Objective: To investigate the relationships between autonomic dysfunction, clinical severity, and striatal dopaminergic deficits in de novo Parkinson’s disease (PD), and to determine whether these relationships differ by probable REM-sleep behavior disorder (pRBD) status.

Background: Comprehensive integration of autonomic, motor, and cognitive domains in PD with RBD remains limited. Evidence on the multimodal association between subjective clinical assessments and objective testing in de novo PD has not been fully established.

Method: This cross-sectional study enrolled 75 de novo PD patients (without pRBD: n=22; with pRBD: n=53). Autonomic symptoms, clinical disease severity, and global cognition were assessed using validated scales (autonomic questionnaire, MDS-UPDRS, MMSE, and MoCA). pRBD was identified via a validated screening questionnaire. Objective autonomic function was evaluated through a battery of cardiovagal, adrenergic, and sudomotor tests, and cardiac MIBG scintigraphy. Striatal dopaminergic integrity was assessed by dopamine transporter (DAT) imaging. Partial Spearman correlations, adjusted for confounders, were performed in the overall cohort and stratified by pRBD status.

Results: Greater autonomic symptom burden and objective autonomic dysfunction correlated with higher MDS-UPDRS scores and reduced striatal DAT uptake. Cardiovagal indices showed the most consistent associations with clinical severity and DAT availability. Stratification by pRBD revealed distinct autonomic-clinical and autonomic-dopaminergic coupling patterns: in patients without pRBD, vagal dysfunction was strongly correlated with MDS-UPDRS scores and striatal DAT loss, while subjective autonomic symptom burden and adrenergic measures were non-significant. In patients with pRBD, sympathetic dysfunction and overall autonomic symptom burden were more closely linked to higher MDS-UPDRS scores, whereas cardiovagal measures showed weaker associations with DAT uptake than those observed in patients without pRBD.

Conclusion: Autonomic coupling in de novo PD differs significantly by pRBD status. Vagal dysfunction emerges as a primary correlate of dopaminergic loss in patients without pRBD, whereas sympathetic dysfunction and symptom burden are more characteristic of PD with pRBD. These findings establish pRBD as a key modifier of autonomic coupling, identifying distinct autonomic phenotypes in early Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/autonomic-coupling-patterns-differ-by-rem-sleep-behavior-disorder-status-in-de-novo-parkinsons-disease/