The thin line represents the continuous degeneration of the dopaminergic neurons of the substantia nigra. When dopaminergic neuronal loss reaches >50%, cardinal motor symptoms appear (thick line) and PD becomes fully symptomatic (gray background). Motor symptoms worsen over time but respond to dopamine replenishment therapy.
During the premotor phase (white background) non-motor symptoms (dotted line) may already be present. Non-motor symptoms burden also increases with time but contrary to motor symptoms do not respond to treatment and constitute most of the disability in advanced PD.