Cardiac autonomic function during exercise and incident Parkinson’s disease

Objective To determine whether established parameters of cardiac autonomic function are associated with incident Parkinson’s disease, independent of clinical characteristics, and established autonomic prodromal features. Methods Population-based cohort study 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 Parkinson’s disease. Associations were adjusted using multivariable models consisting of clinical characteristics only and combined with prodromal autonomic features. Results 69,288 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 Parkinson’s 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 Parkinson’s disease, while heart rate increase was not. Specifically, a blunted heart rate lowering during recovery was associated with a 30% higher risk of incident Parkinson’s disease (HR: 1.3; 95% CI 1.1-1.4; p < 0.001 per 10 beats less recovery) Interpretation These findings suggest that cardiac autonomic dysfunction precedes clinically manifest Parkinson’s disease, and that heart rate recovery might serve as a quantitative prodromal marker.