Overview

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.

Eligibility

Inclusion Criteria:

1. Adults aged 55 to 90 years.
2. Diagnosed with probable Alzheimer's disease according to NINCDS-ADRDA criteria and DSM-IV criteria for dementia,
3. or 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.