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.
Adults aged 55 to 90 years.
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.
mild cognitive impairment/very mild Alzheimer's disease with CDR 0.5-1 and MMSE-II ≥18.
On stable cognitive therapy medications for at least 1 month.
Patients with structural brain lesions detected on brain MRI (e.g., cerebral edema, intracerebral hemorrhage, cerebral infarction, cerebrovascular malformation, brain tumor, etc.).
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).
Patients with a history of epileptic seizures, depression, or psychiatric disorders; patients experiencing visual hallucinations or fluctuating cognitive decline.
Patients with psychiatric disorders outside of the inclusion criteria.
Parallel
Participants receive Neuclare Device while continuing their cognitive medication
DeviceParticipants in this arm receive the Neuclare physical device applied to the cerebral cortex, receiving low-intensity ultrasound stimulation less than 30 minutes per session, three times per week for 4 weeks. This intervention is intended to temporarily improve executive function in patients with mild cognitive impairment and prodromal Alzheimer's disease.
Participants receive Sham Neuclare Device while continuing their cognitive medication
DeviceParticipants in this arm receive a sham version of the Neuclare device, which mimics the appearance and procedure of the active device but does not deliver therapeutic ultrasound. The sham device is applied less than 30 minutes per session, three times per week for 4 weeks, while participants continue their cognitive medication. This arm serves as a control for comparison with the active intervention.
Change in Trail Making Test-A Completion Time from Baseline to Week 5
The primary efficacy outcome is the change in Trail Making Test-A (TMT-A) completion time from baseline to Week 5 after application of the investigational device. Descriptive statistics will be presented for each treatment arm. Between-group comparisons of the change from baseline will be analyzed using ANCOVA with baseline scores as a covariate.
