Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Tianjin University | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Temporal Interference Stimulation | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mou Zhehui | Contact | +86 18959257015 | muzhehui@gmail.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Huanhu Hospital | Recruiting | Tianjin | Tianjin Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30378206 | Background | 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. | |
| 37857774 | Background |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Sham Temporal Interference Stimulation | Device | 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 Training | Behavioral | Participants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives. |
|
| General Cognitive Training | Behavioral | Participants will complete general cognitive training tasks involving multiple cognitive domains without specifically emphasizing the primary targeted cognitive process. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | Through study completion, an average of 14 weeks |
| Wessel 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. |
| 37857775 | Background | Violante 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. |
| 28575667 | Background | Grossman 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. |
| 39475597 | Background | Beanato 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. |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D057180 | Frontotemporal Dementia |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D057174 | Frontotemporal Lobar Degeneration |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided