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Structural cortical grey matter changes during the transition from premanifest to manifest Huntington's disease: A methodological evaluation

Johnson, Eileanoir; (2018) Structural cortical grey matter changes during the transition from premanifest to manifest Huntington's disease: A methodological evaluation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Huntington’s disease (HD) is a genetic neurodegenerative disease characterised by motor, cognitive and psychiatric symptoms. Atrophy of subcortical brain structures has been well characterised and changes in the white matter are being mapped with increasing frequency, but structural changes in the cortex have been relatively overlooked in previous research. With recently trialled therapies specifically targeting the cortex, a better understanding of the pattern and progression of atrophy in this region should provide valuable measures for determining the impact of these novel treatments on the degenerative process. This thesis performs a methodological comparison aimed at optimising techniques to measure cortical characteristics in an HD cohort, and then applies the optimised techniques in a group of HD gene carriers undergoing conversion from pre-manifest HD to manifest HD quantifying cortical change during this critical period. Several tools for the quantification of cortical volume and cortical thickness are examined via detailed analyses using two datasets. This investigation results in a series of recommendations for the use of such tools, as well as the selection of the most appropriate measures for use in the second part of this thesis. In addition, since subcortical atrophy measures are widely used in HD research, the performance of one of the segmentation tools was evaluated by comparison with manual segmentations of the caudate and putamen. Finally, a novel multivariate analysis method is applied, based on the principles of DCM, to measure the rate, timing and acceleration of cortical GM change in a subgroup of 49 motor converters from the TRACK-HD cohort. This cortical atrophy is then related both to the biological underpinning of the disease in terms of CAG length and also the behavioural presentation of motor and cognitive symptoms. These findings present the first detailed characterisation of cortical grey matter change in HD, and have important implications for the understanding of HD progression.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Structural cortical grey matter changes during the transition from premanifest to manifest Huntington's disease: A methodological evaluation
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10048599
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