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Lookup NU author(s): Professor David BurnORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. Objectives: To use a data-driven approach to determine the existence and natural history of subtypes of Parkinson's disease (PD) using two large independent cohorts of patients newly diagnosed with this condition. Methods: 1601 and 944 patients with idiopathic PD, 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 well-being 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 to 3.6) UPDRS III points per year while 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.
Author(s): Lawton M, Ben-Shlomo Y, May MT, Baig F, Barber TR, Klein JC, Swallow DMA, Malek N, Grosset KA, Bajaj N, Barker RA, Williams N, Burn DJ, Foltynie T, Morris HR, Wood NW, Grosset DG, Hu MTM
Publication type: Article
Publication status: Published
Journal: Journal of Neurology, Neurosurgery and Psychiatry
Year: 2018
Volume: 89
Issue: 12
Pages: 1279-1287
Print publication date: 01/12/2018
Online publication date: 25/07/2018
Acceptance date: 13/06/2018
Date deposited: 07/08/2018
ISSN (print): 0022-3050
ISSN (electronic): 1468-330X
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/jnnp-2018-318337
DOI: 10.1136/jnnp-2018-318337
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