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Cohort profile: the Oxford Parkinson’s Disease Centre Discovery Cohort MRI substudy (OPDC-MRI)

Abstract:

Purpose: The Oxford Parkinson’s Disease Centre (OPDC) Discovery Cohort MRI substudy (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 are currently available for 290 participants: 119 patients with early idiopathic Parkinson’s, 15 Parkinson’s patients with pathogenic mutations of the leucine-rich repeat kinase 2 or glucocerebrosidase (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’sand RBD. 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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/bmjopen-2019-034110

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-0540-9353
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author


More from this funder
Funder identifier:
https://ror.org/02417p338
Grant:
K-1404
More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
203139/Z/16/Z
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/L023784/2


Publisher:
BMJ Publishing Group
Journal:
BMJ Open More from this journal
Volume:
10
Issue:
8
Article number:
e034110
Publication date:
2020-08-13
Acceptance date:
2020-06-07
DOI:
EISSN:
2044-6055
ISSN:
2044-6055


Language:
English
Keywords:
Pubs id:
1110668
Local pid:
pubs:1110668
Deposit date:
2020-06-08

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