Trajectories of neurodegeneration in body- and brain-first subtypes of Lewy body disease. In body-first patients (top panel) the sympathetic innervation of the heart starts to degenerate 15-20 years before diagnosis. Prodromal patients with isolated RBD (iRBD) nearly all have severe cardiac denervation (invisble heart), but a normal or near-normal dopamine scan of the brain. When diagnosed with PD, these patients typically have a dopamine scan with rather symmetric loss in the putamen and an invisible heart. In brain-first patients (bottom panel), the dopamine system starts to degenerate early. At the time of PD diagosis, these patients often shown quite asymmetric dopamine loss in the putamen, but most patients still have a normal or near-normal heart scan. A few years later, brain-first patients will start to show loss of the cardiac sympathetic innervation.