Liu, Kathy Y.;
(2024)
The noradrenergic system and agitation in Alzheimer’s disease.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Aims: The thesis tests aspects of the hypothesis that Alzheimer’s disease (AD)-related neurodegeneration of the noradrenergic locus coeruleus (LC) contributes to agitation propensity through impaired emotion and autonomic regulation. Methods: After conducting a relevant systematic review, I used available measures from three pre-existing datasets to investigate proposed relationships between heart rate variability (HRV, an index of central autonomic regulation of heart rate), LC MRI contrast ratios (a putative marker of LC structural integrity), neural and/or behavioural measures of emotion regulation, and agitation in older adult and AD patient populations. The first study (ARIC) investigated HRV change in relation to agitation in AD dementia. The second (Cam-CAN) investigated the cross-sectional relationship between HRV and emotion regulation in cognitively healthy older adults, and whether LC integrity influenced this relationship. The third (DELCODE) investigated cross-sectional relationships between agitation, LC MRI contrast and emotion regulation indices in individuals with mild cognitive impairment or AD dementia. Results: Higher HRV was related to less successful cognitive reappraisal performance in cognitively healthy older adults (Cam-CAN) and higher agitation point prevalence in AD dementia individuals (ARIC). Agitation point prevalence was positively associated with a functional measure (and negatively with a corresponding structural measure) of emotion regulation network integrity, and agitation severity was positively related to LC MRI contrast (DELCODE). In cognitively healthy older adults, LC measures did not influence the HRV-emotion regulation relationship (Cam-CAN). Conclusions: Findings implicate the involvement of the LC and emotion and autonomic dysregulation in agitation in AD. A dissociation between structural and functional integrity and performance measures supports the presence of compensatory processes that may influence LC adaptive capacity in the face of neurodegeneration. Longitudinal and non-linear modelling approaches may clarify dynamic or causal relationships and the potential for HRV and LC MRI contrast to be markers of agitation propensity in AD.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The noradrenergic system and agitation in Alzheimer’s disease |
| 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. |
| 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 > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health Neuroscience UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10194755 |
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