Biological Determinants and Neural Compensatory Mechanisms of Oropharyngeal Dysphagia in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Dysphagia Severity assessed by Dynamic Imaging Grade of Swallowing Toxicity-Fiberoptic Endoscopic Evaluation of Swallowing (DIGEST-FEES)
研究概览
简要总结
Parkinson's disease (PD) is the second most common neurodegenerative disorder and frequently leads to oropharyngeal dysphagia, a swallowing disorder that strongly affects patient health and quality of life. Dysphagia in PD is associated with aspiration pneumonia, malnutrition, and impaired medication intake, which together represent one of the leading causes of morbidity and premature mortality in these patients. Despite its clinical relevance, the underlying biological mechanisms of dysphagia in PD are not fully understood, and current treatment strategies are limited.
The purpose of this study is to investigate the clinical, biological, and neural determinants of oropharyngeal dysphagia in patients with PD, and to explore compensatory mechanisms of the brain that may counteract swallowing difficulties. We hypothesize that dysphagia in PD is linked not only to disease severity and progression but also to specific biological markers and neural plasticity in the swallowing network.
This is a prospective, cross-sectional observational study including 100 patients with PD. Swallowing function will be systematically assessed using flexible endoscopic evaluation of swallowing (FEES), a gold standard method for detecting penetration and aspiration. Additional clinical data will be collected, including motor and non-motor symptoms, disease severity, and quality of life measures. Biological assessments will include blood-based biomarkers related to inflammation and neurodegeneration. Furthermore, functional magnetic resonance imaging (fMRI) will be used to examine cortical and subcortical activity patterns associated with swallowing and to identify potential compensatory activation in dysphagic and non-dysphagic patients.
By integrating clinical, biological, and imaging approaches, this study aims to provide a comprehensive characterization of dysphagia in PD. The findings are expected to improve the understanding of disease mechanisms and to identify predictors of dysphagia onset and severity. Ultimately, this knowledge may help to guide the development of targeted therapeutic strategies, reduce the risk of severe complications, and improve quality of life for patients with Parkinson's disease.
详细描述
Background and Rationale Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by progressive motor and non-motor symptoms. Among its complications, oropharyngeal dysphagia (OD) is one of the most clinically relevant. Up to 80% of patients develop swallowing impairment during the course of the disease, often without recognizing its presence. Dysphagia is associated with aspiration pneumonia, malnutrition, dehydration, and impaired medication intake, representing a leading cause of morbidity and premature mortality in PD. Despite its high prevalence and impact, the underlying mechanisms of PD-related dysphagia are not fully understood, and current treatment options are limited.
Dysphagia in PD appears to be caused by a combination of central and peripheral factors. On the central level, dopamine deficiency contributes to motor dysfunction, including bradykinesia or freezing of swallowing. Cortical involvement and impaired sensorimotor integration may further reduce swallowing efficiency. On the peripheral level, impaired pharyngeal sensory function and reduced secretion of Substance P have been linked to silent aspiration and insufficient protective reflexes. Evidence from aging research and initial PD studies suggests that compensatory neural activity in cortical swallowing networks may mitigate the risk of aspiration in some patients. However, the clinical, biological, and neural determinants of preserved swallowing function and compensation in PD remain poorly defined.
Objectives and Hypotheses
The overarching objective of this study is to identify biological determinants and neural compensatory mechanisms of oropharyngeal dysphagia in PD. The specific aims are:
To characterize the prevalence, severity, and clinical phenotype of dysphagia in PD using standardized instrumental diagnostics.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •.- Patients with idiopathic Parkinson's disease diagnosed according to the MDS diagnostic criteria
- •Participation possible in all disease stages, regardless of the presence or absence of subjective or objective oropharyngeal dysphagia
- •Cognitive ability sufficient to comply with the study paradigm
- •Daily oral intake of food and fluids (exclusion of patients with exclusive tube feeding)
排除标准
- •Presence of other conditions associated with oropharyngeal dysphagia, such as stroke, head and neck cancer, neuroinflammatory diseases, neuromuscular disorders, or other brain injuries
- •Presence of electronic stimulation devices (e.g., pacemaker, deep brain stimulation) or other contraindications for MRI imaging
- •Diagnosis of asthma or COPD (due to performance of the cough reflex test in "Block 1: Assessment of OD and pharyngeal hyposensitivity")
结局指标
主要结局
Dysphagia Severity assessed by Dynamic Imaging Grade of Swallowing Toxicity-Fiberoptic Endoscopic Evaluation of Swallowing (DIGEST-FEES)
时间窗: Baseline
Swallowing safety and efficiency will be assessed using the Dynamic Imaging Grade of Swallowing Toxicity-Fiberoptic Endoscopic Evaluation of Swallowing (DIGEST-FEES). The DIGEST-FEES is a validated, ordinal rating scale that integrates measures of airway invasion (penetration-aspiration) and pharyngeal residue to generate a composite severity grade of dysphagia. Scores range from 0 (no dysphagia) to 4 (life-threatening dysphagia), with higher scores indicating greater swallowing impairment.
次要结局
- Change in Airway Invasion Severity as Assessed by the Penetration-Aspiration Scale (PAS)(Baseline)
- Neural Activation Patterns (fMRI)(Baseline)
- Electromyography (EMG) of Swallowing Muscles(Baseline)
- Change in Global Cognitive Function as Assessed by the Montreal Cognitive Assessment (MoCA)(Baseline)
- Change in Swallowing-Related Quality of Life as Assessed by the Swallowing Quality of Life Questionnaire (SWAL-QOL)(Baseline)
- Change in Pharyngeal Residue Severity as Assessed by the Yale Residue Severity Scale (YRSS)(Baseline)