Striatal (a-)symmetry reveals sex-specific autonomic vulnerabilities in early Parkinson’s disease

Autonomic symptoms are common in Parkinson's disease and vary according to patterns of dopaminergic neurodegeneration. The impact of sex and striatal denervation asymmetry are interesting avenues for observing distinct patient phenotypes from the early stages of the disease. This exploratory study investigates how striatal denervation asymmetry and sex influence autonomic dysfunction profiles in early-stage, treatment-naive Parkinson's disease. Using data from the Parkinson's Progression Markers Initiative (<i>n</i> = 759), we applied generalized linear mixed models to assess SCOPA-AUT scores across subtypes of striatal denervation (left-predominant, right-predominant, symmetric), modeling the interaction with sex. Patients with symmetric striatal denervation exhibited significantly greater overall autonomic dysfunction, particularly in sexual domains (<i>p</i> = 0.045). Sex-specific effects emerged: women showed more pronounced thermoregulatory symptoms (<i>p</i> = 0.001), whereas men exhibited more severe urinary and sexual dysfunction, especially in the symmetric group (<i>p</i> < 0.0001). These findings suggest the potential of integrating striatal denervation asymmetry and sex into Parkinson's disease subtype characterization, with implications for personalized symptom management.