Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment

A Randomized, Sham-Controlled Trial of Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment

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.

Inclusion Criteria:

• meets the criteria for probable AD and MCI due to AD as defined by the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines;
• Positive amyloid biomarker (amyloid PET or CSF tTau/Aβ 42);
• Positive tau biomarker (tau-PET or CSF pTau181);
• AD-related standard treatments (acetyl cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists) taken at a stable dose for at least 12 weeks prior to baseline.
• meets the criteria for probable bvFTD as defined by the revised diagnostic criteria for the behavioural variant of frontotemporal dementia (2011), or PPA as defined by the Classification of primary progressive aphasia and its variants (2011);
• Optional genetic confirmation of FTD-related pathogenic mutations (if available).
• Aged between 45 and 85 years, inclusive; no gender limitation.
• Right-handed.
• Education level ≥ 3 years.
• Mini-Mental State Examination (MMSE) score ≥ 11.
• Clinical Dementia Rating (CDR) score of 1 or 2.
• with a reliable caregiver
• Able to cooperate with cognitive assessments and cognitive training procedures.
• Full understanding of the study, voluntary participation, and provision of written informed consent approved by the Ethics Committee.

Exclusion Criteria:

• Diagnosis of other types of dementia or major neurological disorders (e.g., stroke, epilepsy, Lewy body dementia, vascular dementia, Parkinson's disease dementia, Huntington's disease).
• Major psychiatric disorders such as severe depression or anxiety.
• Severe systemic or organ dysfunction (e.g., heart failure III-IV, liver cirrhosis, renal failure).
• Use of medications that significantly affect cognition (e.g., anticholinergics, sedatives), unless approved by the physician.
• Presence of metal implants incompatible with MRI or TIS (e.g., pacemakers, deep brain stimulators).
• Skull defects or cranial abnormalities.
• Inability to tolerate EEG or head stabilization.
• Severe visual or hearing impairment preventing task performance.
• History of alcohol or drug abuse.
• Participation in another clinical trial within the past 3 months.
• Current or recent treatment with anti-amyloid monoclonal antibodies (e.g., lecanemab, donanemab).