Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

A Randomized, Double-Blind, Controlled Trial to Evaluate the Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

This study aims to investigate the efficacy and safety of a novel non-invasive brain stimulation technique-Temporal Interference Stimulation (TIS)-in patients with early-stage Alzheimer's disease. A total of 40 participants will be randomly assigned to either the TIS group or the sham stimulation group. The intervention will last for 2 weeks, with cognitive and safety assessments at baseline, post-treatment, and 12 weeks after treatment.

Inclusion Criteria：

1. According to the 2024 NIA-AA Revised Criteria , defined as positivity for at least one Core 1 biomarker:

   • Positive plasma p-tau217 test (positivity defined by clinically validated diagnostic cutoffs provided by the assay manufacturer); or
   • Positive amyloid PET scan; or
   • Abnormal cerebrospinal fluid (CSF) ratios, including p-tau181/Aβ42, t-tau/Aβ42, or Aβ42/40.

   *Reference: Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169.*

2. Age between 50 and 75 years, inclusive.

3. Minimum of 6 years of formal education.

4. Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.

5. MMSE≥21.

6. Stable dosage of cognitive-enhancing medications (e.g., cholinesterase inhibitors and/or memantine) for at least 6 weeks prior to screening.

Exclusion Criteria:

1. Current or past history of significant neurological disorders other than AD (e.g., epilepsy, stroke, multiple sclerosis), intracranial lesions, neurosurgery, or significant head trauma.
2. Current use of medications that may substantially impair cognitive function (e.g., anticonvulsants, antipsychotics, benzodiazepines).
3. Any contraindication for MRI or the stimulation device (e.g., metallic implants, pacemakers, severe claustrophobia).
4. Significant structural brain abnormalities on MRI (e.g., hydrocephalus, stroke, or severe white matter lesions [Fazekas score ≥ 3]).
5. Diagnosis of major depression or other active, uncontrolled psychiatric disorders.
6. Any severe or unstable medical condition that, in the investigator's judgment, could compromise participant safety or study validity (e.g., cardiovascular, renal, hepatic, respiratory, active cancer), or a history of alcohol/substance dependence.