A predictive model of neurodegeneration in idiopathic REM-sleep behavior disorder

ObjectiveTo investigate whether Parkinson's disease (PD) and dementia are competing risks in subjects with idiopathic rapid-eye-movement sleep behavior disorder (RBD).MethodsThe number of incidental PD cases observed in 11 longitudinal RBD studies was compared with the corresponding expected number as estimated by a simple mathematical model based on population parameters for PD age-of-onset.ResultsThe expected number of incidental PD cases exceeded observed PD cases (p-value < 0.001) but was in agreement with the sum of observed PD cases and observed mild cognitive impairment/dementia cases (p-value = 0.34). Sensitivity analyses confirmed the results.ConclusionIn the RBD population, PD and dementia cases are competing risks, suggesting that alpha-synuclein pathology occurs simultaneously in substantia nigra and neocortex. This observation has implications for the design and analysis of trials of neuroprotection.