Govinda R Poudel1, Julie C Stout2, Juan F Domínguez D2, Andrew Churchyard3, Phyllis Chua4, Gary F Egan5, Nellie Georgiou-Karistianis6. 1. 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. 2. School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. 3. School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Calvary Health Care Bethlehem Hospital, Caulfield, Victoria, Australia. 4. Department of Psychiatry, School of Clinical Sciences, Monash University, Victoria, Australia; Calvary Health Care Bethlehem Hospital, Caulfield, Victoria, Australia. 5. 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. 6. School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: nellie.georgiou-karistianis@monash.edu.
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. METHOD: 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.
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. METHOD: 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: Vincent Pozorski; Jennifer M Oh; Nagesh Adluru; Andrew P Merluzzi; Frances Theisen; Ozioma Okonkwo; Amy Barzgari; Stephanie Krislov; Jitka Sojkova; Barbara B Bendlin; Sterling C Johnson; Andrew L Alexander; Catherine L Gallagher Journal: Hum Brain Mapp Date: 2018-06-27 Impact factor: 5.038
Authors: Joseph J Shaffer; Ali Ghayoor; Jeffrey D Long; Regina Eun-Young Kim; Spencer Lourens; Lauren J O'Donnell; Carl-Fredrik Westin; Yogesh Rathi; Vincent Magnotta; Jane S Paulsen; Hans J Johnson Journal: Hum Brain Mapp Date: 2017-01-03 Impact factor: 5.038
Authors: Rodolfo G Gatto; Allen Q Ye; Luis Colon-Perez; Thomas H Mareci; Anna Lysakowski; Steven D Price; Scott T Brady; Muge Karaman; Gerardo Morfini; Richard L Magin Journal: MAGMA Date: 2019-02-15 Impact factor: 2.310
Authors: Deborah L Harrington; Jeffrey D Long; Sally Durgerian; Lyla Mourany; Katherine Koenig; Aaron Bonner-Jackson; Jane S Paulsen; Stephen M Rao Journal: Mov Disord Date: 2016-09-13 Impact factor: 10.338
Authors: M Okan Irfanoglu; Amritha Nayak; Jeffrey Jenkins; Elizabeth B Hutchinson; Neda Sadeghi; Cibu P Thomas; Carlo Pierpaoli Journal: Neuroimage Date: 2016-02-28 Impact factor: 6.556