Striatal Dopaminergic Asymmetry as a marker of Brain-First and Body-First Subtypes in de novo Parkinson's Disease

Recently, the -Synuclein Origin and Connectome (SOC) model of Parkinson's disease (PD) has been proposed, which predicts a more malignant clinical subtype and symmetrical neurodegeneration in body-first compared to brain-first PD. Here, motor symptoms (MDS-UPDRS III), non-motor symptoms (NMSQ) and T1 MRI data of an incident de novo PD cohort, were compared between PD subjects with levels of putaminal dopaminergic asymmetry in the lowest tertile (PD-sym, n=41) and highest tertile (PD-asym, n=41), as measured by FDOPA-PET. PD-sym was associated with a higher burden of motor symptoms and non-motor symptoms with a probable neurological substrate caudally from the substantia nigra. Though overall brain volume was lower in PD-sym, no differences in the volumes and asymmetricity of specific brain regions could be found between PD-sym and PD-asym after adjusting for multiple testing. The more malignant clinical picture suggests an overrepresentation of body-first PD subjects in PD-sym according to the SOC-model. Also, lower overall brain volumes were found in PD-sym. However, structural MRI data might not be sufficient to assess regional differential degeneration between PD-sym and PD-asym in de novo PD. Additional imaging modalities and longitudinal follow-up could be required to support or reject the SOC-model.