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

Lawton, M; Ben-Shlomo, Y; May, MT; Baig, F; Barber, TR; Klein, JC; Swallow, DMA; ... Hu, MTM; + view all (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. 10.1136/jnnp-2018-318337. Green open access

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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 (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.

Type: Article
Title: Developing and validating Parkinson's disease subtypes and their motor and cognitive progression
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2018-318337
Publisher version: http://dx.doi.org/10.1136/jnnp-2018-318337
Language: English
Additional information: Open access: This is an Open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10053982
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