Temporal Interference Stimulation Combined With Tai Chi for Mild Cognitive Impairment

Effects of Transcranial Temporal Interference Stimulation Combined With Tai Chi Training on Cognitive Function, Dual-Task Performance, and Neuroimaging Mechanisms in Individuals With Mild Cognitive Impairment

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.

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.

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