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

BackgroundParkinsons 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. ObjectiveDelineate the current landscape of PD progression at tertiary subspecialty care and research centers. MethodUsing 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. ResultsSubjects (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. ConclusionsTwenty-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.