Transcutaneous Auricular Vagus Nerve Stimulation in Type 2 Diabetes With Mild Cognitive Impairment

Prior treatment

• Concomitant use of GLP-1 receptor agonists, Alzheimer's disease medications, anti-Parkinson's medications, antiepileptic drugs, or antipsychotic drugs within 3 months prior to screening
• Concurrent major illnesses, such as active or untreated malignancies, or malignancies in clinical remission for less than 5 years.

Other illness

• Presence of dementia-related neurological disorders; current or history of clinically significant psychiatric disorders within the past 2 years (e.g., schizophrenia, bipolar disorder, major depressive disorder, generalized anxiety disorder, personality disorders)
• CNS diseases, including traumatic brain injury, intracranial hemorrhage, acute cerebral infarction, etc
• Severe sinusitis, nasal and sinus polyps, space-occupying lesions such as skull base or nasopharyngeal tumors; congenital diseases or history of trauma of the nose, maxillofacial region, or skull base that affect olfactory function; presence of upper respiratory tract infection symptoms (e.g., nasal congestion, rhinorrhea, fever) on the day of the MRI scan
• Acute complications of diabetes, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, hypoglycemic coma, etc
• Contraindications for MRI scans (e.g., implanted metallic prostheses, claustrophobia); presence of cardiac pacemakers or other implantable medical devices; severe infection or ulceration of the auricular skin
• History of alcohol abuse, defined as an average weekly alcohol consumption exceeding 21 units for males and 14 units for females (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of distilled spirits/liquor)
• Any other conditions or factors that, in the opinion of the investigator, may confound the efficacy or safety evaluation of the study, making the participant unsuitable for enrollment

Lab values

• Severe impairment of major organ function (e.g., heart, liver, kidneys), including any of the following: ALT and/or AST \> 3×ULN. eGFR \< 45 mL/min/1.72 m² (CKD-EPI). History of unstable angina, myocardial infarction, or NYHA Class II or higher heart failure within 3 months prior to screening

Other

• Pregnant or lactating women

• Type 2 diabetes mellitus
• Meets criteria for mild cognitive impairment
• Aged 40 to 75 years, with no gender restrictions
• HbA1c levels between 6.5% and 9.0%
• At least 6 years of formal education
• Able to cooperate with and complete all cognitive and functional assessments
• Right-handed
• Voluntary provision of written informed consent