Frontiers in Aging Neuroscience 01 frontiersin.org Multifactorial assessment of Parkinson’s disease course and outcomes using trajectory modeling in a multiethnic, multisite cohort – extension of the LONG-PD study Bruce A. Chase 1 , Rejko Krueger 2,3,4,5 , Lukas Pavelka 3,4,5 , Sun Ju Chung 6 , Jan Aasly 7,8† , Efthimios Dardiotis 9 , Ashvini P. Premkumar 10 , Bernadette Schoneburg 10 , Ninith Kartha 10 , Navamon Aunaetitrakul 10 , Roberta Frigerio 10 , Demetrius Maraganore 11 and Katerina Markopoulou 10,12 * 1 Health Information Technology, NorthShore University HealthSystem, Evanston, IL, United States, 2 Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg, 3 Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg, 4 Centre Hospitalier de Luxembourg (CLG), Luxembourg, Luxembourg, 5 Parkinson’s Research Clinic, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg, 6 Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 7 Department of Neurology, St. Olav’s Hospital, Trondheim, Norway, 8 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway, 9 Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece, 10 Department of Neurology, NorthShore University HealthSystem, Evanston, IL, United States, 11 Department of Neurology, Tulane University, New Orleans, LA, United States, 12 Department of Neurology, University of Chicago Pritzker School of Medicine, Chicago, IL, United States Background: The severity, progression, and outcomes of motor and non-motor symptoms in Parkinson’s disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors of disease severity and progression. Methods: PD patients (N =  871) were enrolled at five sites. Enrollment occurred within 5 years of initial motor symptom onset. Disease progression was assessed annually for 2-to-10  years after onset. Group-based trajectory modeling was used to identify groups differing in disease progression. Models were developed for UPDRS-III scores, UPDRS-III tremor and bradykinesia-rigidity subscores, Hoehn & Yahr (H&Y) stage, Mini-Mental Status Exam (MMSE) scores, and UPDRS- III, H&Y and MMSE scores considered together. Predictors of trajectory-group membership were modeled simultaneously with the trajectories. Kaplan–Meier survival analysis evaluated survival free of PD outcomes. Results: The best fitting models identified three groups. One showed a relatively benign, slowly progressing trajectory (Group 1), a second showed a moderate, intermediately progressing trajectory (Group 2), and a third showed a more severe, rapidly progressing trajectory (Group 3). Stable trajectory-group membership occurred relatively early in the disease course, 5 years after initial motor symptom. Predictors of intermediate and more severe trajectory-group membership varied across the single variable models and the multivariable model jointly considering UPDRS-III, H&Y and MMSE scores. In the multivariable model, membership in Group 2 (28.4% of patients), relative to Group 1 (50.5%), was associated with male sex, younger age-at-onset, fewer education-years, pesticide exposure, OPEN ACCESS EDITED BY Allison Schaser, Purdue University, United States REVIEWED BY Jacopo Pasquini, University of Pisa, Italy Jesse Hoffmeister, University of Minnesota Twin Cities, United States Chien Tai Hong, Taipei Medical University, Taiwan *CORRESPONDENCE Katerina Markopoulou amarkopoulou@northshore.org † Deceased RECEIVED 15 June 2023 ACCEPTED 28 August 2023 PUBLISHED 26 September 2023 CITATION Chase BA, Krueger R, Pavelka L, Chung SJ, Aasly J, Dardiotis E, Premkumar AP, Schoneburg B, Kartha N, Aunaetitrakul N, Frigerio R, Maraganore D and Markopoulou K (2023) Multifactorial assessment of Parkinson’s disease course and outcomes using trajectory modeling in a multiethnic, multisite cohort – extension of the LONG-PD study. Front. Aging Neurosci. 15:1240971. doi: 10.3389/fnagi.2023.1240971 COPYRIGHT © 2023 Chase, Krueger, Pavelka, Chung, Aasly, Dardiotis, Premkumar, Schoneburg, Kartha, Aunaetitrakul, Frigerio, Maraganore and Markopoulou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Original Research PUBLISHED 26 September 2023 DOI 10.3389/fnagi.2023.1240971