BCI With 40Hz Stimulation in Alzheimer's Disease

Ruijin Hospital90 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Alzheimer Dementia (AD)

Interventions

Individualized Stimulation GroupDEVICE

Participants receive 40Hz combined audio-visual stimulation (visual + auditory) for 60 minutes per day, once daily, for 6 consecutive months. In addition, the device performs EEG acquisition and closed-loop feedback adjustment based on preset algorithms. This allows individualized, closed-loop neuromodulation.

Eligibility

Sex: ALLMin age: 50 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (2)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Change in Montreal Cognitive Assessment - Basic (MoCA-B) Score

The primary outcome is the change in MoCA-B score from baseline to 6 months. The MoCA-B is a validated cognitive screening tool for assessing global cognitive function. The score ranges from 0 to 30, with higher scores indicating better cognitive function. The change score (ΔMoCA-B) will be calculated as the 6-month score minus the baseline score. Assessments will be performed by trained neuropsychologists who are blinded to group assignment.

Time frame: Baseline (pre-treatment) and 6 months (end of treatment)

Secondary Outcomes

Change in Auditory Verbal Learning Test (AVLT) Score

The AVLT is a validated neuropsychological test assessing verbal learning and memory function. The test evaluates immediate recall, delayed recall, and recognition. Higher scores indicate better verbal memory performance. Assessments will be performed by trained neuropsychologists blinded to group assignment.

Time frame: Baseline, 3 months, and 6 months

Change in Shape Trails Test (STT-A and STT-B) Score

The STT is a validated neuropsychological test assessing executive function, attention, and psychomotor speed. STT-A primarily measures processing speed, while STT-B measures executive function and task-switching ability. Lower completion time indicates better performance. Assessments will be performed by trained neuropsychologists blinded to group assignment.

Time frame: Baseline, 3 months, and 6 months

Change in Digit Span Test (DST) Score

The DST is a validated neuropsychological test assessing working memory and attention. The test includes forward digit span (attention) and backward digit span (working memory). Higher scores indicate better working memory performance. Assessments will be performed by trained neuropsychologists blinded to group assignment.

Time frame: Baseline, 3 months, and 6 months

Change in Structural MRI Parameters

Changes in structural brain imaging parameters will be assessed using 3T MRI, including gray matter volume, cortical thickness, and hippocampal volume. These parameters will be used to evaluate the neuroprotective effects of the intervention. Imaging data will be analyzed by neuroradiologists blinded to group assignment.