Exploring the relation between REM sleep behavior disorder onset and striatal dopaminergic dysfunction in Parkinson’s Disease

Background: The α-Synuclein Origin and Connectome (SOC) model recently proposed two different Parkinson’s Disease (PD) phenotypes clinically based on the relationship between REM sleep behavior disorder (RBD) and motor symptoms’ onset: a “body first” phenotype and a “brain first” phenotype in which RBD precedes or may follow the motor onset, respectively. A higher burden of non-motor symptoms as well as a more symmetrical clinical presentation have also been predicted in the body-first phenotype. This point has been poorly assessed through semi-quantitative striatal dopaminergic functional imaging to date. Objectives: To explore the relation between RBD onset and striatal dysfunction in PD. Methods: PD patients were retrospectively enrolled and clinical follow-up data were gathered. Presence and onset of probable RBD were evaluated classifying patients into PD-RBDpre (onset before motor symptoms), PD-RBDpost (onset after motor symptoms) and PD-RBD-. Semi-quantitative 123I-FP-CIT-DAT-SPECT imaging was performed at baseline. Mean putamen and caudate-specific binding ratios (SBR) and asymmetry index (AI) were computed. Results: Fifty-six PD patients were enrolled (10 PD-RBDpre, 19 PD-RBDpost and 27 PD-RBD-). A more symmetrical motor impairment, higher mild cognitive impairment (MCI) prevalence, lower caudate SBR and lower putamen AI were found in PD-RBDpre. A negative trend in MCI prevalence as well as a positive trend in both caudate SBR and putamen AI were found across PD-RBDpre, PD-RBDpost and PD-RBD-. Conclusions: Different patterns of striatal dopaminergic dysfunction and cognitive impairment based on RBD onset were unraveled, supporting the SOC model’s predictions.