PT - JOURNAL ARTICLE AU - Michael Lawton AU - Yoav Ben-Shlomo AU - Margaret T May AU - Fahd Baig AU - Thomas R Barber AU - Johannes C Klein AU - Diane M A Swallow AU - Naveed Malek AU - Katherine A Grosset AU - Nin Bajaj AU - Roger A Barker AU - Nigel Williams AU - David J Burn AU - Thomas Foltynie AU - Huw R Morris AU - Nicholas W Wood AU - Donald G Grosset AU - Michele T M Hu TI - Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression AID - 10.1136/jnnp-2018-318337 DP - 2018 Dec 01 TA - Journal of Neurology, Neurosurgery & Psychiatry PG - 1279--1287 VI - 89 IP - 12 4099 - http://jnnp.bmj.com/content/89/12/1279.short 4100 - http://jnnp.bmj.com/content/89/12/1279.full SO - J Neurol Neurosurg Psychiatry2018 Dec 01; 89 AB - 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.