Objective: To evaluate cardiovascular autonomic dysfunction across prodromal stages of synucleinopathies (Pure Autonomic Failure-PAF); isolated REM Sleep Behavior Disorder-iRBD) and early stages of Parkinson’s disease (PD), assessing both sympathetic and parasympathetic functions.

Background: Autonomic dysfunction is considered a prodromal marker of synucleinopathies, often manifesting years before the onset of motor symptoms[1]. However, no studies have comprehensively evaluated or compared cardiovascular dysfunction profiles in PAF, iRBD, and earlyPD.

Method: Cardiovascular autonomic functions were assessed in PAF patients from the “IAF-BO cohort”[2]; iRBD patients from the “iRBD cohort”[3] and earlyPD patients from the “BoProPark study”[4]. Cardiovascular reflex tests (CRTs) were performed at the time of first diagnosis and included the head-up tilt test (HUTT), Valsalva manoeuvre (VM), deep breathing (DB), cold face (CF) and handgrip (HG) under continuous blood pressure (BP) and heart rate (HR) monitoring. Group comparisons were made using Kruskal-Wallis and chi-square tests.

Results: The study included 72 PAF patients (age: 64.00[14.00] years, disease duration: 6.00[5.50] years); 67 iRBD (age: 68.0[8.00] years, disease duration:4,50[6,50] years) and 99 PD (age: 63,50[11.50] years, disease duration: 1,50[1,00]years).

Cardiovascular autonomic dysfunction was detected in 100% of PAF patients, 37% of iRBD patients and 9% of PD patients. PAF patients showed a significantly higher BP drop at HUTT and reduced BP responses during VM (overshoot, SBP IIb-IIa) compared to iRBD and PD [Figure 1]. Additonally, iRBD patients exhibited significantly reduced BP responses at HUTT and VM compared to PD.

PAF patients also presented pathological Valsalva ratio (VR) and inspiration/expiration HR ratio (I/E) compared to both iRBD and PD. Furthermore, iRBD patients showed lower VR and I/E compared to PD. Responses to CF and HG were reduce exclusively in PAF patients.

Conclusion: Cardiovascular autonomic dysfunction is already severe in PAF patients at the first evaluation, affecting both sympathetic and parasympathetic functions. In iRBD patients, early impairment of sympathetic baroreflex function is detectable, with milder involvement observed in PD patients. This study highlights the distinct autonomic profiles of PAF, iRBD, and PD, suggesting that prodromal stages do not fully represent the entire PD population.

Figure 1

References: [1] Heinzel, S. et al. (2019). Update of the MDS research criteria for prodromal Parkinson’s disease. Movement Disorders. https://doi.org/10.1002/mds.27802.
[2] Giannini, G. et al. (2018). The natural history of idiopathic autonomic failure. Neurology. https://doi.org/10.1212/WNL.0000000000006243.
[3] Baldelli, L. et al. (2023). Epigenetic clocks suggest accelerated aging in patients with isolated REM Sleep Behavior Disorder. npj Parkinson’s Disease. https://doi.org/10.1038/s41531-023-00492-2.
[4] Calandra-Buonaura, G. et al.The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark): study design and population. https://doi.org/10.1007/s10072-020-04305-9/Published.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-autonomic-dysfunction-in-prodromal-and-early-stages-of-parkinsons-disease/