TY - JOUR
T1 - Regional atrophy associated with cognitive and motor function in prodromal huntington disease
AU - The PREDICT-HD Investigators and Coordinators of the Huntington Study Group
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 - Cross, Stephen
AU - Ryan, Patricia
AU - Epping, Eric A.
AU - Chiu, Edmond
AU - Preston, Joy
AU - Goh, Anita
AU - Antonopoulos, Stephanie
AU - Loi, Samantha
AU - Raymond, Lynn
AU - Decolongon, Joji
AU - Fan, Mannie
AU - Coleman, Allison
AU - Mallonee, William M.
AU - Suter, Greg
AU - Varvaris, Mark
AU - Yoritomo, Nadine
AU - McCusker, Elizabeth
AU - Griffith, Jane
AU - Loy, Clement
AU - Gunn, David
AU - Guttman, Mark
AU - Sheinberg, Alanna
AU - Law, Albie
AU - Quaid, Kimberly
AU - Wesson, Melissa
AU - Wojcieszek, Joanne
AU - Perlmutter, Joel
AU - Barton, Stacey
AU - Smith, Shineeka
AU - Barker, Roger A.
AU - Mason, Sarah
AU - Guzman, Natalie Valle
AU - Perlman, Susan
AU - Clemente, Brian
AU - Jones, Randi
AU - Wood-Siverio, Cathy
AU - Factor, Stewart A.
AU - Samii, Ali
AU - Macaraeg, Alma
AU - Mazzoni, Pietro
AU - Hershey, Tamara
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 - Cognitive
KW - Huntington disease
KW - Magnetic resonance imaging
KW - Motor
KW - Psychiatric
UR - http://www.scopus.com/inward/record.url?scp=84906929865&partnerID=8YFLogxK
U2 - 10.3233/JHD-130076
DO - 10.3233/JHD-130076
M3 - Article
C2 - 25062732
AN - SCOPUS:84906929865
SN - 1879-6397
VL - 2
SP - 477
EP - 489
JO - Journal of Huntington's Disease
JF - Journal of Huntington's Disease
IS - 4
ER -