Age-Linked Sympathetic Denervation Worsens PD Non-Motor Symptoms

Summary: Researchers found that Parkinson’s disease (PD) patients with sympathetic denervation in major salivary glands and the heart exhibit more severe non-motor symptoms as they age.

This research highlights the importance of age in PD progression and could enhance the understanding of the disease’s pathophysiology.

Key Fact:

  • Non-Motor Symptoms: Older PD patients with sympathetic denervation show severe olfactory dysfunction, REM sleep behavior disorder, and autonomic nervous system dysfunction.
  • MIBG Scintigraphy: The study used a quantitative method to analyze MIBG uptake, showing a correlation between denervation and symptom severity.
  • Age Factor: Age significantly impacts the progression of non-motor symptoms in PD, independent of cognitive function and illness duration.

Source: Toho University

Dr. Junya Ebina and Professor Osamu Kano from the Department of Neurology, Toho University Faculty of Medicine, along with Professor Sunao Mizumura from the Department of Radiology, have reported that patients with Parkinson’s disease (PD) exhibiting sympathetic denervation in the major salivary glands and the heart tend to have more advanced non-motor symptoms as they age, suggesting that age plays an important role in disease progression.

This research outcome could potentially contribute to a better understanding of the pathophysiological progression of PD.

This shows an older person.
This study may aid in understanding the pathophysiological progression of PD and may be used for future staging of individual patients. Credit: Neuroscience News

This study was made available online on February 12, 2024 and was published in Article 122932, Volume 458 of the Journal of the Neurological Sciences, on 15 March 2024.

Key Points:

  • PD patients with sympathetic denervation in the major salivary glands and heart , as indicated by MIBG scintigraphy (Note 1), are older and have more severe non-motor symptoms, such as olfactory dysfunction, REM sleep behavior disorder, and autonomic nervous system dysfunction according to questionnaire scores, compared to groups with single sympathetic denervation or non-sympathetic denervation (Table and Figure ). However, cognitive function, duration of illness, and MDS-UPDRS motor symptom scores were comparable between the groups.
  • In this study, a quantitative semi-automatic method developed by the research group last year was used to analyze MIBG uptake in the major salivary glands and heart. This comparative study of clinical symptoms focusing on peripheral organs in patients with PD, as highlighted in Ebina J, et al. J Neurol 2023, may provide a new perspective on disease progression.
  • This study may contribute to understanding the pathophysiological progression of PD, leading to a more accurate staging of PD and enabling tailored medical care according to individual patient conditions. The research group is also examining the utility of novel adjunct diagnostic methods.

Presentation Overview:

PD is a progressive neurodegenerative disorder characterized by abnormal aggregates of α-synuclein known as Lewy bodies. Lewy bodies are not only found in the central nervous system but also in peripheral organs.

In PD, cardiac sympathetic denervation detected by 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is associated with the presence of Lewy bodies. Conversely, although Lewy bodies are frequently found in the digestive tract, including in the major salivary glands, the process of pathophysiological progression in peripheral organs is unclear.

A research group previously reported sympathetic denervation in the submandibular and parotid glands of patients with PD. Therefore, in this study, they hypothesized and verified whether patients with PD and sympathetic nerve dysfunction in the heart and major salivary glands have more advanced clinical symptoms.


Patients with PD with sympathetic denervation in both major salivary glands and heart areas (dual-SD group) were found to be older, have more severe olfactory dysfunction, and a higher likelihood of having REM sleep behavior disorder and severe autonomic nerve dysfunction compared to the single-SD group or non-SD group.

However, the duration of illness and cognitive function were similar among the groups. Logistic regression analysis with age, sex, and duration of illness as variables showed that age was an important factor affecting clinical evaluation items in the progression of the disease.

In conclusion, patients with PD and decreased MIBG uptake in both the major salivary glands and heart areas exhibited a progression of symptoms centered around non-motor symptoms, suggesting that autonomic nerve dysfunction may progress independently of nigrostriatal dopaminergic degeneration.

Furthermore, the potential contribution of age to the pathophysiological progression of PD was suggested. This study may aid in understanding the pathophysiological progression of PD and may be used for future staging of individual patients.

About this Parkinson’s disease research news

Author: Akira Muto
Source: Toho University
Contact: Akira Muto – Toho University
Image: The image is credited to Neuroscience News

Original Research: Open access.
Clinical characteristics of patients with Parkinson’s disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart” by Junya Ebina et al. Journal of the Neurological Sciences


Abstract

Clinical characteristics of patients with Parkinson’s disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart

Highlights

  • MIBG uptake in the major salivary glands is reduced in Parkinson’s disease.
  • Parkinson’s disease with dual reduced MIBG uptake shows advanced non-motor symptoms.
  • Autonomic dysfunction might progress independently from dopaminergic degeneration.
  • Aging is a crucial factor in Parkinson’ disease.

Abstract

Background

Parkinson’s disease (PD) shows cardiac sympathetic denervation (SD) in 123I-metaiodobezylguanidine (MIBG) scintigraphy. Recently, SD in the major salivary glands (MSG-SD) was introduced as a possible radiological feature of PD.

Objective

To identify the clinical characteristics of patients with PD with reduced MSG and cardiac MIBG uptake (dual-SD) compared with those with reduced MSG or cardiac MIBG uptake only (single-SD).

Methods

We recruited 90 patients with PD and 30 controls and evaluated their non-motor (e.g., hyposmia, autonomic dysfunction) and motor (e.g., Movement Disorder Society-Unified Parkinson’s Disease Rating Scale) features. We also assessed MIBG uptake in the MSG and heart using a quantitative semi-automatic method, and compared MIBG uptakes between PD and controls. We set cut-off values for optimal sensitivity and specificity, and compared the clinical characteristics of patients with PD between dual- and single-SD groups.

Results

MSG and cardiac MIBG uptakes were significantly reduced in PD. Sixty-one patients had dual-SD, 25 had single-SD, and four had non-SD. In patients with PD with normal cardiac SD, 76.5% (13/17) of whom showed abnormalities only in MSG-SD. When clinical characteristics were compared between the dual-SD and single−/non-SD groups, patients in the dual-SD group were older and had more severe hyposmia and autonomic dysfunction, except motor features. Multiple logistic regression analysis identified age as an important confounder.

Conclusions

Patients with PD with dual-SD have more severe non-motor features than other patients. Autonomic dysfunction might progress independently from dopaminergic degeneration. Furthermore, our findings indicate that aging is a crucial factor in PD progression.

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