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ObjectiveTo determine whether established heart rate parameters of exercise, related to cardiac autonomic function, are associated with incident Parkinson's disease, independent of both clinical and autonomic prodromal features.MethodsA study of UK Biobank participants who performed a standardized bicycle exercise test (2009-2013), followed until November 2022, and analyzed in January 2024, was carried out. Heart rate increase from rest to exercise, and heart rate decrease from peak exercise to recovery were associated with incident Parkinson's disease. Multivariable adjustment was performed both for clinical characteristics and for prodromal non-cardiac autonomic features.ResultsA total of 69,288 eligible participants (men 48%, mean age 56.8 years [SD 8.2 years]) were followed for 12.5 years: among the 319 (0.5%) who developed Parkinson's disease, recognized prodromal markers (constipation, bladder dysfunction) were more common at baseline. The median lag time to diagnosis was 9.3 years (interquartile range 4.4). Both heart rate increase (37.5 [SD 11.5] vs 40.8 [SD 12.4] b.p.m., p InterpretationCollectively, this suggests that cardiac autonomic involvement precedes clinically manifest Parkinson's disease, and that heart rate recovery might serve as a quantitative prodromal marker. ANN NEUROL 2025;98:1004-1013.
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