CARDIOVASCULAR AUTONOMIC IMPAIRMENT IN GBA PARKINSONIAN PATIENTS

Background: Mutations in the Beta-glucocerebrosidase (GBA) gene are the most common genetic risk factor for Parkinson’s disease (PD). GBA-associated PD (GBA-PD) has been linked to a higher prevalence of non-motor symptoms compared to idiopathic PD (I-PD), raising the question of whether autonomic dysfunction is more frequent or expressed differently in GBA-PD patients. Objectives: This study aimed to investigate cardiovascular autonomic function in GBA-PD patients compared to I-PD patients. The primary objective was to evaluate the prevalence and severity of cardiovascular dysautonomia in GBA-PD patients. Secondary objectives included determining whether dysautonomia primarily affects the sympathetic, parasympathetic, or both systems and performing a genotype-phenotype analysis to explore whether individuals with severe GBA variants are at a greater risk for cardiovascular dysautonomia. Methods: The frequency and severity of autonomic symptoms were measured using the SCOPA-AUT questionnaire. Cardiovascular autonomic reflex testing was conducted in an autonomic laboratory using standard clinical protocols. Spectral analysis of heart rate variability was performed to assess sympatho-vagal balance and vagal tone in both supine and standing positions. Additionally, 123I-MIBG myocardial single-photon emission CT was used to evaluate postganglionic sympathetic nerve terminals. Results: A total of 34 GBA carriers and 33 I-PD patients were included. GBA-PD patients exhibited greater severity of autonomic symptoms compared to the I-PD cohort, as indicated by the SCOPA-AUT questionnaire results. Autonomic testing revealed increased parasympathetic impairment in the GBA-PD group, which was confirmed by spectral analysis showing reduced vagal modulation. The degree of sympathetic cardiac denervation was comparable between the two groups. Conclusions: This study provides evidence of autonomic dysfunction in both GBA-PD and I-PD patients, with a particular emphasis on parasympathetic impairment in the GBA-PD population. Genotype-phenotype analysis did not identify a correlation between the severity of GBA mutations and cardiovascular autonomic dysfunction.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2024

Author dc:creator

• COCCO, ANTONIANGELA

Contributors dc:contributor

• tutor: A. Albanese
• G. Comi ; coordinatore: C. Sforza
• A. Cocco
• COMI, GIACOMO PIETRO
• SFORZA, CHIARELLA

• Parkinson's disease
• , glucocerebrosidase
• dysautonomia
• non-motor symptoms
• Settore MED/26 - Neurologia
• Settore MEDS-12/A - Neurologia

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

http://dx.doi.org/10.13130/cocco-antoniangela_phd2024-06-10
10.13130/cocco-antoniangela_phd2024-06-10

OAI identifier oai:identifier

oai:air.unimi.it:2434/1121075