Cohort Profile: the Oxford Parkinson's Disease Centre Discovery Cohort Magnetic Resonance Imaging sub-study (OPDC-MRI)

Purpose: The Oxford Parkinson9s Disease Centre (OPDC) Discovery Cohort magnetic resonance imaging (MRI) sub-study (OPDC-MRI) collects high quality multimodal brain MRI together with deep longitudinal clinical phenotyping in patients with Parkinson9s, at-risk individuals and healthy elderly participants. The primary aim is to detect pathological changes in brain structure and function, and develop, together with the clinical data, biomarkers to stratify, predict and chart progression in early-stage Parkinson9s and at-risk individuals. Participants: Participants are recruited from the OPDC Discovery Cohort, a prospective, longitudinal study. Baseline MRI data is currently available for 290 participants: 119 patients with early idiopathic Parkinson9s, 15 Parkinson9s patients with pathogenic mutations of the LRRK2 or GBA genes, 68 healthy controls and 87 individuals at risk of Parkinson9s (asymptomatic carriers of GBA mutation and patients with idiopathic rapid eye movement sleep behaviour disorder - RBD). Findings to date: Differences in brain structure in early Parkinson9s were found to be subtle, with small changes in the shape of the globus pallidus and evidence of alterations in microstructural integrity in the prefrontal cortex that correlated with performance on executive function tests. Brain function, as assayed with resting fMRI yielded more substantial differences, with basal ganglia connectivity reduced in early Parkinson9s, and RBD, but not Alzheimer9s, suggesting that the effect is pathology specific. Imaging of the substantia nigra with the more recent adoption of sequences sensitive to iron and neuromelanin content shows promising results in identifying early signs of Parkinsonian disease. Future plans: Ongoing studies include the integration of multimodal MRI measures to improve discrimination power. Follow-up clinical data are now accumulating and will allow us to correlate baseline imaging measures to clinical disease progression. Follow-up MRI scanning started in 2015 and is currently ongoing, providing the opportunity for future longitudinal imaging analyses with parallel clinical phenotyping.