Symptom-based indicators of autonomic dysfunction and their bidirectional associations with Parkinson’s disease incidence and adverse outcomes

Abstract

Background Symptom-based indicators suggestive of autonomic dysfunction are common but under-recognized in Parkinson’s disease (PD), with potential implications as a biomarker of aging for early detection and prognosis. We aimed to examine the associations between autonomic dysfunction and PD in a large, population-based cohort. Methods We analysed 374,657 UK Biobank participants free of PD at baseline. Autonomic symptoms—including orthostatic hypotension, constipation, urinary and sexual dysfunction, hyperhidrosis, and other autonomic disorders—was identified via hospital records. Incident PD and subsequent outcomes, including dementia and all-cause mortality, were tracked through June 2023. Cox models estimated hazard ratios for PD and adverse outcomes, and conditional logistic regression assessed the temporal trajectory of autonomic dysfunction relative to PD diagnosis. Results Over a median 14.1-year follow-up, 2,568 participants developed PD. Orthostatic hypotension (HR, 2.91; 95% CI, 1.39 to 6.13), constipation (HR, 1.63; 95% CI, 1.19 to 2.24), urinary dysfunction (HR, 1.45; 95% CI, 1.04 to 2.02), and sexual dysfunction (HR, 3.56; 95% CI, 1.60 to 7.95) independently predicted PD risk. Pre- and post-diagnostic autonomic dysfunction were associated with higher risk of PD dementia and mortality. Autonomic dysfunction was detectable over 10 years before PD diagnosis (OR, 4.46; 95% CI, 3.76 to 5.29), with the strongest association observed within 5 years after PD onset (OR, 8.59; 95% CI, 7.58 to 9.74). Conclusions Symptom-based indicators suggestive of autonomic dysfunction serve as early clinical signals and robust prognostic markers in PD, highlighting their potential utility for early risk stratification and long-term patient management in large population-based settings.