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.

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image Image Characteristics of proposed body-first and brain-first subtypes of PD. Arrows indicate the direction of spread of α-synuclein pathology. In body-first Parkinson disease (left), the first α-synuclein aggregation occurs in the gut and propagates through the sympathetic nervous system to the sympathetic trunk and heart, and via the vagus nerve to the brainstem. Autonomic dysfunction and REM sleep behaviour disorder (RBD) are prodromal features. In brain-first PD (right), the initial α-synuclein pathology enters via the olfactory bulb (OB) and spreads to the amygdala and nigrostriatal dopamine system. The pathology then descends through the brainstem and RBD and dysautonomia generally develop after the onset of parkinsonism. During the later disease stages, nearly all patients have widespread pathology in these systems and their symptomatology therefore converges.
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