6397",
    publisher = "IOS Press",
    number = "4",

    }

    TY - JOUR

    T1 - Regional atrophy associated with cognitive and motor function in prodromal Huntington disease

    AU - Aylward, Elizabeth H.

    AU - Harrington, Deborah L.

    AU - Mills, James A.

    AU - Nopoulos, Peggy C.

    AU - Ross, Christopher A.

    AU - Long, Jeffrey D.

    AU - Liu, Dawei

    AU - Westervelt, Holly K.

    AU - Paulsen, Jane S.

    AU - PREDICT-HD Investigators And Coordinators Of The Huntington Study Group

    N1 - 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.

    PY - 2013

    Y1 - 2013

    N2 - 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.

    AB - 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.

    KW - Huntington disease

    KW - magnetic resonance imaging

    KW - cognitive

    KW - psychiatric

    KW - motor

    U2 - 10.3233/JHD-130076

    DO - 10.3233/JHD-130076

    M3 - Article

    VL - 2

    SP - 477

    EP - 489

    JO - Journal of Huntington's disease

    JF - Journal of Huntington's disease

    SN - 1879-6397

    IS - 4

    ER -