Early Autonomic Burden in Prodromal Parkinson's Disease Predicts Cognitive Impairment

Background: Autonomic dysfunction is a known contributor to cognitive impairment in Parkinson's disease (PD), but its impact during prodromal stage is unknown. Objective: The aim was to determine whether early autonomic burden predicts incident cognitive impairment in prodromal PD. Methods: We analyzed data from Parkinson's Progression Markers Initiative participants. Autonomic dysfunction was defined as Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction score ≥13, documented prior to phenoconversion. Cox regression assessed the predictors of cognitive impairment, and mixed-effects analysis of variance compared domain-specific cognitive trajectories. Results: Data on 382 participants were analyzed. Early autonomic dysfunction was significantly associated with increased risk of mild cognitive impairment or dementia (P < 0.001), especially in semantic fluency and letter-number sequencing. Cardiovascular autonomic burden, specifically, was a strong independent predictor (HR = 5.21, P = 0.01). Conclusions: Autonomic dysfunction in prodromal PD is a risk factor for cognitive decline, providing opportunity for early risk stratification and intervention.