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

Abstract Purpose The Oxford Parkinson’s 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 Parkinson’s, 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 Parkinson’s 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 Parkinson’s, 15 Parkinson’s patients with pathogenic mutations of the LRRK2 or GBA genes, 68 healthy controls and 87 individuals at risk of Parkinson’s (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 Parkinson’s 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 Parkinson’s, and RBD, but not Alzheimer’s, 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. Article Summary Strengths and limitations of this study High quality 3T MRI data in a very well phenotyped and longitudinally followed cohort of Parkinson’s and RBD. All imaging data were acquired on the same MRI scanner, quite unique for a study of this duration. The protocol includes both standard sequences, comparable across other studies, and sequences acquired to investigate study-specific research questions. Clinical longitudinal data are acquired every 18 months and will be used to relate baseline imaging with clinical progression. Information about conversion to Parkinson’s of the at-risk individuals will also be available, providing the ultimate validation of potential biomarkers. MRI follow-up is also ongoing, which will allow longitudinal imaging analyses. Statistical maps of published results and support data relative to the analyses are available to share. OPDC-MRI phenotyping is deep and relatively frequent, however the size of the cohort is not at the level of population-level cohort studies. MRI sequences are high quality, but could not exploit the latest advances in the field in order to maintain continuity.