BCI With 40Hz Stimulation in Alzheimer's Disease

Shanghai Jiao Tong University

Status: Enrolling

Conditions: Alzheimer Dementia (AD)

Treatments: Device: Sham Stimulation Group; Device: 40Hz Stimulation Group; Device: Individualized Stimulation Group

Study type: Interventional

Funder types: Other

Identifiers

NCT07618481

2026222

Details and patient eligibility

About

This study aims to evaluate the efficacy and safety of non-invasive brain-computer interface (BCI) neuromodulation technique combined with 40Hz audio-visual stimulation on cognitive function in patients with Alzheimer's disease (AD). This is a single-center, randomized, double-blind, sham-controlled trial. A total of 90 participants with Aβ-PET positive AD diagnosed according to NIA-AA criteria will be enrolled and randomly assigned to three groups in a 1:1:1 ratio: (1) 40Hz stimulation group (fixed 40Hz audio-visual stimulation, 60 minutes daily for 6 months), (2) individualized stimulation group (closed-loop BCI with real-time EEG feedback to adjust stimulation parameters, 60 minutes daily for 6 months), and (3) sham stimulation group (inactive stimulation, same duration). The primary outcome is the change in MoCA-B score from baseline to 6 months. Secondary outcomes include changes in cognitive domain-specific assessments (AVLT, STT, DST), multimodal brain imaging, EEG parameters, peripheral blood AD biomarkers, safety, tolerability, and comparison of efficacy between open-loop and closed-loop stimulation.

Enrollment: 90 estimated patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of Alzheimer's disease according to the NIA-AA 2018 diagnostic criteria.
2. Age between 50 and 80 years, inclusive.
3. Positive Aβ-PET scan result.
4. Has a stable caregiver who can assist with daily stimulation intervention.
5. Chronic medical conditions stable for at least 30 days.
6. Adequate vision and hearing to perform testing (at minimum, ability to perceive light and communicate in daily conversation).
7. Good mobility (able to walk independently or with assistive devices).
8. Willing and able to provide voluntary signed informed consent.

Exclusion criteria

1. History of epilepsy or seizure disorder.
2. Inability to undergo MRI or presence of significant abnormalities on MRI screening.
3. Geriatric Depression Scale (GDS) score > 6.
4. Current suicidal ideation or suicide attempt within the past 6 months.
5. Other major neurological disorders, including but not limited to: dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, Creutzfeldt-Jakob disease, Down syndrome, or mixed dementia; other neurodegenerative diseases (Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, etc.); history of severe brain infection (meningitis/encephalitis) or multiple concussions; metabolic/systemic diseases causing cognitive impairment (syphilis, vitamin B12 or folate deficiency, etc.).
6. Psychiatric disorders.
7. Severe cardiac disease, chronic liver/kidney/respiratory disease, or uncontrolled diabetes mellitus or thyroid disease.
8. History of drug or alcohol abuse within the past 12 months.
9. Current exposure to anti-Aβ antibody immunotherapies.
10. Current use of memantine within 30 days prior to intervention.
11. Life expectancy < 24 months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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90 participants in 3 patient groups

40Hz Stimulation Group

Experimental group

Description:

Fixed 40Hz combined audio-visual stimulation, 60 minutes per day, once daily, for 6 consecutive months.

Treatment:

Device: 40Hz Stimulation Group

Individualized Stimulation Group

Experimental group

Description:

40Hz combined audio-visual stimulation with EEG-based closed-loop feedback adjustment, 60 minutes per day, once daily, for 6 consecutive months.

Treatment:

Device: Individualized Stimulation Group

Sham Stimulation Group

Sham Comparator group

Description:

Identical appearance and operation as the active device, but without effective individualized audio-visual stimulation. Only low-intensity, randomized flashes and audio cues are delivered.

Treatment:

Device: Sham Stimulation Group