Abstract
Neurovascular factors are increasingly implicated in cognitive decline and dementia. However, in Parkinson’s disease –the fastest growing neurological condition worldwide– it remains unclear whether cognitive symptoms arise from disease specific neurovascular pathophysiology. This thesis combines multi-modal MRI with clinical and neuropsychological assessment to investigate the neurovascular basis of cognitive decline in Parkinson’s disease. Chapter 1 examines whether the standardised neuropsychological testing battery in Parkinson’s disease provides separable, function specific insights into cognitive health. Outcomes show that the battery captures global cognitive information but is not sensitive to domain specific functions. Chapter 3 uses 4D flow MRI to examine the anatomy and haemodynamics of the large vessels comprising the circle of Willis. Disrupted haemodynamics were observed in Parkinson’s disease, concurrent with evidence of vascular dilation. Chapter 5 uses pseudo-continuous arterial spin labelling MRI and builds upon chapter 3 by exploring the intersection of large and small vessel function. Altered large vessel haemodynamics in Parkinson’s disease corresponded with both altered microvascular haemoregulation, and region specific changes to capillary perfusion. Preliminary evidence was found to suggest that anti-parkinsonian levodopa medication may contribute to haemodynamic impairment. Chapter 7 uses structural MRI and builds upon previous chapters to explore the intersection of cerebral haemodynamics and neurolymphatic health (perivascular spaces). Changes to perivascular morphology co-occurred with altered arterial and venous function, as well as lower influx pressure, supporting the idea that haemodysregulation in Parkinson’s disease may compromise cerebral waste clearance. Collectively, compromised arterial and venous function, and alterations to neurolymphatic structures correspond with cognitive function, implicating sub-clinical haemodynamic changes in Parkinson’s cognitive decline and dementia. Findings are integrated with a systems perspective of vascular physiology to isolate candidate pathomechanisms of cognitive decline, and are discussed within the context of treatment potentials in Parkinson’s disease.