40 Hz Audio-Visual Stimulation Therapy for AD

Condition(s) studied

Investigational drug(s) / intervention(s)

40 Hz Synchronous Audio-Visual Stimulation: Non-invasive audio-visual neuromodulation device generating synchronized 40 Hz light flicker and sound stimulation. Subjects receive 1 session daily, 1 hour per session, for a total of 12 consecutive weeks. After intervention, 24 weeks of observational follow-up without stimulation is performed.

Sham Audio-Visual Stimulation: Identical external device appearance with non-therapeutic low-frequency light and sound signals without 40 Hz gamma oscillation. Administration frequency, duration and operation process are completely consistent with the experimental group, once daily for 1 hour over 12 weeks, followed by 24 weeks of off-treatment follow-up.

Study summary

This is a single-center, parallel-group, double-blind randomized controlled trial conducted at the First Affiliated Hospital of Xiamen University, enrolling 50 participants with Alzheimer's disease (AD)-derived mild cognitive impairment (MCI) or mild AD aged 50-80 years with ≥4 years of education. Subjects must meet diagnostic criteria per Chinese AD guidelines, show medial temporal lobe atrophy on baseline brain MRI, have a reliable caregiver, and be capable of completing all assessments. Exclusion criteria include severe visual/auditory impairment, non-AD dementia, recent neuromodulation therapy, uncontrolled severe systemic diseases, prominent psychiatric disorders, significant cerebral focal lesions on MRI, and other conditions precluding safe participation.

Eligible participants will be randomly assigned to either the 40 Hz audio-visual stimulation group or the placebo group. The intervention lasts 1 hour once daily for 12 weeks, with a total subject follow-up period of 36 weeks (12-week treatment + 24-week observational follow-up). The primary efficacy outcome is the change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) at the end of treatment. Secondary outcomes include changes in Mini-Mental State Examination (MMSE) and ADCS-Activities of Daily Living (ADCS-ADL) scores across all follow-up visits. Exploratory biomarkers cover plasma Aβ42, Aβ40, Tau-217, gamma wave power on electroencephalography (EEG), and repeat Aβ-PET imaging (if previously performed). Cognitive, functional, emotional, EEG, and blood biomarker assessments will be conducted at scheduled time points. Safety monitoring focuses on intervention-related adverse events such as headache and dizziness, with detailed recording of onset, duration and accompanying symptoms.

Statistical analyses will use two-sided tests at α=0.05. Linear mixed models and repeated-measures ANOVA with ANCOVA adjustment for covariates will analyze the primary endpoint; appropriate parametric or nonparametric tests will be applied for secondary and exploratory outcomes. Baseline group balance will be compared via t-tests, Mann-Whitney U tests or chi-square tests. All data processing and statistical modeling will be performed using Python 3.11 and related analytical packages. The trial runs from July 2026 to December 2027.

Eligibility

Primary outcome measure(s)

• Change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) total score at Week 12 (end of intervention) — Baseline and Week 12 (12 weeks after randomization)

Trial sites (1)

More The First Affiliated Hospital of Xiamen University trials in China