[18F] FDG-PET-based Parkinson's Disease-related Metabolic Brain Pattern (PDRP) As A Progression Biomarker: A 4-year Follow-up In A Cohort Of Patients With Idiopathic Rem Sleep Behavior Disorder (iRBD)

Background: iRBD is commonly considered to be a prodromal stage of alpha-synucleinopathies such as Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), or Multiple System Atrophy (MSA). The characteristic brain pathology in PD results in a pattern of abnormal cerebral glucose metabolism known as the PD-related pattern (PDRP). The degree of this pattern expression can be quantified in any [18F]FDG-PET brain scan. Previous reports have shown that this pattern is a useful biomarker of disease progression and of phenoconversion from iRBD to PD. It may also be useful for identifying the approximately 10-20% of iRBD patients who will not convert to a parkinsonian disorder so that they may be excluded from future parkinsonian drug trials targeting the prodromal phase. Methods: In our first study (“REMPET1”), 21 iRBD patients without parkinsonism or dementia, 19 controls, 20 PD patients, and 22 DLB patients underwent static [18F]FDG-PET brain imaging. PDRP expression values were then computed using spatial covariance (SSM/PCA) analysis and z-transformed to control values. In our follow-up study (“REMPET2”), we have begun rescanning the 21 iRBD subjects to follow the progression in their PDRP expressions since their last scans. Results: In our baseline study (published November 2017 in the Movement Disorders Journal), PDRP expression was higher in iRBD patients compared to healthy controls (p=0.048), but lower compared to PD (p=0.001) and DLB patients (p<0.0001). 12/21 iRBD subjects (57%) already had a suprathreshold PDRP expression. In our preliminary follow-up results so far, it appears that PDRP expression has significantly increased in most iRBD subjects rescanned compared to their initial scans from approximately 4 years ago. Additionally, some of the subjects appear to have developed early signs of parkinsonism according to the MDS-UPDRS. Conclusion:Our preliminary findings show that abnormal metabolic expression begins years before clinical manifestation of parkinsonian symptoms in iRBD patients, and that changes in PDRP expression over time may provide a useful metric for predicting phenoconversion to alpha-synucleinopathy diseases.