Objective: To objectively assess cardiovascular autonomic function in patients with Parkinson’s disease (PD) carrying pathogenic variants of beta-glucocerebrosidase gene (GBA-PD) and compare to non-mutated PD (NM-PD).

Background: Studies based on clinical scales suggest an association between dysautonomia and GBA-PD [1,2]. So far, a comprehensive evaluation of the cardiovascular autonomic system in GBA-PD patients with standard clinical methodology [3] is lacking.

Method: 33 GBA-PD patients carrying pathogenic variants matched with 34 NM-PD patients without variants in PD-related genes underwent a battery of three tests: Head-up tilt test, Deep breathing, and Valsalva maneuver. The occurrence and severity of dysautonomia were graded using the Composite Autonomic Severity Score cardiovascular section (cv-CASS)[4]. Patients with a cv-CASS score ≥1 were diagnosed with cardiovascular dysautonomia. Autonomic test results were compared with Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT)[5]. Depending on variant severity, patients were divided into five subgroups, to assess whether severe variants bear a higher risk of dysautonomia. Logistical regression analysis was performed to assess which factors influence on cv-CASS.

Results: Age at disease onset was lower in the GBA-PD group (table 1). Otherwise, the two groups were comparable at baseline.

The GBA-PD patients showed a higher supine heart rate (HR), suggesting an impaired sympathovagal balance at rest, as previously reported [6], while they had a higher orthostatic HR, suggesting a preserved sympathetic response to standing (table 2). The GBA-PD group scored worse in all individual autonomic tests, although statistical significance was reached only for CASS parasympathetic sub-score. The number of patients with a CASS score ≥ 1 was similar between groups, as the sympathetic sub-score, which did not differ between groups, had a higher weight. Total and cardiovascular SCOPA-AUT score confirmed these results .               

Variant severity did not correlate with cv-CASS (table 3).

In the GBA-PD group, the total cv-CASS and CASS sympathetic scores were influenced by age at onset of PD (table 4).

Conclusion: Cardiovascular dysautonomia is more frequent in GBA-PD and may affect prevalently and at an earlier stage the parasympathetic system, suggesting an ascending spreading of pathology via vagus nerve [7] as in body-first PD subtype [8].

References: 1. Cilia R, et al. Survival and dementia in GBA-associated Parkinson’s disease: The mutation matters. Ann Neurol. 2016 Nov;80(5):662-673
2. Petrucci S, et al. GBA-Related Parkinson’s Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort. Mov Disord. 2020 Nov;35(11):2106-2111
3. Cheshire, W. P. et al. W. Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American
Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol. 2021 Feb;132(2):666-682
4. Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748-52
5. Rodriguez-Blazquez C et al. Independent validation of the scales for outcomes in Parkinson’s disease-autonomic (SCOPA-AUT). Eur J Neurol. 2010 Feb;17(2):194-201.
6. Carandina A, et al. Dysautonomia in Parkinson’s Disease: Impact of Glucocerebrosidase Gene Mutations on Cardiovascular Autonomic Control. Front Neurosci. 2022 Mar 15;16: 842498
7. Kim MS, et al. Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson’s disease patients with GBA mutations: evidence of the body-first type? Eur J Neurol. 2023 Feb;30(2):344-352
8. Borghammer P, et al. Brain-First versus Gut-First Parkinson’s Disease: A Hypothesis. J Parkinsons Dis. 2019;9(s2):S281-S295

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cardiovascular-autonomic-function-in-gba-associated-parkinsons-disease-a-cross-sectional-study/