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The neurodegenerative synucleinopathies, namely Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), have a long prodromal interval: a period during which neurodegenerative signs are evident, but remain below the threshold of clinical parkinsonism or dementia.1 This provides a major window of opportunity to intervene with neuroprotective therapy, perhaps even preventing clinical disease. By far the strongest clinical marker of prodromal synucleinopathy is idiopathic/isolated REM sleep behavior disorder (iRBD). Large multicenter trials have documented that the large majority of patients with iRBD will eventually develop neurodegenerative disease, almost always a synucleinopathy.2 This makes patients with iRBD the ideal candidates for early neuroprotective trials. Considerable effort is being made to define the precise risk of disease phenoconversion, identify markers of increased risk, and delineate potential outcome measures for such trials.
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