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White Matter Degeneration in Huntington's Disease: A Study of Brain Structure and Cognition

Crawford, HE; (2016) White Matter Degeneration in Huntington's Disease: A Study of Brain Structure and Cognition. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterised by devastating physical, behavioural and mental dysfunction. Accumulating evidence indicates that abnormal white matter (WM) is a major hallmark of the disease, with both macro- and microstructural changes apparent before manifest diagnosis. This thesis is an investigation of WM in HD and uses various imaging and cognitive techniques to address some key challenges. Firstly, the development of reliable structural measurement techniques sensitive to longitudinal change may aid characterisation of subtle abnormalities before disease onset. Secondly, optimised diffusion imaging techniques which incorporate superior image processing tools will further understanding as to why changes are harder to find in the premanifest stage and will increase sensitivity to detect them. Thirdly, the development of novel, hypothesis-driven neuropsychological tasks will help detect heterogeneous cognitive decline in individuals in the earliest disease stages. To address these challenges, firstly, a novel corpus callosum (CC) segmentation technique is developed and applied to a large clinical cohort revealing disease-related reduction in baseline CC volume and elevated rates of change over 24 months in both premanifest and manifest HD participants. Secondly, an investigation of template effects in diffusion image analysis reveals consistency between analyses using three customised templates and evidence of the superiority of tensor-based registration over scalar-based registration is demonstrated. An exploratory investigation into the association between brain volume and WM diffusivity is also presented and disease-specific changes in HD gene-carriers are reported. Lastly, two specially designed, pathology-targeted cognitive tasks are applied to a premanifest HD cohort. Abnormal interhemispheric transfer from the non-dominant to dominant hemisphere as well as altered attentional processing and impaired automaticity is revealed. By developing techniques to characterise WM pathology and explore cognitive deficits, this thesis improves our understanding of the role of WM degeneration in the premanifest and early stages of HD.

Type: Thesis (Doctoral)
Title: White Matter Degeneration in Huntington's Disease: A Study of Brain Structure and Cognition
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: Huntington's disease, white matter
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: http://discovery.ucl.ac.uk/id/eprint/1532103
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