Synthetic Vasomotion for Glymphatic Enhancement

Prior treatment

• History of significant cardiac disease, including clinically significant arrhythmia, congestive heart failure, unstable angina, myocardial infarction within the prior 12 months, or other conditions judged unsafe for intermittent hypercapnia exposure.
• Active psychiatric condition requiring hospitalization within the prior 12 months.
• Current use of medications known to substantially alter cerebrovascular reactivity or carbon dioxide sensitivity, such as acetazolamide or other carbonic anhydrase inhibitors.

Other illness

• Diagnosis of moderate-to-severe neurocognitive impairment or dementia. Significant pulmonary disease, including chronic obstructive pulmonary disease (COPD), severe asthma requiring daily rescue therapy, restrictive lung disease, or resting oxygen saturation \<92%.
• Untreated or poorly controlled hypertension, defined as systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg at screening.
• Peripheral vascular disease, significant upper-extremity injury, or other conditions that may interfere with peripheral perfusion or physiological monitoring measurements.
• Uncontrolled diabetes mellitus or diabetes-associated complications that may significantly affect autonomic or vascular physiology.
• Active implanted electrical or neurostimulation devices, including cardiac pacemakers, implantable cardioverter-defibrillators (ICDs), deep brain stimulators, cochlear implants, or implanted vagus nerve stimulators.
• Active carotid artery disease, carotid bruits, history of carotid endarterectomy, or other clinically significant cervical vascular abnormalities that may increase risk during cervical nVNS application.
• History of moderate or severe traumatic brain injury, defined as loss of consciousness \>30 minutes or post-traumatic amnesia \>24 hours.
• Known allergy or sensitivity to latex, adhesives, electrode gels, medical tapes, or study device materials that may interfere with safe participation.
• Current acute respiratory infection or other acute illness at the time of study participation.
• Any other medical, neurological, psychiatric, or safety-related condition that, in the opinion of the Principal Investigator, would compromise participant safety, interfere with study procedures, or affect data integrity.

Other

• Symptomatic hypotension, orthostatic hypotension associated with syncope, or clinically significant autonomic dysfunction.
• Claustrophobia or inability to tolerate mask-based breathing procedures. Pregnancy, suspected pregnancy, or lactation in participants of childbearing potential.
• Body mass index (BMI) \>40 kg/m² due to potential effects on respiratory physiology, mask fit, and CO₂ tolerance.

• Parkinson's Disease Group
• Adults aged 60-80 years at the time of enrollment. Clinical diagnosis of early-stage Parkinson's disease and not currently receiving levodopa or other dopaminergic medication.
• Hoehn and Yahr stage I. English-speaking and able to provide informed consent and complete study procedures and questionnaires administered in English.
• Cognitively able to participate in study procedures, as determined by investigator assessment and/or optional cognitive screening measures, when administered.
• Willing and able to comply with all study visits and procedures. Able to tolerate wearing the Applied Cognition GF Monitor, physiological monitoring equipment, face mask, and noninvasive vagus nerve stimulation (nVNS) device for the duration of study procedures.
• Age-Matched Healthy Control Group
• Adults aged 60-80 years at the time of enrollment. No known diagnosis of Parkinson's disease or other major neurodegenerative disorder.
• English-speaking and able to provide informed consent and complete study procedures and questionnaires administered in English.
• Cognitively able to participate in study procedures, as determined by investigator assessment and/or optional cognitive screening measures, when administered.
• Willing and able to comply with all study visits and procedures. Able to tolerate wearing the Applied Cognition GF Monitor, physiological monitoring equipment, face mask, and noninvasive vagus nerve stimulation (nVNS) device for the duration of study procedures.