Which Autonomic Symptoms Can Predict Cognitive Progression Milestones in Parkinson's Disease? An Item-Level SCOPA-AUT Analysis

Abstract Purpose Autonomic dysfunction and cognitive decline are common in Parkinson's disease and may share pathophysiological mechanisms. We examined whether specific baseline autonomic symptoms predict the development of cognitive progression milestones. Methods We analyzed 960 Parkinson's disease patients from the Parkinson's Progression Markers Initiative who had baseline Scales for Outcomes in Parkinson's Disease–Autonomic assessment, baseline Montreal Cognitive Assessment score ≥ 21, and no baseline dementia. The primary outcome was reaching any cognitive milestone. Cox proportional hazards models were used for each autonomic item, adjusted for age, sex, education, baseline cognition, and motor severity, with false discovery rate correction. Results Over a median follow-up of 4.0 years, 227 patients (23.6%) reached a cognitive milestone. Eight items independently predicted cognitive milestones after false discovery rate correction: swallowing/choking, drooling, straining, urgency, frequency, lightheadedness on standing, lightheadedness while walking, and cold intolerance. Four of six autonomic domains were significant predictors: gastrointestinal, urinary, cardiovascular, and thermoregulatory. Kaplan–Meier analysis showed a dose–response relationship across autonomic symptom burden tertiles (log-rank p < 0.001). Results were robust across sensitivity analyses including 4-year minimum follow-up and individual milestone definitions. Conclusions Multiple baseline autonomic symptoms across gastrointestinal, urinary, cardiovascular, and thermoregulatory domains independently predict cognitive milestones in Parkinson's disease. These findings support shared pathophysiological mechanisms between autonomic dysfunction and cognitive decline and suggest that autonomic assessment may contribute to prognostic stratification.