Neuclare Device for Temporary Improvement of Executive Function in Patients With Mild Cognitive Impairment and Prodromal Alzheimer's Disease

A Prospective, Multicenter, Randomized, Double-Blind, Parallel-Group, Confirmatory Clinical Trial to Verify the Efficacy and Safety of the Cognitive Improvement Effect on Executive Function in Medication-Treated Patients With Mild Cognitive Impairment and Prodromal Alzheimer's Disease Using the Neuclare Physical Device for Medical Use

This study is a multicenter, randomized, double-blind, parallel-group, prospective confirmatory clinical trial designed to evaluate whether the Neuclare medical device can temporarily improve executive function (planning and problem-solving abilities) in adults with mild cognitive impairment or very early Alzheimer's disease.

Participants will continue their current medication and be randomly assigned to receive either the Neuclare device (treatment group) or a sham device (control group). The device will be applied to the brain three times per week for four weeks. Both participants and study staff are blinded to the group assignment. Safety and adverse events will be closely monitored throughout the study.

During the trial, assessments will include attention, cognitive function, daily living activities, brain imaging (Amyloid PET-CT), blood biomarkers, and quality of life (EQ-5D-5L).

The goal of this study is to determine whether the Neuclare device, in combination with standard medication, can safely provide temporary improvements in executive function.

Inclusion Criteria:

1. Adults aged 55 to 90 years.
2. Diagnosed with mild cognitive impairment (MCI) or early Alzheimer's disease according to the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria.
3. mild cognitive impairment/very mild Alzheimer's disease with CDR 0.5-1 and MMSE-II ≥18.
4. On stable cognitive therapy medications for at least 1 month.
5. Voluntary participation with signed informed consent.

Exclusion Criteria:

1. Patients with structural brain lesions detected on brain MRI (e.g., cerebral edema, intracerebral hemorrhage, cerebral infarction, cerebrovascular malformation, brain tumor, etc.).
2. Patients with uncontrolled metabolic disorders such as thyroid dysfunction, hypoglycemia, or hepatic/renal impairment, or those on long-term medications that may cause cognitive impairment (e.g., anticholinergic drugs).
3. Patients with a history of epileptic seizures, depression, or psychiatric disorders; patients experiencing visual hallucinations or fluctuating cognitive decline.
4. Patients with psychiatric disorders outside of the inclusion criteria.
5. Patients with a history of severe diseases such as cancer or tuberculosis.
6. Patients with a history of or currently taking psychoactive drugs or medications affecting the central or peripheral nervous system.
7. Patients with contact dermatitis or other skin hypersensitivity conditions.
8. Patients with fever ≥ 40°C as measured by tympanic temperature.
9. Patients who have experienced bleeding within the past 3 months due to procedures or surgeries that may affect vital signs.
10. Patients unable to undergo MRI.
11. Pregnant patients.
12. Patients with clinical brain calcification observed on computed tomography (CT) scans.
13. Patients with known allergies to contrast agents such as Definity or Gadovist.
14. Any other condition deemed by the investigator to make participation in the clinical trial inappropriate.