Effects of Transcranial Temporal Interference Stimulation on Cognitive Function in Mild Cognitive Impairment

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.

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.

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