Brain Glucose Metabolism Heterogeneity in Idiopathic REM Sleep Behavior Disorder and in Parkinson's Disease

Background/Objective: Idiopathic REM sleep behavior disorder (iRBD) often precedes Parkinson's disease (PD) and other alpha-synucleinopathies. The aim of the study is to investigate brain glucose metabolism of patients with RBD and PD by means of a multidimensional scaling approach, using F-18-FDG-PET as a biomarker of synaptic function. Methods: Thirty-six iRBD patients (64.1 +/- 6.5 y, 32 M), 72 PD patients, and 79 controls (65.6 +/- 9.4 y, 53 M) underwent brain F-18-FDG-PET. PD patients were divided according to the absence (PD, 32 subjects; 68.4 +/- 8.5 y, 15 M) or presence (PDRBD, 40 subjects; 71.8 +/- 6.6 y, 29 M) of RBD. F-18-FDG-PET scans were used to independently discriminate subjects belonging to four categories: controls (RBD no, PD no), iRBD (RBD yes, PD no), PD (RBD no, PD yes) and PDRBD (RBD yes, PD yes). Results: The discriminant analysis was moderately accurate in identifying the correct category. This is because the model mostly confounds iRBD and PD, thus the intermediate classes. Indeed, iRBD, PD and PDRBD were progressively located at increasing distance from controls and are ordered along a single dimension (principal coordinate analysis) indicating the presence of a single flux of variation encompassing both RBD and PD conditions. Conclusion: Data-driven approach to brain F-18-FDG-PET showed only moderate discrimination between iRBD and PD patients, highlighting brain glucose metabolism heterogeneity among such patients. iRBD should be considered as a marker of an ongoing condition that may be picked-up in different stages across patients and thus express different brain imaging features and likely different clinical trajectories.