Effects of Transcranial Temporal Interference Stimulation on Cognitive Function in Mild Cognitive Impairment (TIS-MCI)

The Effects of Transcranial Temporal Interferential Electrical Stimulation on Cognitive Function, Dual-Task Performance and Neuroplasticity in Individuals With Mild Cognitive Impairment

To explore the effects of transcranial temporal interference stimulation (tTIS) on cognitive function and dual-task walking performance, as well as its underlying neuroimaging mechanisms, in individuals with mild cognitive impairment.

Study Overview

• Status: Enrolling by invitation
• Conditions: Mild Cognitive Impairment (MCI)
• Intervention / Treatment: Device: Active Temporal Interference Stimulation (TIS); Device: Placebo / Sham TIS

Detailed Description

This is a randomized, double-blind, sham-controlled, crossover trial. Participants aged 60-80 years with mild cognitive impairment (MoCA < 26, CDR = 0.5) will receive a single 20-minute session of individualized 5 Hz transcranial temporal interference stimulation (tTIS) targeting the left hippocampus (2 mA, 2000/2005 Hz carriers) and a sham session in random order, with a 7-day washout period. The primary outcomes are change in MoCA score, dual-task gait/balance cost, and working memory performance. Secondary outcomes include change in brain function and brain structure. The study aims to enroll 40 participants. Safety and tolerability will be assessed via structured questionnaires.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200438
      • Shanghai University of Sport

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active TIS followed by Placebo TIS; Participants first receive single-session active TIS targeting the hippocampus for approx. 20 minutes. Following a washout period, they receive placebo (sham) TIS.	Device: Active Temporal Interference Stimulation (TIS); 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.; Device: Placebo / Sham TIS; Sham 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.
Experimental: Placebo TIS followed by Active TIS; Participants first receive single-session placebo (sham) TIS for approx. 20 minutes. Following a washout period, they receive active TIS targeting the hippocampus.	Device: Active Temporal Interference Stimulation (TIS); 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.; Device: Placebo / Sham TIS; Sham 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Montreal Cognitive Assessment (MoCA) Score	Baseline and immediately after intervention
Change in Gait-Related and Balance-Related Dual-Task Cost	Baseline and immediately after intervention
Change in Working Memory Performance	Baseline and immediately after intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Brain function	Baseline and immediately after intervention
Chang in Brain structure	Baseline and immediately after intervention

Collaborators and Investigators

• Sponsor: Shanghai University of Sport
• Collaborators: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 4, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 102772025RT208; ChiCTR2600119709 (Other Identifier: Chinese Clinical Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for primary and secondary outcome measures will be made available upon reasonable request to the corresponding author after publication of the main results.
• IPD Sharing Time Frame: Beginning 6 months after publication of the main results.
• IPD Sharing Access Criteria: Data will be made available upon reasonable request to the corresponding author. Data will be shared with researchers who submit a methodologically sound research proposal and intend to use the data for non-commercial purposes. Applicants must sign a data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No