title: Longitudinal diffusion changes in prodromal and early HD: Evidence of white-matter tract deterioration.
abstract: Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD).
  
  
  
  As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models.
  
  
  
  Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected.
  
  
  
  This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460-1477, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiology, University of Iowa, Iowa City, Iowa.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Shaffer
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghayoor
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, Iowa.|Department of Biostatistics, University of Iowa, Iowa City, Iowa.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, Iowa.
authors.forename: Regina Eun-Young
authors.initials: RE
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Spencer
authors.initials: S
authors.lastname: Lourens
authors.affiliation: Department of Radiology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: O'Donnell
authors.affiliation: Department of Radiology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Westin
authors.affiliation: Department of Radiology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Rathi
authors.affiliation: Department of Radiology, University of Iowa, Iowa City, Iowa.|Department of Psychiatry, University of Iowa, Iowa City, Iowa.|Biomedical Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magnotta
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, Iowa.|Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Neuroscience, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa.|Department of Psychiatry, University of Iowa, Iowa City, Iowa.|Biomedical Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D016880:Anisotropy; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D062706:Prodromal Symptoms; D011699:Putamen / Q000000981:diagnostic imaging; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: Huntington disease; computer-assisted; diffusion magnetic resonance imaging; diffusion tractography; disease progression; image processing; multicenter study; prodromal; white matter