Exploring cardiac autonomic dysfunction in synucleinopathies with parkinsonism through awake-sleep stages: a possible connection to cardiovascular death.

Introduction: Alpha-synucleinopathies (ASs), including Parkinson's disease, multiple system atrophy and dementia with Lewy bodies, are characterised by autonomic dysfunction that may predispose to cardiovascular events and sudden death. Heart rate variability (HRV) is a non-invasive marker of autonomic regulation, yet its modulation across sleep stages in ASs remains unclear. Methods: We retrospectively analysed 25 patients with ASs and 35 age-matched controls who underwent overnight polysomnography between 2020 and 2023. 5 min ECG segments from wakefulness, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were used to compute time- and frequency-domain HRV indices. Statistical comparisons and multivariate models were adjusted for sex and REM sleep behaviour disorder. Results: HRV indices, particularly percentage of successive RR intervals that differ by more than 50 milliseconds (pNN50) and root mean square of successive differences, were significantly reduced in ASs compared with controls. The most pronounced difference occurred during NREM sleep (pNN50, p=0.008), where controls exhibited normal parasympathetic elevation that was absent in ASs. Conclusion: Patients with ASs demonstrate blunted nocturnal parasympathetic activity, most evident during NREM sleep. Sleep-stage-specific HRV analysis provides sensitive insights into cardiac autonomic dysfunction and may serve as a potential biomarker of disease severity and cardiovascular risk in synucleinopathies.