Prange S, et al. - In this retrospective cohort study, researchers determined the time course of hazard for motor and nonmotor milestones of Parkinson disease (PD) in the long term and examined whether risk scales nonlinearly with time is instrumental in identifying changes in pathological processes and assessing disease-modifying therapies in PD. PD outpatients at the Lyon University Movement Disorders Center were assessed for 7 clinical milestones, comprising 4 domains of PD progression: motor (motor fluctuations, dyskinesias); axial (postural instability and falls, freezing of gait); neuropsychiatric (impulse control disorders, hallucinations); and cognitive (dementia) complications. In total, 1,232 patients with PD had 1,527 complications related to the disease in up to 12 years of follow-up. For each complication, hazard rates increased dramatically from diagnosis and were highest for motor fluctuations and lowest for dementia up to 6 years after diagnosis in patients 65 years of age during diagnosis. In nonlinear patterns and their interaction, the time course of motor and nonmotor milestones in PD is determined by disease duration and age at diagnosis. This shows disease- and age-specific thresholds across the multiple neurodegenerative processes accumulate in PD at different paces.