Striatal (a-)Symmetry Reveals Gender-Specific Autonomic Vulnerabilities in early Parkinson’s Disease

Autonomic symptoms are common in Parkinson’s disease and vary according to patterns of dopaminergic neurodegeneration. Based on the alpha-Synuclein Origin site and Connectome model, which distinguishes “brain-first” and “body-first” Parkinson’s disease phenotypes, this study investigates how striatal denervation asymmetry and gender influence autonomic dysfunction profiles in early-stage, treatment-naive Parkinson’s disease. Using data from the Parkinson's Progression Markers Initiative ( n  = 759), we applied generalized linear mixed models to assess SCOPA-AUT scores across subtypes of striatal denervation (left-predominant, right-predominant, symmetric), while accounting for gender. Patients with symmetric striatal denervation exhibited significantly greater overall autonomic dysfunction, particularly in sexual domains. Gender-specific effects emerged: women showed more pronounced thermoregulatory symptoms, whereas men exhibited more severe urinary and sexual dysfunction, especially in the symmetric group. These findings suggest the potential of integrating striatal denervation asymmetry and gender into Parkinson’s disease subtype characterization, with implications for personalized symptom management and therapeutic strategies from the early stages of the disease.