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Brain structure and function in Huntington's disease gene carriers far from predicted disease onset

Zeun, Paul David; (2021) Brain structure and function in Huntington's disease gene carriers far from predicted disease onset. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Whilst there are currently no available disease modifying therapies for Huntington’s Disease (HD), recent progress in huntingtin-lowering strategies hold great promise. Initiating therapies early in the disease course will be important and a complete characterisation of the premanifest period will help inform when to initiate disease modifying therapies and the biomarkers that may be useful in such trials. Previous research has characterised the premanifest period up to approximately 15 years from predicted onset, but even at this early stage the disease process is already underway as evidenced by striatal and white matter atrophy, reductions in structural connectivity within brain networks, rising biofluid biomarkers of neuronal dysfunction, elevations in psychiatric symptoms and emerging subtle cognitive impairments. In order to understand how early neurodegeneration can be detected and which measures are most sensitive to the early disease processes, we need to look even earlier in the disease course. This thesis documents the recruitment and analysis of the HD Young Adult Study: a premanifest cohort further from predicted clinical onset than previously studied with an average of 24 years prior to predicted onset. Differences between gene carriers and controls were examined across a range of imaging, cognitive, neuropsychiatric and biofluid measures. The structural and functional brain connectivity in this cohort is then investigated in further detail. By providing a detailed characterisation of brain structure and function in the early premanifest period along with the most sensitive biomarkers at this stage, this work will inform future treatment strategies that may seek to delay the onset of functional impairments in HD.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Brain structure and function in Huntington's disease gene carriers far from predicted disease onset
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
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
URI: https://discovery.ucl.ac.uk/id/eprint/10123005
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