Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study

Journal article


Poudel, Govinda R., Stout, Julie C., Dominguez, Juan F., Churchyard, Andrew, Chua, Phyllis, Egan, Gary F. and Georgiou-Karistianis, Nellie. (2015). Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study. Neurobiology of Disease. 74(1), pp. 406 - 412. https://doi.org/10.1016/j.nbd.2014.12.009
AuthorsPoudel, Govinda R., Stout, Julie C., Dominguez, Juan F., Churchyard, Andrew, Chua, Phyllis, Egan, Gary F. and Georgiou-Karistianis, Nellie
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 18 months. Method: Diffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18 months. 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.

Keywordslongitudinal DTI; Huntington's disease; TBSS; diffusion tensor imaging
Year2015
JournalNeurobiology of Disease
Journal citation74 (1), pp. 406 - 412
PublisherAcademic Press
ISSN0969-9961
Digital Object Identifier (DOI)https://doi.org/10.1016/j.nbd.2014.12.009
Scopus EID2-s2.0-84937147028
Page range406 - 412
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Grant IDNHMRC/606650
Place of publicationUnited States of America
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