Veale, Thomas Daniel;
(2022)
Looking Below the Surface: The Role of Superficial White Matter in Alzheimer’s Disease.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Superficial white matter (SWM) contains short fibres and has largely been overlooked in Alzheimer’s disease (AD). Standard MRI approaches face confounding effects of complex fibre organisation and proximity to the cortex when measuring SWM in vivo. This thesis investigates SWM in AD by applying advanced MRI techniques to overcome these limitations. First, SWM in a cohort of young-onset AD and healthy controls was investigated using an advanced diffusion MRI model. Findings showed that young-onset AD participants have lower density, but increased dispersion, of SWM neurites compared to healthy controls. The second project found that these advanced diffusion MRI metrics are associated with independent quantitative MRI metrics sensitive to microstructure, and indicate previous findings are linked to losses in SWM myelin and iron. Project three explored the confounding effect of nearby CSF on cortical diffusion MRI measures and showed that a tissue-weighting approach can ameliorate CSF’s influence on regional averages. Project four investigated whether SWM is affected in autosomal dominant AD. Results supported earlier findings of lower density and higher dispersion of SWM neurites in symptomatic mutation carriers compared to non-carriers. Presymptomatic mutation carriers also had a lower density of neurites in entorhinal SWM. The final project used high-resolution 7T MRI to limit the influence of partial volume effects from nearby tissues on SWM measures in typical and atypical AD participants and healthy controls. An interim analysis qualitatively supports a loss of myelin and iron, with a potential increase in dispersion, occurring in the SWM during AD. In summary, SWM undergoes both degenerative and organisational changes during AD that coincide with a loss of iron. This extends the literature by overcoming limitations of standard MRI techniques previously used to investigate SWM in AD. SWM represents an overlooked region of brain changes in AD that may help detect and characterise the disease.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Looking Below the Surface: The Role of Superficial White Matter in Alzheimer’s Disease |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. 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 > 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 UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158366 |
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