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

doi:10.3233/JHD-130076

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 journal › Article › peer-review

52 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 language	English
Pages (from-to)	477-489
Number of pages	13
Journal	Journal of Huntington's disease
Volume	2
Issue number	4
DOIs	https://doi.org/10.3233/JHD-130076
Publication status	Published - 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.

Keywords

Huntington disease
magnetic resonance imaging
cognitive
psychiatric
motor

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Cite this

Aylward, E. H., Harrington, D. L., Mills, J. A., Nopoulos, P. C., Ross, C. A., Long, J. D., Liu, D., Westervelt, H. K., Paulsen, J. S., & 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

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

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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{\textquoteright}s Disease (HD) [5R01NS054893], 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington{\textquoteright}s [1U01NS082086], Functional Connectivity in Premanifest Huntington{\textquoteright}s Disease [1U01NS082083], and Basal Ganglia Shape Analysis and Circuitry in Huntington{\textquoteright}s Disease [1U01NS082085]. Dr. Aylward{\textquoteright}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{\textquoteright}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

C2 - 25062732

SN - 1879-6397

VL - 2

SP - 477

EP - 489

JO - Journal of Huntington's disease

JF - Journal of Huntington's disease

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

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