Mild Cognitive Impairment (MCI)
Conditions
Brief summary
This study aims to evaluate whether individualized hippocampal transcranial temporal interference stimulation (tTIS) combined with Tai Chi training can improve cognitive function and dual-task performance in individuals with mild cognitive impairment. Participants will be randomly assigned to receive either active or sham individualized tTIS combined with Tai Chi training for 8 weeks. The study will also investigate changes in brain structure and function using neuroimaging and assess whether the intervention effects are maintained during follow-up.
Detailed description
This is a randomized, quadruple-blind, sham-controlled, parallel-group trial involving approximately 120 individuals aged 60-80 years with mild cognitive impairment. Participants will be randomly assigned to receive either active or sham individualized transcranial temporal interference stimulation (tTIS) combined with Tai Chi training for 8 weeks, three sessions per week. Individualized tTIS will target the left hippocampus based on participant-specific T1-weighted MRI and finite element modeling, using a 5-Hz interference frequency generated by 2000- and 2005-Hz carrier frequencies at an intensity of 2 mA for 20 minutes per session; each Tai Chi session will last approximately 60 minutes. Global cognition, episodic memory, neuropsychiatric symptoms, functional status, and health-related quality of life will be assessed at baseline, after the 8-week intervention, and at a 16-week post-intervention follow-up. Working memory and executive control, dual-task performance, and neuroimaging outcomes will be assessed at baseline and after the 8-week intervention, with safety, tolerability, and blinding effectiveness monitored throughout the study.
Interventions
Active tTIS delivered via surface electrodes targeting the hippocampus. Parameters: 2 mA baseline-to-peak intensity, 20-minute duration with 30-second ramp-up and ramp-down. The stimulation protocol is individualized based on each participant's T1-weighted structural MRI using finite element modeling to optimize electric field distribution to the hippocampal target. Stimulation will be administered three times per week for 8 weeks.
DEVICEPlacebo Transcranial Temporal Interference Stimulation
Placebo stimulation delivered using the same electrode placement and parameters as active stimulation. To mimic the sensory experience without effective neuromodulation, active current is delivered only during the 30-second ramp-up and ramp-down periods. During the 20-minute stimulation period, no current is delivered. Participants are unable to distinguish sham from active stimulation based on sensation. Sham stimulation will be administered three times per week for 8 weeks.
BEHAVIORALTai Chi Training
Participants will receive standardized Tai Chi training for approximately 60 minutes per session, three sessions per week for 8 weeks. The same Tai Chi training protocol will be provided to participants in both study arms.
Sponsors
Shanghai University of Sport
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 60-80 years * Community-dwelling * Montreal Cognitive Assessment (MoCA) score \< 26 * Clinical Dementia Rating (CDR) score = 0.5 * Activities of Daily Living (ADL) score \< 26 (largely intact daily function) * Does not meet criteria for dementia diagnosis (based on DSM-5 or NIA-AA criteria) * No contraindications for MRI examination (no metallic implants, no claustrophobia) * Able to provide written informed consent
Exclusion criteria
* Neurological conditions that may cause cognitive decline (e.g., cerebrovascular disease, encephalitis, Parkinson's disease, Huntington's disease) * Severe visual, auditory, or language impairments preventing completion of neuropsychological assessments * Severe depression (Geriatric Depression Scale \> 10) or other major psychiatric disorders * History of seizures or epilepsy * Previous deep brain stimulation or electroconvulsive therapy within 6 months * Alcohol or substance dependence * Concurrent participation in another interventional clinical trial * Contraindications for non-invasive brain stimulation: electronic or ferromagnetic implants, non-MRI compatible metal implants, history of seizures, pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assessment (MoCA) Score | Baseline, Week 8, and Week 24 | Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). The total score ranges from 0 to 30, with higher scores indicating better cognitive function. Changes from baseline will be evaluated after the intervention and at follow-up. |
| Change in Mini-Mental State Examination (MMSE) Score | Baseline, Week 8, and Week 24 | Global cognitive function will also be assessed using the Mini-Mental State Examination (MMSE). The total score ranges from 0 to 30, with higher scores indicating better cognitive function. Changes from baseline will be evaluated after the intervention and at follow-up. |
| Change in Go/No-Go Task Accuracy | Baseline, Week 8 | Inhibitory control will be assessed using accuracy on the Go/No-Go task. Accuracy will be expressed as the percentage of correct responses, with higher values indicating better performance. |
| Change in Go/No-Go Task Reaction Time | Baseline and Week 8 | Inhibitory control will be assessed using reaction time for correct responses on the Go/No-Go task. Reaction time will be recorded in milliseconds (ms), with shorter reaction times indicating faster task performance. |
| Change in n-back Task Accuracy | Baseline, Week 8 | Working memory performance will be assessed using accuracy on the n-back task. Accuracy will be expressed as the percentage of correct responses, with higher values indicating better performance. |
| Change in n-back Task Reaction Time | Baseline, Week 8 | Working memory performance will be assessed using reaction time for correct responses on the n-back task. Reaction time will be recorded in milliseconds (ms), with shorter reaction times indicating faster task performance. |
| Change in Digit Span Forward Score | Baseline and Week 8 | Attention and short-term memory will be assessed using the Digit Span Forward task. Performance will be recorded as the raw Digit Span Forward score, with higher scores indicating better performance. |
| Change in Digit Span Backward Score | Baseline and Week 8 | Working memory will be assessed using the Digit Span Backward task. Performance will be recorded as the raw Digit Span Backward score, with higher scores indicating better performance. |
| Change in Auditory Verbal Learning Test Trial 1 Recall | Baseline, Week 8, and Week 24 | Immediate verbal memory will be assessed using the number of words correctly recalled during Trial 1 (N1) of the Auditory Verbal Learning Test (AVLT). Higher numbers of correctly recalled words indicate better memory performance. |
| Change in Auditory Verbal Learning Test Trial 2 Recall | Baseline, Week 8, and Week 24 | Verbal learning performance will be assessed using the number of words correctly recalled during Trial 2 (N2) of the Auditory Verbal Learning Test (AVLT). Higher numbers of correctly recalled words indicate better performance. |
| Change in Auditory Verbal Learning Test Trial 3 Recall | Baseline, Week 8, and Week 24 | Verbal learning performance will be assessed using the number of words correctly recalled during Trial 3 (N3) of the Auditory Verbal Learning Test (AVLT). Higher numbers of correctly recalled words indicate better performance. |
| Change in Auditory Verbal Learning Test Trial 4 Recall | Baseline, Week 8, and Week 24 | Verbal learning performance will be assessed using the number of words correctly recalled during Trial 4 (N4) of the Auditory Verbal Learning Test (AVLT). Higher numbers of correctly recalled words indicate better performance. |
| Change in Auditory Verbal Learning Test Trial 5 Recall | Baseline, Week 8, and Week 24 | Verbal learning performance will be assessed using the number of words correctly recalled during Trial 5 (N5) of the Auditory Verbal Learning Test (AVLT). Higher numbers of correctly recalled words indicate better performance. |
| Change in Auditory Verbal Learning Test Recognition Correct Responses | Baseline, Week 8, and Week 24 | Recognition memory will be assessed using the number of correct recognition responses on the Auditory Verbal Learning Test (AVLT). A higher number of correct recognition responses indicates better recognition memory. |
| Change in Auditory Verbal Learning Test Recognition Errors | Baseline, Week 8, and Week 24 | Recognition memory errors will be assessed using the number of incorrect recognition responses on the Auditory Verbal Learning Test (AVLT). A lower number of recognition errors indicates better recognition memory performance. |
| Change in Face-Name Matching Task Accuracy | Baseline, Week 8, and Week 24 | Associative episodic memory will be assessed using accuracy on the face-name matching task. Accuracy will be expressed as the percentage of correct responses, with higher values indicating better performance. |
| Change in Face-Name Matching Task Reaction Time | Baseline, Week 8, and Week 24 | Associative episodic memory performance will be assessed using reaction time for correct responses on the face-name matching task. Reaction time will be recorded in milliseconds (ms), with shorter reaction times indicating faster task performance. |
| Change in Mnemonic Similarity Task Accuracy | Baseline, Week 8, and Week 24 | Episodic memory and mnemonic discrimination will be assessed using accuracy on the Mnemonic Similarity Task (MST). Accuracy will be expressed as the percentage of correct responses, with higher values indicating better performance. |
| Change in Mnemonic Similarity Task Reaction Time | Baseline, Week 8, and Week 24 | Performance on the Mnemonic Similarity Task (MST) will also be assessed using reaction time for correct responses. Reaction time will be recorded in milliseconds (ms), with shorter reaction times indicating faster task performance. |
| Change in Single-Task Timed Up and Go Completion Time | Baseline and Week 8 | Mobility under single-task conditions will be assessed using the Timed Up and Go (TUG) test. Completion time will be recorded in seconds, with shorter completion times indicating better mobility performance. |
| Change in Dual-Task Timed Up and Go Completion Time | Baseline and Week 8 | Cognitive-motor dual-task performance will be assessed using the Timed Up and Go (TUG) test performed concurrently with a cognitive task. Completion time will be recorded in seconds, with shorter completion times indicating better dual-task mobility performance. |
| Change in Timed Up and Go Dual-Task Cost | Baseline and Week 8 | Dual-task cost for Timed Up and Go completion time will be calculated as \[(dual-task completion time - single-task completion time) / single-task completion time\] × 100%. Higher positive values indicate greater deterioration in mobility performance under dual-task conditions. |
| Change in Single-Task Gait Speed | Baseline and Week 8 | Gait speed under single-task walking conditions will be recorded in meters per second (m/s). Higher gait speed indicates faster walking performance. |
| Change in Dual-Task Gait Speed | Baseline and Week 8 | Gait speed during cognitive-motor dual-task walking will be recorded in meters per second (m/s). Higher gait speed indicates faster walking performance during dual-tasking. |
| Change in Single-Task Gait Cadence | Baseline and Week 8 | Gait cadence under single-task walking conditions will be recorded as steps per minute (steps/min). Higher values indicate a greater number of steps performed per minute. |
| Change in Dual-Task Gait Cadence | Baseline and Week 8 | Gait cadence during cognitive-motor dual-task walking will be recorded as steps per minute (steps/min). Higher values indicate a greater number of steps performed per minute during dual-tasking. |
| Change in Single-Task Stride Length | Baseline and Week 8 | Stride length under single-task walking conditions will be recorded in meters (m). Greater values indicate longer stride length. |
| Change in Dual-Task Stride Length | Baseline and Week 8 | Stride length during cognitive-motor dual-task walking will be recorded in meters (m). Greater values indicate longer stride length during dual-tasking. |
| Change in Brain Structure and Function Assessed by Magnetic Resonance Imaging | Baseline, Week 8 | Changes in brain structure and function will be assessed using multimodal magnetic resonance imaging (MRI). MRI-derived structural and functional measures will be used to characterize intervention-related brain changes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Anxiety Rating Scale Score | Baseline, Week 8, and Week 24 | Anxiety symptoms will be assessed using the Hamilton Anxiety Rating Scale (HAM-A). The total score ranges from 0 to 56, with higher scores indicating greater anxiety symptom severity. |
| Change in 17-Item Hamilton Depression Rating Scale Score | Baseline, Week 8, and Week 24 | Depressive symptoms will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17). The total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. |
| Change in 15-Item Geriatric Depression Scale Score | Baseline, Week 8, and Week 24 | Depressive symptoms will also be assessed using the 15-item Geriatric Depression Scale (GDS-15). The total score ranges from 0 to 15, with higher scores indicating greater depressive symptom severity. |
| Change in Pittsburgh Sleep Quality Index Score | Baseline, Week 8, and Week 24 | Subjective sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI). The total score ranges from 0 to 21, with higher scores indicating poorer sleep quality. |
| Change in Epworth Sleepiness Scale Score | Baseline, Week 8, and Week 24 | Daytime sleepiness will be assessed using the Epworth Sleepiness Scale (ESS). The total score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness. |
| Change in REM Sleep Behavior Disorder Screening Questionnaire Score | Baseline, Week 8, and Week 24 | Symptoms related to REM sleep behavior disorder will be assessed using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ). The total score ranges from 0 to 13, with higher scores indicating more symptoms suggestive of REM sleep behavior disorder. |
| Change in Functional Activities Questionnaire Score | Baseline, Week 8, and Week 24 | Daily functional ability will be assessed using the Functional Activities Questionnaire (FAQ). The total score ranges from 0 to 30, with higher scores indicating greater impairment in instrumental activities of daily living. |
| Change in 12-Item Short Form Health Survey Physical Component Summary Score | Baseline, Week 8, and Week 24 | Physical health-related quality of life will be assessed using the Physical Component Summary (PCS) score of the 12-Item Short Form Health Survey (SF-12). The PCS is a norm-based summary score, with higher scores indicating better physical health-related quality of life. |
| Change in Go/No-Go Task-Evoked Oxygenated Hemoglobin Response Assessed by fNIRS | Baseline and Week 8 | Task-evoked cerebral hemodynamic response during the Go/No-Go task will be assessed using functional near-infrared spectroscopy (fNIRS). The primary fNIRS measure will be the task-related change in oxygenated hemoglobin (HbO) concentration in predefined cortical regions. |
| Change in n-back Task-Evoked Oxygenated Hemoglobin Response Assessed by fNIRS | Baseline and Week 8 | Task-evoked cerebral hemodynamic response during the n-back task will be assessed using functional near-infrared spectroscopy (fNIRS). The primary fNIRS measure will be the task-related change in oxygenated hemoglobin (HbO) concentration in predefined cortical regions. |
| Change in Mnemonic Similarity Task-Evoked Oxygenated Hemoglobin Response Assessed by fNIRS | Baseline and Week 8 | Task-evoked cerebral hemodynamic response during the Mnemonic Similarity Task (MST) will be assessed using functional near-infrared spectroscopy (fNIRS). The primary fNIRS measure will be the task-related change in oxygenated hemoglobin (HbO) concentration in predefined cortical regions. |
| Blinding Effectiveness | During the 8-week intervention period | Blinding effectiveness will be assessed by asking participants to indicate whether they believe they received active or sham transcranial temporal interference stimulation. Participants' treatment guesses will be used to evaluate the success of participant blinding. |
| Incidence and Severity of Adverse Events and Tolerability | Throughout the 8-week intervention period and at the Week 24 follow-up | Adverse events and tolerability will be assessed using structured questionnaires and participant reports. The occurrence, type, and severity of stimulation-related adverse events and discomfort will be recorded, including symptoms such as tingling, itching, headache, dizziness, or other reported adverse effects. |
Countries
China
Contacts
CONTACTZhen Xu
Outcome results
None listed