Imaging Cognitive Impairment in Parkinson's Disease: The Role of Dopamine, Beta-Amyloid and Intrinsic Brain Networks

Parkinson's disease is a devastating neurodegenerative disorder with an immense impact on daily life. It is now known that the majority of PD patients undergo cognitive decline in addition to the motor symptoms of the disease. PD patients with mild cognitive impairment can experience cognitive deficits in memory, executive function, attention, language or visuospatial function, and are at an increased risk of progressing to dementia. Therefore, it is of interest to investigate the underlying brain changes occurring in these patients experiencing cognitive decline. The dopaminergic systems of the brain are affected in PD, and dysfunction of these systems may underlie cognitive impairment. Striatal dopamine depletion can extend beyond the motor regions of the striatum to regions involved in cognition and the modulation of cortico-striatal loops involved in cognitive processing. Mesocortical dopamine is released throughout the cortex and limbic regions, and dopamine in these regions binds to dopamine receptors that act to modulate neuronal activity during cognitive processes such as executive control and memory retrieval. Changes in mesocortical dopamine or cortical dopamine receptors could have an impact of cognitive performance in PD. Furthermore, there is evidence that amyloid deposition may be linked to cognitive decline in PD. Amyloid has been shown to impact functional connectivity of brain networks involved in executing large-scale cognitive processes. Thus, amyloid in PD may disrupt functional connectivity within or between cortical brain networks, affecting cognition. The aim of the work in this thesis was to 1) investigate the role of striatal and mesocortical dopamine dysfunction in contributing to executive and memory dysfunction in PD patients with mild cognitive impairment 2) investigate whether amyloid deposition in PD impacts functional connectivity of intrinsic brain networks and cognition.Ph.D