title: Magnetic Resonance Imaging to assess carotid-brain interactions in people with stroke
Creators: name: Sneden, Fraser Neil
Publisher: name: University of Glasgow
Year: 2024

description: Carotid artery disease is a major risk factor for ischaemic stroke. It is associated with poorer functional outcomes, small vessel disease and may impact cognition. Allopurinol is a xanthine oxidase inhibitor that decreases serum uric acid levels. It is proposed that daily treatment of allopurinol may reduce oxidative stress and reduce carotid artery disease progression. The thesis aimed to address the relationship between carotid artery disease, brain imaging findings and cognitive function in people with ischaemic stroke. The thesis presents a systematic review of medical imaging studies investigating carotid artery disease and either brain imaging or cognitive function in ischaemic stroke (Chapter 3), before evaluating relationships between carotid artery disease and common vascular risk factors (Chapter 5) and brain structure, small vessel disease or post-stroke cognition (Chapter 6). Chapter 7 explored the potential treatment effects of longitudinal allopurinol on carotid artery disease and small vessel disease. Chapter 8 explored the use of a structural equation model in confirming the relationships between carotid artery disease, brain structure and post-stroke cognition.

Results from the systematic review I performed demonstrate that there is no overall standard for describing carotid artery disease. NASCET criteria are used to describe internal carotid artery stenosis, but often relationships between carotid structure and brain structure or cognition are under evaluated due to lack of reproducible standards in describing stroke populations. Moreover, univariate analysis between carotid artery measurements and common vascular risk factors found inconsistent relationships; no more than 3 common risk factors for stroke were related with a carotid artery measurement.

This thesis explored univariate and linear regression statistics for carotid artery disease and brain structure or cognition, finding a weak but positive relationship between common carotid intima-media thickness and WMH volume. Regression for common vascular risk factors found that age is a consistent covariant when evaluating the direction and strength of relationships between carotid structure and brain imaging findings. In a regression model, average vessel tortuosity was found to significantly relate to the WMH volume in the brain.

Described in the results from the longitudinal analyses, there was no significant difference between the treatment groups in the progression/regression of carotid artery stenosis, intima-media thickness, or vessel tortuosity. The data suggests that allopurinol does not influence carotid artery disease and may not act as a therapeutic agent for the reduction of stroke risk. WMH volume did not reduce significantly over the 2-year assessment period.

A structural equation modelling framework was proposed which aimed to describe carotid artery features and brain structure in separate variables. Though this framework did not reach significance, it is possible that more finetuning and exploratory analysis of vessel structure may provide a confirmatory model.

Overall, these data suggest that there should be more robust investigations into links between carotid artery disease and stroke, with attention to better reporting standards and greater longitudinal assessment.