BCI With 40Hz Stimulation in Alzheimer's Disease

Official title

EEG-Based Non-Invasive Brain-Computer Interface Combined With 40Hz Audio-Visual Stimulation for Cognitive Function in Patients With Alzheimer's Disease: A Randomized Double-Blind Controlled Study

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.

Interventions

• Device 40Hz Stimulation Group
  Participants receive fixed 40Hz combined audio-visual stimulation (visual + auditory) for 60 minutes per day, once daily, for 6 consecutive months. The stimulation parameters are fixed and do not adjust based on EEG feedback.
• Device Individualized Stimulation Group
  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.
• Device Sham Stimulation Group
  Participants receive sham stimulation using a device identical in appearance and weight to the active device. The sham device does not output effective individualized audio-visual stimulation; only low-intensity, randomized flashes and audio cues are delivered.

Primary outcome measures

• Change in Montreal Cognitive Assessment - Basic (MoCA-B) Score [Time frame: Baseline (pre-treatment) and 6 months (end of treatment)]

Secondary outcome measures (10)

• Change in Auditory Verbal Learning Test (AVLT) Score [Time frame: Baseline, 3 months, and 6 months]
• Change in Shape Trails Test (STT-A and STT-B) Score [Time frame: Baseline, 3 months, and 6 months]
• Change in Digit Span Test (DST) Score [Time frame: Baseline, 3 months, and 6 months]
• Change in Structural MRI Parameters [Time frame: Baseline and 6 months]
• Change in Functional MRI (fMRI) Parameters [Time frame: Baseline and 6 months]
• Change in Peripheral Blood Alzheimer's Disease Biomarkers [Time frame: Baseline and 6 months]
• Change in Aβ-PET Standardized Uptake Value Ratio (SUVR) [Time frame: Baseline and 6 months]
• Change in tau-PET Standardized Uptake Value Ratio (SUVR) [Time frame: Baseline and 6 months]
• Incidence of Serious Adverse Events (SAEs) [Time frame: Baseline through 6 months (entire study period)]
• Incidence of Adverse Events (AEs) [Time frame: Baseline through 6 months (entire study period)]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• History of epilepsy or seizure disorder.
• Inability to undergo MRI or presence of significant abnormalities on MRI screening.
• Geriatric Depression Scale (GDS) score > 6.
• Current suicidal ideation or suicide attempt within the past 6 months.
• 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.).
• Psychiatric disorders.
• Severe cardiac disease, chronic liver/kidney/respiratory disease, or uncontrolled diabetes mellitus or thyroid disease.
• History of drug or alcohol abuse within the past 12 months.
• Current exposure to anti-Aβ antibody immunotherapies.
• Current use of memantine within 30 days prior to intervention.
• Life expectancy < 24 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai
• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07618481 · 2026222

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗