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

Prior treatment

• Current use of medications that may substantially impair cognitive function (e.g., anticonvulsants, antipsychotics, benzodiazepines).
• Any contraindication for MRI or the stimulation device (e.g., metallic implants, pacemakers, severe claustrophobia).

Other illness

• Current or past history of significant neurological disorders other than AD (e.g., epilepsy, stroke, multiple sclerosis), intracranial lesions, neurosurgery, or significant head trauma.
• Significant structural brain abnormalities on MRI (e.g., hydrocephalus, stroke, or severe white matter lesions \[Fazekas score ≥ 3\]).
• Diagnosis of major depression or other active, uncontrolled psychiatric disorders.
• 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.

• 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.\*
• Age between 50 and 75 years, inclusive.
• Minimum of 6 years of formal education.
• Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.
• MMSE≥21.
• Stable dosage of cognitive-enhancing medications (e.g., cholinesterase inhibitors and/or memantine) for at least 6 weeks prior to screening.