Affiliations: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA | Department of Radiology, University of California, San Diego, La Jolla, CA, USA | VA San Diego Healthcare System, Research Service, San Diego, CA, USA | Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA | Departments of Psychiatry, Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD, USA | Division of Biology and Medicine, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA | Departments of Psychiatry, Neurology, Psychology and Neuroscience, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
Note:  Correspondence to: Jane S. Paulsen, Ph.D., The University of Iowa, 1-305 MEB, Iowa City, IA 52242, USA. Tel.: +1 319 353 4551; Fax: +1 319 353 4438; E-mail: firstname.lastname@example.org
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