Prosser, Lloyd;
(2024)
Investigating Imaging Biomarkers in Normal Ageing and Cognitive Impairment.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
All features of Alzheimer’s disease (AD), from symptom development, copathologies, and atrophy patterns, are heterogeneous. AD related biomarkers should be considered for their ability to reflect this heterogeneity, provide good early identification, and must be robust. This PhD will explore two domains; investigation of biomarkers’ ability to predict preclinical disease and heterogeneity, and improvement of current measures that reflect these biomarkers. To look at early predictions of cognitive impairment, two projects were completed. The survival analysis project showed that hippocampal volume is a strong predictor of clinical decline in both controls and those with mild cognitive impairment (MCI). In controls, white matter hyperintensites (WMH) were predictive of decline, suggesting a more mixed or vascular disease affected population. The second project used a data driven approach named Subtype and Stage Inference (SuStaIn), and looked at biomarker staging in amyloid positive individuals. SuStaIn derived four distinct subtypes; mixed pathology, presumed vascular disease led, classical AD, and relatively healthy amyloid positives. This PhD also assessed improvements for measurements of amyloid, and neurodegeneration. A Support Vector Machine (SVM) project assessed a measurement of amyloid deposition that is not dependent on reference region selection. The SVM measure aligned well with cerebrospinal fluid (CSF) amyloid classification. An additional project assessed the feasibility of using T2-FLAIR to produce an atrophy metric, comparing it with other widely used atrophy measures. T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) atrophy was aligned with both indirect volume change and T1-weighted atrophy measures, and a modest improvement in precision to the mean when using a composite score. In summary, this PhD aimed to both understand early changes in preclinical stages, and has described improvements in metrics that would be of use in AD.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating Imaging Biomarkers in Normal Ageing and Cognitive Impairment |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. 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. |
| Keywords: | Alzheimer's Disease, Dementia, Neuroimaging, Biomarkers |
| 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10186116 |
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