Progression trajectories from prodromal to overt synucleinopathies: a longitudinal, multicentric brain [18F]FDG-PET study

The phenoconversion trajectory from idiopathic/isolated Rapid eye movement (REM) sleep behavior disorder (iRBD) towards either Parkinson’s Disease (PD) or Dementia with Lewy Bodies (DLB) is currently uncertain. We investigated the capability of baseline brain [¹⁸F]FDG-PET in differentiating between iRBD patients eventually phenoconverting to PD or DLB, by deriving the denovoPDRBD-related pattern (denovoPDRBD-RP) from 32 de novo PD patients; and the denovoDLBRBD-RP from 30 de novo DLB patients, both with evidence of RBD at diagnosis. To explore [¹⁸F]FDG-PET phenoconversion trajectories prediction power, we applied these two patterns on a group of 115 iRBD patients followed longitudinally. At follow-up (25.6 ± 17.2 months), 42 iRBD patients progressed through overt alpha-synucleinopathy (21 iRBD-PD and 21 iRBD-DLB converters), while 73 patients remained stable at the last follow-up visit (43.2 ± 27.6 months). At survival analysis, both patterns were significantly associated with the phenoconversion trajectories. Brain [¹⁸F]FDG-PET is a promising biomarker to study progression trajectories in the alpha-synucleinopathy continuum.