Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age45-85
SponsorTianjin Huanhu Hospital
About this trial
This study aims to evaluate the efficacy and safety of temporal interference stimulation (TIS), a non-invasive neuromodulation technique, in improving cognitive function in patients with cognitive impairment. TIS uses two high-frequency currents applied transcranially, which intersect within the brain to generate a low-frequency modulation field. This technique selectively modulates deep brain regions while minimizing the stimulation of superficial cortical layers.
Participants will undergo individualized MRI-based modeling to determine the optimal electrode placement and stimulation parameters. The intervention consists of 10 stimulation sessions over a period of 14 days, using either active TIS or sham stimulation. Cognitive assessments, EEG recordings, and functional MRI scans will be conducted at baseline; 5 days after intervention initiation; at the end of the 10-day intervention; and during follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention to evaluate both immediate and long-term effects on cognitive performance and neural activity.
The study aims to determine whether TIS can serve as a feasible and effective neuromodulation strategy for individuals with cognitive impairment.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
meets the criteria for probable AD and MCI due to AD as defined by the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines;
Positive amyloid biomarker (amyloid PET or CSF tTau/Aβ 42);
Positive tau biomarker (tau-PET or CSF pTau181);
AD-related standard treatments (acetyl cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists) taken at a stable dose for at least 12 weeks prior to baseline.
Disqualifiers
Diagnosis of other types of dementia or major neurological disorders (e.g., stroke, epilepsy, Lewy body dementia, vascular dementia, Parkinson's disease dementia, Huntington's disease).
Major psychiatric disorders such as severe depression or anxiety.
Severe systemic or organ dysfunction (e.g., heart failure III-IV, liver cirrhosis, renal failure).
Use of medications that significantly affect cognition (e.g., anticholinergics, sedatives), unless approved by the physician.
Trial design
Design model
Parallel
Treatments tested in this trial
Temporal Interference Stimulation
DeviceTemporal interference stimulation will be delivered using two high-frequency alternating currents at 2000 Hz and 2100 Hz, generating a low-frequency envelope. Stimulation will be delivered in a theta-burst-like pattern with 2 seconds on and 8 seconds off. Frontal and temporal targets will be stimulated sequentially. In the sham-controlled group, participants will receive active stimulation during Days 6-10 following 5 days of sham stimulation. In the active stimulation groups, participants will receive active stimulation throughout the entire 10-day intervention period. Two sessions will be administered per day, with each session lasting 40 minutes.
Sham Temporal Interference Stimulation
DeviceSham stimulation will use two identical high-frequency currents of 2000 Hz and 2000 Hz, producing no frequency difference and no modulation envelope. The stimulation timing, electrode placement, and procedures will be consistent with active stimulation to maintain blinding. In the sham-controlled group, sham stimulation will be administered during Days 1-5 before switching to active stimulation.
Targeted Cognitive Training
BehavioralParticipants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives.
General Cognitive Training
BehavioralParticipants will complete general cognitive training tasks involving multiple cognitive domains without specifically emphasizing the primary targeted cognitive process.
Treatment groups
60 Participants
are divided into 3 treatment groupsGroup A: Sham TIS + Active TIS + Targeted Cognitive TrainingSham comparator 3 interventions
Group B: Active TIS + Active TIS + Targeted Cognitive TrainingExperimental treatment 2 interventions
Group C: Active TIS + Active TIS + General Cognitive TrainingActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Changes from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
Measures global cognitive function. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a clinician-administered scale commonly used to assess cognitive performance in individuals with cognitive impairment and dementia. Full Scale Name: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Typical Total Score Range: 0 to 70. Higher Scores Mean: Greater cognitive impairment (worse cognitive performance).
Time frame
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.Secondary outcomes
1
Cross-frequency Neural Oscillations
Electrophysiological indices of cross-frequency neural interactions will be quantified using electroencephalography (EEG). Measures will include phase-amplitude coupling (PAC) between low-frequency and high-frequency bands (e.g., theta-gamma and alpha-gamma coupling), cross-frequency coherence, and power modulation across frequency bands. These metrics reflect the integrity of neural communication and network coordination within cognition-related brain systems.
Time frame
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.2
Change from baseline in resting-state frontal-temporal EEG functional connectivity strength
After EEG preprocessing, frequency-band decomposition, and functional connectivity analysis, functional connectivity strength within frontal regions, within temporal regions, and between frontal and temporal regions will be calculated.
Time frame
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.3
Changes from Baseline in Frontal and Temporal Gray Matter Density (sMRI)
Evaluation of changes in gray matter density or volume within frontal and temporal brain regions, quantified using structural Magnetic Resonance Imaging (sMRI). This measure assesses the structural integrity and potential neuroplastic changes, including cortical thinning or gray matter increase, in brain regions critically involved in executive function, language processing, and memory-related cognitive processes.
Time frame
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.4
Changes from Baseline in Cortical Thickness (sMRI)
Evaluation of changes in cortical thickness across various brain regions, quantified using structural Magnetic Resonance Imaging (sMRI). This measure assesses the integrity and potential thinning or thickening of the cerebral cortex.
Time frame
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.Sponsors and contacts
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Tianjin Huanhu Hospital
Lead sponsor
Tianjin University
Collaborator
Source ClinicalTrials.gov