Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression

Lawton, M. et al. (2018) Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression. Journal of Neurology, Neurosurgery and Psychiatry, 89(12), pp. 1279-1287. (doi: 10.1136/jnnp-2018-318337) (PMID:30464029) (PMCID:PMC6288789)

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Abstract

Objectives: To use a data-driven approach to determine the existence and natural history of subtypes of Parkinson’s Disease using two large independent cohorts of patients newly diagnosed with this condition. Methods: 1,601 and 944 idiopathic PD patients, from Tracking Parkinson’s and Discovery cohorts respectively, were evaluated in motor, cognitive and non-motor domains at the baseline assessment. Patients were recently diagnosed at entry (within 3.5 years of diagnosis) and were followed-up every 18 months. We used a factor analysis followed by a k-means cluster analysis, while prognosis was measured using random slope and intercept models. Results: We identified four clusters: (1) fast motor progression with symmetrical motor disease, poor olfaction, cognition and postural hypotension; (2) mild motor and non-motor disease with intermediate motor progression; (3) severe motor disease, poor psychological wellbeing and poor sleep with an intermediate motor progression; (4) slow motor progression with tremor-dominant, unilateral disease. Clusters were moderately to substantially stable across the two cohorts (kappa 0.58). Cluster 1 had the fastest motor progression in Tracking Parkinson’s at 3.2 (95% CI: 2.8-3.6) UPDRS III points per year whilst cluster 4 had the slowest at 0.6 (0.1-1.1). In Tracking Parkinson’s cluster 2 had the largest response to levodopa 36.3% and cluster 4 the lowest 28.8%. Conclusions: We have found four novel clusters that replicated well across two independent early PD cohorts and were associated with levodopa response and motor progression rates. This has potential implications for better understanding disease pathophysiology and the relevance of patient stratification in future clinical trials.

Item Type:Articles
Additional Information:The Oxford Discovery study was funded by the Monument Trust Discovery Award from Parkinson’s UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, and the NIHR Clinical Research Network: Thames Valley and South Midlands The Tracking Parkinson’s study was funded by Parkinson’s UK and supported by the National Institute for Health Research (NIHR) DeNDRoN network, the NIHR Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the NIHR funded Biomedical Research Centre in Cambridge.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Grosset, Dr Donald and Grosset, Dr Katherine
Authors: Lawton, M., Ben-Shlomo, Y., May, M. T., Baig, F., Barber, T. R., Klein, J. C., Swallow, D. M.A., Malek, N., Grosset, K. A., Bajaj, N., Barker, R. A., Williams, N., Burn, D. J., Foltynie, T., Morris, H. R., Wood, N. W., Grosset, D. G., and Hu, M. T.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Neurology, Neurosurgery and Psychiatry
Publisher:BMJ Publishing Group
ISSN:0022-3050
ISSN (Online):1468-330X
Published Online:25 July 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of Neurology, Neurosurgery and Psychiatry 89(12): 1279-1287
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
525044PROBAND: Parkinson's repository of biosamples and networked datasetsDonald GrossetParkinson's UK (PARKINSO)J-1101RI NEUROSCIENCE & PSYCHOLOGY