Cardiac autonomic function during exercise and incident Parkinson's disease

ObjectiveTo determine whether established parameters of cardiac autonomic function are associated with incident Parkinsons disease, independent of clinical characteristics, and established autonomic prodromal features. Methods Population-based cohortstudy of UK Biobank participants who performed a standardized bicycle exercise test (2009-2013), followed until November 2022, and analyzed in January 2024. Heart rate increase from rest to exercise, and the decrease in heart rate from peak exercise to recovery were extracted and associated with incident Parkinsons disease. Associations were adjusted using multivariable models consisting of clinical characteristics only and combined with prodromal autonomic features. Results69,288 eligible participants (male 48%, mean age 56.8 [SD 8.2]) were followed for 12.5 years (median; IQR 0.3): 319 (0.5%) developed Parkinsons disease. Median lag time to diagnosis was 9.3 years (IQR 4.4). Both heart rate increase (37.5 [SD 11.5] vs 40.8 [SD 12.4] beats/min, p < 0.001) and recovery (23.4 [SD 8.8] vs. 27.8 [SD 10.3] beats/min, p < 0.001) were significantly lower in incident cases compared to controls. After adjusting for prodromal clinical and autonomic features, heart rate recovery was independently associated with incident Parkinsons disease, while heart rate increase was not. Specifically, a blunted heart rate lowering during recovery was associated with a 30% higher risk of incident Parkinsons disease (HR: 1.3; 95% CI 1.1-1.4; p < 0.001 per 10 beats less recovery) InterpretationThese findings suggest that cardiac autonomic dysfunction precedes clinically manifest Parkinsons disease, and that heart rate recovery might serve as a quantitative prodromal marker.