Parkinson Disease–Related Brain Metabolic Patterns and Neurodegeneration in Isolated REM Sleep Behavior Disorder

ABSTRACTObjective:To elucidate the role of Parkinson’s disease (PD)-related brain metabolic patterns as a biomarker in isolated rapid-eye-movement sleep behavior disorder (iRBD) for future disease conversion.Method:This is a prospective cohort study consisting of 30 iRBD patients, 25 de novo PD patients with a premorbid history of RBD, 21 long-standing PD patients on stable treatment and 24 healthy controls. iRBD group was longitudinally followed up. All participants underwent 18F-Fluorodeoxyglucose (FDG) PET and were evaluated with olfaction, cognition, and the Movement disorders society-Unified PD Rating Scale (MDS-UPDRS) at baseline. From FDG-PET scans, we derived metabolic patterns from the long-standing PD group (PD-RP) and de novo PD group with RBD (dnPDRBD-RP). Subsequently, we calculated the PD-RP and dnPDRBD-RP scores in iRBD patients. We validated the metabolic patterns in each PD group and separate iRBD cohort (n=14).Result:The two patterns significantly correlated with each other and were spatially overlapping yet distinct. The MDS-UPDRS motor scores significantly correlated with PD-RP (p = 0.013) but not with dnPDRBD-RP (p = 0.076). In contrast, dnPDRBD-RP correlated with olfaction in butanol threshold test (p = 0.018) in iRBD subjects, but PD-RP did not (p = 0.21). High dnPDRBD-RP in iRBD patients predicted future phenoconversion with all cut-off ranges from 1.5 to 3 standard deviations of the control value, whereas predictability of PD-RP was only significant in a partial range of cut-off.Conclusion:The dnPDRBD-RP is an efficient neuroimaging biomarker that reflects prodromal features of PD and predicts phenoconversion in iRBD that can be applied individually.Classification of Evidence:This study provides Class IV evidence that a de novo Parkinson's disease pattern on FDG-PET predict future conversion to neurodegenerative disease in patients with isolated rapid-eye-movement sleep behavior disorder (iRBD).