Clinical and neuroimaging biomarkers of early and prodromal Parkinson's disease

Thesis

The degeneration of the substantia nigra starts many years before the motor symptoms first emerge and the diagnosis of Parkinson’s disease (PD) can finally be made. Identification of patients at the early, prodromal, stage would provide insight into the earliest pathological pathways in PD and allow the targeted use of novel neuroprotective agents, slowing or even halting the progression of the disease. Patients with idiopathic REM sleep behaviour disorder (RBD) have been found to have a much higher risk of being diagnosed with PD, making them a promising group for studying prodromal PD. Resting-state functional MRI (rsfMRI) has previously shown promise as a biomarker in early PD. The overarching aim of the research presented in this DPhil thesis was to assess the utility of rs-fMRI as a biomarker in a group representative of prodromal PD. RBD was found to be a common and under recognised symptom in patients with early PD. Although no typical motor phenotype was identified, patients with both PD and RBD suffered more frequent and severe non-motor symptoms and had a more impaired quality of life. Patients with idiopathic RBD had mild motor symptoms and the full range of non-motor symptoms associated with PD. They were also found to have pattern of visual short term memory that mirrors that seen in idiopathic PD. Analysis of the basal ganglia network using rs-fMRI demonstrated marked abnormalities in patients with early PD, not seen in Alzheimer’s disease, where basal ganglia function is preserved. Patients with idiopathic RBD were indistinguishable from those with PD on rs-fMRI despite obvious differences on dopamine transporter single photon emission computerised tomography. The research presented in this DPhil thesis showed that basal ganglia connectivity, as measured using rs-fMRI, is a promising biomarker for the detection of early basal ganglia network dysfunction, and may help to identify patients at risk of developing PD in the future.

Authors: Rolinski, M

• DOI: 10.5287/ora-yrbvaqmag
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English