title: Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study.
abstract: OBJECTIVE
  To quantify 18-month changes in white matter microstructure in premanifest (pre-HD) and symptomatic Huntington's disease (symp-HD). To investigate baseline clinical, cognitive and motor symptoms that are predictive of white matter microstructural change over 18months.
  
  
  METHODS
  Diffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18months. Unbiased tract-based spatial statistics (TBSS) methods were used to identify longitudinal changes in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) of white matter. Stepwise linear regression models were used to identify baseline clinical, cognitive, and motor measures that are predictive of longitudinal diffusion changes.
  
  
  RESULTS
  Symp-HD compared to controls showed 18-month reductions in FA in the corpus callosum and cingulum white matter. Symp-HD compared to pre-HD showed increased RD in the corpus callosum and striatal projection pathways. FA in the body, genu, and splenium of the corpus callosum was significantly associated with a baseline clinical motor measure (Unified Huntington's Disease Rating Scale: total motor scores: UHDRS-TMS) across both HD groups. This measure was also the only independent predictor of longitudinal decline in FA in all parts of the corpus callosum across both HD groups.
  
  
  CONCLUSIONS
  We provide direct evidence of longitudinal decline in white matter microstructure in symp-HD. Although pre-HD did not show longitudinal change, clinical symptoms and motor function predicted white matter microstructural changes for all gene positive subjects. These findings suggest that loss of axonal integrity is an early hallmark of neurodegenerative changes which are clinically relevant.
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia.
authors.forename: Govinda R
authors.initials: GR
authors.lastname: Poudel
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Domínguez D
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Calvary Health Care Bethlehem Hospital, Caulfield, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Churchyard
authors.affiliation: Department of Psychiatry, School of Clinical Sciences, Monash University, Victoria, Australia; Calvary Health Care Bethlehem Hospital, Caulfield, Victoria, Australia.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Chua
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; ARC Centre of Excellence for Integrative Brain Function, Monash University, Clayton, Victoria, Australia; VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: nellie.georgiou-karistianis@monash.edu.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
mesh_terms: D000328:Adult; D001315:Australia; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D062706:Prodromal Symptoms; D011597:Psychomotor Performance; D057190:Stroop Test; D066127:White Matter / Q000473:pathology*
keywords: Diffusion tensor imaging; Huntington's disease; Longitudinal DTI; TBSS