RecruitingNot ApplicableNCT07031687

Effects and Mechanisms of Temporal Interference Brain Stimulation on Memory Function in Preclinical Alzheimer's Disease

Sponsor

Xuanwu Hospital, Beijing

Enrollment

1,200 participants

Start Date

Jul 1, 2025

Study Type

INTERVENTIONAL

Conditions

Alzheimer Disease

Summary

The goal of this clinical trial is to learn if personalized, multimodal imaging-guided, EEG-based closed-loop Temporal Interference Brain Stimulation (TIBS) can improve memory function in individuals with preclinical Alzheimer's Disease (AD). The main questions it aims to answer are: 1. Does personalized TIBS lead to significant changes in functional connectivity strength of hippocampal-cortical networks at the end of the 2-week intervention compared to baseline? 2. What are the short-term (end of 2-week intervention) and medium-to-long-term (4 weeks and 12 weeks post-intervention) effects of personalized TIBS on episodic and working memory, as well as other cognitive domains in preclinical AD? 3. How does personalized TIBS modulate brain activity and connectivity, as measured by EEG power spectra and functional MRI (fMRI) functional connectivity, in preclinical AD? 4. What is the safety profile of personalized TIBS in this population? Researchers will compare participants receiving active personalized TIBS to participants receiving sham (inactive) stimulation to see if TIBS effectively improves memory function and induces neural plasticity. Participants will: 1. Undergo initial screening including neuropsychological assessments and blood p-tau217 testing to identify preclinical AD. 2. Receive either active personalized TIBS or sham stimulation daily for 40 minutes, 6 days a week, for 2 weeks. 3. Have individualized TIBS parameters (e.g., target localization, intensity) determined using baseline structural MRI and DTI. 4. Undergo real-time high-density EEG monitoring during daily stimulation sessions to enable closed-loop adjustment of stimulation parameters. 5. Participate in follow-up assessments at the end of the 2-week intervention, and at 4 weeks and 12 weeks post-intervention. 6. Receive multimodal imaging (sMRI, rs-fMRI, task-fMRI, DTI) and blood biomarker assessments at various time points. 7. Receive Aβ-PET and tau-PET scans, along with comprehensive neuropsychological assessments, at the 12-week follow-up. 8. Have their safety continuously monitored throughout the study.

Eligibility

Min Age: 60 YearsMax Age: 80 Years

Plain Language Summary

Simplified for easier understanding

This study tests whether a type of brain stimulation called temporal interference stimulation can improve memory in people who may be in the very early stages of Alzheimer's disease — before symptoms become obvious. **You may be eligible if...** - You are between 60 and 80 years old - You are right-handed - You have been flagged as being at risk for early Alzheimer's based on the 2024 diagnostic criteria - Your memory tests are in the normal range or show very mild decline - You were recruited through a neurology memory clinic or community program **You may NOT be eligible if...** - You have already been diagnosed with Mild Cognitive Impairment (MCI) or dementia - You have a pacemaker or other implant that might interfere with brain stimulation - You have other neurological conditions Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DEVICEActive TIBS

Participants receive active TIBS targeted at the bilateral hippocampus. Stimulation parameters include a 5 Hz (Theta band) low-frequency modulation envelope, generated by two high-frequency current pairs (e.g., f1=2000 Hz, f2=2005 Hz). Peak-to-peak current intensity for each pair will be 2 mA (or 1 mA per electrode). Stimulation is delivered daily for 40 minutes, 6 days/week, for a total of 2 weeks. Individualized targeting and initial intensity optimization are guided by baseline sMRI and DTI. Real-time high-density EEG monitoring during each daily session (D2-D11) provides feedback on brain activity

DEVICESham TIBS

Participants receive sham stimulation designed to mimic the sensation of active TIBS without therapeutic output. This involves using a sham coil or a device mode with extremely low current intensity (e.g., 0.1-0.2 mA) or brief ramp-up/ramp-down sensations at the beginning and end of sessions, with no effective current delivery during the main stimulation period. The stimulation position and apparent parameters are identical to the active TIBS group to maintain blinding.