Verdi, Serena;
(2023)
Mapping Individual Differences in the Neuroanatomy of Dementia.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Dementia is a highly heterogeneous disorder, with marked individual differences in clinical presentation and neurobiology. Neuroanatomical normative modelling is an emerging statistical technique which captures individual-level variability across the brain by comparing individuals to a predetermined ‘normative’ distribution of a neuroimaging measure. This thesis presents the first application of neuroanatomical normative modelling to dementia. A previously curated large independent dataset (~33-58k) was used to measure the normative distribution of brain volume and cortical thicknesses within ~150 brain regions. Dementia patients were then compared to these regional models to ascertain how they differ, quantified using Z-scores. In this thesis, novel brain-wide maps of Z-scores are generated for dementia clinical groups and for individual patients. These Z-scores are also explored in relation to disease phenotypes and presenting symptoms in dementia – specifically, observations are made within patients with sporadic Alzheimer's Disease (AD), familial AD and people with mild cognitive impairment. The influence of AD disease progression on neuroanatomical heterogeneity was also explored using longitudinal data, and survival analyses were conducted that predicted progression from MCI to AD using Z-scores. Moreover, comparisons are made between different diseases and their presenting phenotypes. Furthermore, the relationship between amyloid and tau markers, genetic mutations and neuroanatomical heterogeneity are assessed. Together these studies present neuroanatomical normative modelling as a quantitative tool for measuring neuroanatomical variability in dementia, and highlight the differences in atrophy patterns between individual patients.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Mapping Individual Differences in the Neuroanatomy of Dementia |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. 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 > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10184369 |
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