Abstract
Growing evidence suggests that sleep plays a critical role in the development and progression of Alzheimer’s disease (AD). Population studies have shown that sleep problems increase the risk of AD dementia while animal and human studies have found disturbed sleep alters the production and clearance of AD pathology: amyloid-beta (Aβ) and tau. Furthermore, the natural history of AD is characterised by increasing sleep disturbance, raising the possibility that sleep may be a useful biomarker of disease progression. This thesis aimed to build on our understanding of the relationship between sleep and AD using a multi-method approach.The thesis presents an updated examination of the association between sleep disturbances and cognitive decline in the Caerphilly Prospective Study (CaPS). In this analysis, nocturnal limb movements strongly predicted vascular cognitive disorders but not non-vascular (AD) disorders. The AMyloid Protein Level Examination in relation to Sleep (AMPLESleep) study presents sleep data collected by actigraphy from cognitive clinic patients referred for a lumbar puncture to measure AD biomarkers. Increased sleep latency predicted lower Aβ42 and higher Tau/Aβ42 ratios, though the associations were attenuated after multivariable adjustment. The ContinUous behavioural Biomarkers Of cognitive Impairment (CUBOId) study was designed to investigate whether a home sensor system can detect behavioural changes in patients with AD dementia and mild cognitive impairment (MCI). The thesis presents five case studies recruited to CUBOId and includes their longitudinal cognitive data and sleep measurements collected by a wearable device. A longitudinal increase in total sleep time was found in two cases of MCI with AD pathology. In contrast, all sleep measures declined in another case of MCI without evidence of AD. Deteriorating sleep was observed in two dementia cases, though the models were consistent with chance. Overall, this thesis supports the growing consensus that sleep is relevant to our understanding of AD dementia.
Date of Award | 24 Jan 2023 |
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Original language | English |
Awarding Institution |
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Supervisor | E J Coulthard (Supervisor) & Yoav Ben-Shlomo (Supervisor) |
Keywords
- Alzheimer's disease
- Dementia
- Sleep