Amnestic Mild Cognitive Impairment - aMCITISNCT07643363
Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment
A study testing Temporal Interference Stimulation, Targeted Cognitive Training and General Cognitive Training in people with Amnestic Mild Cognitive Impairment - aMCI and AD-MCI, run by Tianjin Huanhu Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 85 years
- Conditions the study is for
- Amnestic Mild Cognitive Impairment - aMCI, AD-MCI, AD - Alzheimer's Disease
- What is being tested?
- Temporal Interference Stimulation, Targeted Cognitive Training and General Cognitive Training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2026to Jun 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- meets the criteria for probable bvFTD as defined by the revised diagnostic criteria for the behavioural variant of frontotemporal dementia (2011), or PPA as defined by the Classification of primary progressive aphasia and its variants (2011);
- Optional genetic confirmation of FTD-related pathogenic mutations (if available).
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- Aged between 45 and 85 years, inclusive; no gender limitation.
- Right-handed.
- Education level ≥ 3 years.
- Mini-Mental State Examination (MMSE) score ≥ 11.
- Clinical Dementia Rating (CDR) score of 1 or 2.
- with a reliable caregiver
- Able to cooperate with cognitive assessments and cognitive training procedures.
- Full understanding of the study, voluntary participation, and provision of written informed consent approved by the Ethics Committee.
Who cannot join
- 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.
- Presence of metal implants incompatible with MRI or TIS (e.g., pacemakers, deep brain stimulators).
- Skull defects or cranial abnormalities.
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- Inability to tolerate EEG or head stabilization.
- Severe visual or hearing impairment preventing task performance.
- History of alcohol or drug abuse.
- Participation in another clinical trial within the past 3 months.
- Current or recent treatment with anti-amyloid monoclonal antibodies (e.g., lecanemab, donanemab).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tianjin Huanhu Hospital
Tianjin, Tianjin Municipality
Li Pan, Director, +86 13114881943, doc_panpan@163.com
About this study
Official title: A Randomized, Sham-Controlled Trial of Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment
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.
- Being tested
- Temporal Interference Stimulation, Sham Temporal Interference Stimulation, Targeted Cognitive Training, General Cognitive Training
- Keywords
- Temporal Interference Stimulation, Alzheimer's Disease, Frontotemporal Dementia
- Medical subject headings
- Alzheimer Disease, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temporal Interference StimulationDevice
Temporal 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 StimulationDevice
Sham 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 TrainingBehavioural
Participants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives.
General Cognitive TrainingBehavioural
Participants will complete general cognitive training tasks involving multiple cognitive domains without specifically emphasizing the primary targeted cognitive process.
| Study group | Role | What they receive |
|---|---|---|
| Sham TIS + Active TIS + Targeted Cognitive Training | Sham comparator | Participants will receive sham temporal interference stimulation during the first 5 days, followed by active temporal interference stimulation during the next 5 days. Targeted cognitive training will be administered during the intervention period. Receives: Device: Temporal Interference Stimulation; Device: Sham Temporal Interference Stimulation; Behavioral: Targeted Cognitive Training |
| Active TIS + Active TIS + Targeted Cognitive Training | Experimental | Participants will receive active temporal interference stimulation during the first 5 days and the next 5 days. Targeted cognitive training will be administered during the intervention period. Receives: Device: Temporal Interference Stimulation; Behavioral: Targeted Cognitive Training |
| Active TIS + Active TIS + General Cognitive Training | Active comparator | Participants will receive active temporal interference stimulation during the first 5 days and the next 5 days. General cognitive training will be administered during the intervention period. Receives: Device: Temporal Interference Stimulation; Behavioral: General Cognitive Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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 (17)
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
Changes from baseline in ALFF
Resting-state fMRI will be used to quantify changes in the amplitude of low-frequency fluctuations (ALFF) within frontal and temporal brain regions following intervention.
Measured: 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.
Changes from baseline in ReHo
Resting-state fMRI data will be analyzed to evaluate changes in regional homogeneity (ReHo), reflecting local synchronization of spontaneous neural activity within frontal and temporal regions.
Measured: 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.
Changes from baseline in resting-state functional connectivity
Evaluation of changes in resting-state functional connectivity between frontal and temporal brain regions using fMRI, reflecting synchronized neural activity within memory and attention-related networks.
Measured: 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.
Changes from baseline in FA
Evaluation of changes in fractional anisotropy (FA) in white matter tracts using diffusion tensor imaging (DTI), reflecting directional water diffusion and white matter integrity.
Measured: 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.
Changes from baseline in MD
Evaluation of changes in mean diffusivity (MD) in white matter tracts using DTI, reflecting overall magnitude of water diffusion.
Measured: 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.
Changes from baseline in AD
Evaluation of changes in axial diffusivity (AD) in white matter tracts using DTI, reflecting diffusion along the principal axis of fibers.
Measured: 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.
Changes from baseline in RD
Evaluation of changes in radial diffusivity (RD) in white matter tracts using DTI, reflecting diffusion perpendicular to fiber orientation and potential demyelination.
Measured: 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.
Changes from Baseline in Mini-Mental State Examination (MMSE) Score
Measures global cognitive function. Full Scale Name: Mini-Mental State Examination (MMSE) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
Measured: 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.
Changes from Baseline in Montreal Cognitive Assessment - Basic (MoCA-B) Score
Measures global cognitive function. Full Scale Name: Montreal Cognitive Assessment - Basic (MoCA-B) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
Measured: 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.
Changes from Baseline in Clinical Dementia Rating (CDR) Score
Measures global cognitive and functional status using the Clinical Dementia Rating (CDR) scale, which assesses cognitive performance and daily functioning across multiple domains, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
The CDR provides a global rating of dementia severity based on structured interviews with the participant and an informant, reflecting overall cognitive impairment and functional impact.
Measured: 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.
Changes from Baseline in Zarit Caregiver Burden Interview (ZBI) Score
Assesses perceived caregiver burden. The Zarit Caregiver Burden Interview (ZBI) is a widely used, caregiver-reported questionnaire designed to evaluate the level of burden experienced by individuals providing care to persons with cognitive impairment or other chronic conditions.
The scale assesses emotional, physical, social, and financial aspects of caregiver strain.
Total Score Range: 0 to 88. Higher Scores Mean: Greater caregiver burden. Change in ZBI score from baseline to each assessment time point will be analyzed.
Measured: 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.
Changes from Baseline in AD Molecular Pathologies and Blood Biomarkers
Plasma concentrations of Alzheimer's disease-related biomarkers-including the Aβ42/40 ratio, phosphorylated tau-217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-will be quantified using validated immunoassay platforms. These biomarkers reflect amyloid pathology, tau phosphorylation, axonal injury, and astroglial activation, respectively. Changes from baseline will be assessed to evaluate peripheral biochemical responses to the intervention.
Measured: 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.
Incidence and Severity of Adverse Events (AEs)
Monitoring and reporting of all adverse events and serious adverse events related to the intervention, including their frequency, severity, and relationship to the study intervention
Measured: Through study completion, an average of 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study start1 Jul 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Amnestic Mild Cognitive Impairment - aMCIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Huanhu Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tianjin University
- Responsible party
- Principal investigator, Pan Li, Tianjin Huanhu Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07643363
- Sponsor's protocol ID
- TJHH-CI-TIS-2025-12
- Acronym
- TIS
- Status last verified
- Jun 2026
- First submitted
- 1 Jun 2026
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li LM, Violante IR, Leech R, Ross E, Hampshire A, Opitz A, Rothwell JC, Carmichael DW, Sharp DJ. Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation. Hum Brain Mapp. 2019 Feb 15;40(3):904-915. doi: 10.1002/hbm.24420. Epub 2018 Oct 30.
PubMed 30378206Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.
PubMed 37857774Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
PubMed 37857775Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
PubMed 28575667Beanato E, Moon HJ, Windel F, Vassiliadis P, Wessel MJ, Popa T, Pauline M, Neufeld E, De Falco E, Gauthier B, Steiner M, Blanke O, Hummel FC. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci Adv. 2024 Nov;10(44):eado4103. doi: 10.1126/sciadv.ado4103. Epub 2024 Oct 30.
PubMed 39475597
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Sham-Controlled Trial of Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment
- ClinicalTrials.gov ID
- NCT07643363
- Acronym / sponsor ID
- TIS / TJHH-CI-TIS-2025-12
- Keywords
- Temporal Interference Stimulation, Alzheimer's Disease, Frontotemporal Dementia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Tianjin Huanhu HospitalUniversity, hospital or other
- Collaborators
- Tianjin University
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 11 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sham TIS + Active TIS + Targeted Cognitive Training | Sham comparator | Device: Temporal Interference Stimulation, Device: Sham Temporal Interference Stimulation, Behavioral: Targeted Cognitive TrainingParticipants will receive sham temporal interference stimulation during the first 5 days, followed by active temporal interference stimulation during the next 5 days. Targeted cognitive training will be administered during the intervention period. |
| Active TIS + Active TIS + Targeted Cognitive Training | Experimental | Device: Temporal Interference Stimulation, Behavioral: Targeted Cognitive TrainingParticipants will receive active temporal interference stimulation during the first 5 days and the next 5 days. Targeted cognitive training will be administered during the intervention period. |
| Active TIS + Active TIS + General Cognitive Training | Active comparator | Device: Temporal Interference Stimulation, Behavioral: General Cognitive TrainingParticipants will receive active temporal interference stimulation during the first 5 days and the next 5 days. General cognitive training will be administered during the intervention period. |
Who may qualify
- Ages
- 45 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- meets the criteria for probable bvFTD as defined by the revised diagnostic criteria for the behavioural variant of frontotemporal dementia (2011), or PPA as defined by the Classification of primary progressive aphasia and its variants (2011);
Key exclusion criteria (11 listed)
- 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.
- Presence of metal implants incompatible with MRI or TIS (e.g., pacemakers, deep brain stimulators).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temporal Interference StimulationTemporal 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. | Device | Active TIS + Active TIS + General Cognitive Training, Active TIS + Active TIS + Targeted Cognitive Training, Sham TIS + Active TIS + Targeted Cognitive Training |
| Sham Temporal Interference StimulationSham 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. | Device | Sham TIS + Active TIS + Targeted Cognitive Training |
| Targeted Cognitive TrainingParticipants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives. | Behavioural | Active TIS + Active TIS + Targeted Cognitive Training, Sham TIS + Active TIS + Targeted Cognitive Training |
| General Cognitive TrainingParticipants will complete general cognitive training tasks involving multiple cognitive domains without specifically emphasizing the primary targeted cognitive process. | Behavioural | Active TIS + Active TIS + General Cognitive Training |
Primary outcome
Changes from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
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.
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).
17 secondary outcomes
Cross-frequency Neural Oscillations
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.
Change from baseline in resting-state frontal-temporal EEG functional connectivity strength
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.
Changes from Baseline in Frontal and Temporal Gray Matter Density (sMRI)
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.
Changes from Baseline in Cortical Thickness (sMRI)
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.
Changes from baseline in ALFF
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.
Changes from baseline in ReHo
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.
Changes from baseline in resting-state functional connectivity
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.
Changes from baseline in FA
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.
Changes from baseline in MD
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.
Changes from baseline in AD
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.
Changes from baseline in RD
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.
Changes from Baseline in Mini-Mental State Examination (MMSE) Score
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.
Changes from Baseline in Montreal Cognitive Assessment - Basic (MoCA-B) Score
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.
Changes from Baseline in Clinical Dementia Rating (CDR) Score
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.
Changes from Baseline in Zarit Caregiver Burden Interview (ZBI) Score
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.
Changes from Baseline in AD Molecular Pathologies and Blood Biomarkers
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.
Incidence and Severity of Adverse Events (AEs)
Time frame: Through study completion, an average of 14 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Background: PubMed 30378206Li LM, Violante IR, Leech R, Ross E, Hampshire A, Opitz A, Rothwell JC, Carmichael DW, Sharp DJ. Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation. Hum Brain Mapp. 2019 Feb 15;40(3):904-915. doi: 10.1002/hbm.24420. Epub 2018 Oct 30.
- Background: PubMed 37857774Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.
- Background: PubMed 37857775Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
- Background: PubMed 28575667Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Temporal Interference Stimulation, Targeted Cognitive Training and General Cognitive Training in people with Amnestic Mild Cognitive Impairment - aMCI and AD-MCI, run by Tianjin Huanhu Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mou Zhehui (+86 18959257015, muzhehui@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07643363, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.