Effects of Transcutaneous Cervical Vagus Nerve Stimulation on Non-motor Symptoms in Parkinson's Disease

• transcutaneous vagus nerve stimulation (Device): Use the transcutaneous vagus nerve stimulation device on the neck for 30 minutes once a day, at home, every day for 4 weeks.

Primary outcomes

• Change in MDS-NMS total score [Baseline and Week 5 (immediately after the 4-week stimulation period)]: The Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) assesses the severity and frequency of non-motor symptoms in Parkinson's disease across multiple domains. Total score range \[0-832\]; higher scores indicate greater non-motor symptom burden.

Secondary outcomes

• Change in MDS-UPDRS Part I score [Baseline, Week 5, and Week 9]: MDS-UPDRS Part I assesses non-motor aspects of experiences of daily living. 13 items scored 0-4; total range 0-52. Higher scores indicate greater impairment.
• Change in MDS-UPDRS Part II score [Baseline, Week 5, and Week 9]: MDS-UPDRS Part II assesses motor aspects of experiences of daily living. 13 items scored 0-4; total range 0-52. Higher scores indicate greater impairment.
• Change in MDS-UPDRS Part III score [Baseline, Week 5, and Week 9]: MDS-UPDRS Part III is the motor examination. 33 scored items rated 0-4; total range 0-132. Higher scores indicate greater motor impairment.
• Change in Mini-Mental State Examination (MMSE) score [Baseline, Week 5, and Week 9]: The MMSE is a screening measure of global cognitive function. Total range 0-30; higher scores indicate better cognition.
• Change in Montreal Cognitive Assessment (MoCA) score [Baseline, Week 5, and Week 9]: The MoCA is a screening measure of global cognitive function with greater sensitivity to mild impairment. Total range 0-30; higher scores indicate better cognition.
• Change in Pittsburgh Sleep Quality Index (PSQI) global score [Baseline, Week 5, and Week 9]: The PSQI assesses subjective sleep quality over the preceding month. Global score range 0-21; higher scores indicate poorer sleep quality.
• Change in REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score [Baseline, Week 5, and Week 9]: The RBDSQ screens for REM sleep behavior disorder. Total range 0-13; higher scores indicate a greater likelihood of REM sleep behavior disorder.
• Change in Epworth Sleepiness Scale (ESS) score [Baseline, Week 5, and Week 9]: The ESS assesses daytime sleepiness across eight everyday situations. Total range 0-24; higher scores indicate greater daytime sleepiness.
• Change in Geriatric Depression Scale (GDS) score [Baseline, Week 5, and Week 9]: The GDS short form screens for depressive symptoms in older adults. Total range 0-15; higher scores indicate more depressive symptoms.
• Change in State-Trait Anxiety Inventory (STAI) State subscale score [Baseline, Week 5, and Week 9]: The STAI Form Y-1 measures state anxiety. 20 items; total range 20-80. Higher scores indicate greater anxiety. The STAI Form Y-2 measures trait anxiety. 20 items; total range 20-80. Higher scores indicate greater anxiety.
• Change in GIDS-PD score [Baseline, Week 5, and Week 9]: The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) assesses the severity and impact of gastrointestinal symptoms. Total score range \[1-108\]; higher scores indicate greater gastrointestinal dysfunction.
• Number of participants with adverse events and serious adverse events [From informed consent through Week 9]: Adverse events and serious adverse events are recorded from the time of informed consent through the final study visit and graded using NCI-CTCAE. Events of particular interest include application-site skin reactions, headache, dizziness, nausea, fatigue, palpitations, and changes in blood pressure or heart rate.
• Adherence to home-based stimulation [Over the 4-week stimulation period (Week 1 to Week 5)]: Adherence is calculated as the number of days the device was actually used divided by the 28 planned days, multiplied by 100, derived from the device's internal timestamp log and the participant diary or smartphone application.

Sex: All, ages: 20 Years to 79 Years

Inclusion Criteria:

* Idiopathic Parkinson's disease diagnosed according to the UK Brain Bank criteria and the MDS Clinical Diagnostic Criteria for Parkinson's Disease
* Hoehn and Yahr stage I to III, assessed in the ON state
* Aged 20 to 79 years
* If taking antiparkinsonian medication (e.g., levodopa, dopamine agonists), on a stable regimen for at least 4 weeks before enrollment
* Willing to participate voluntarily and able to provide written informed consent
* Able to attend the scheduled study visits and to perform the home-based intervention throughout the study period

Exclusion Criteria:

* Secondary parkinsonism (e.g., vascular, drug-induced, multiple system atrophy) or an atypical parkinsonian syndrome
* Presence of a deep brain stimulation (DBS) device, or planned DBS surgery during the study period
* Active cardiac arrhythmia, or presence of an implanted cardiac pacemaker or an implantable cardioverter-defibrillator (ICD), which are contraindications to vagus nerve stimulation
* History of open surgery of the neck, or history of cervical nerve injury
* Active epilepsy, or a seizure within the past year
* Dementia, or inability to provide independent informed consent
* Active psychiatric illness, including schizophrenia, acute-phase bipolar disorder, or severe depression with suicidal risk
* Intracranial lesions such as stroke, brain tumor, or hydrocephalus
* Contraindications to MRI, such as cerebral aneurysm clips, cochlear implants, or other ferromagnetic foreign bodies; metallic joint prostheses are assessed on a case-by-case basis
* Pregnant or breastfeeding women, and women of childbearing potential who plan to become pregnant during the study or who are not using adequate contraception
* Participation in another clinical trial within the past 3 months
* History of alcohol or substance abuse within the past 6 months
* Any other condition that, in the judgment of the investigator, makes the participant unsuitable for study participation