Clinical progression of Parkinson's disease in the early 21st century: Insights from AMP-PD dataset

Background: Parkinson's disease (PD) therapeutic strategies have evolved since the introduction of levodopa in the 1960s, but there is limited data on their impact on disease progression markers. Objective: Delineate the current landscape of PD progression at tertiary subspecialty care and research centers. Method: Using Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years. Results: Subjects' (3,001 PD cases: 2,838 white, 1,843 males) mean age at diagnosis was 60.2 ±] 10.3 years and disease duration was 9.9 ± 6.0 years at the baseline evaluation. Participants largely reported independence (S&E, 5y: 86.6 ± 12.3; 10y: 78.9 ± 19.3; 15y: 78.5 ± 17.0) and good quality of life (PDQ-39, 5y: 15.5 ± 12.3; 10y: 22.1 ± 15.8; 15y: 24.3 ± 14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ~10-15 years. Younger onset age correlated with slower overall (S&E), motor (MDS-UPDRS-III), and non-motor (UPSIT/MoCA) progression, and females had better overall motor (MDS-UPDRS-II-III) and non-motor (UPSIT) scores than males. Conclusions: Twenty-first century PD patients remain largely independent in the first decade of disease. Female and young age of diagnosis were associated with better clinical outcomes. There are data gaps for non-whites and metrics that gauge non-motor progression for >10 years after diagnosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported in part by the National Institute of Neurological Disorders and Stroke (NS060722, NS082151 and NS112008; XH PI), Penn State College of Medicine Translational Brain Research Center, and Michael J. Fox Foundation for Parkinson's Research (18078; GD PI). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: AMP-PD (https://amp-pd.org/) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript