Alzheimer Disease
Conditions
Keywords
Alzheimer Disease, Temporal Interference Stimulation
Brief summary
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.
Interventions
DEVICETemporal Interference Stimulation
Device: The non-invasive brain stimulator NervioX is used to administer Temporal Interference Stimulation (TIS). Stimulation Parameters: Frequencies: 2000 Hz and 2005 Hz (resulting in a 5 Hz theta rhythm envelope). Stimulation Intensity: 1.0-2.0 mA (peak current). Stimulation Target: Bilateral hippocampus Session Duration: 40 minutes per session. Treatment Course: 5 sessions per week, for 2 consecutive weeks, totaling 10 sessions.
DEVICESham Stimulation
Device: The same NervioX device is used. Stimulation Parameters: The device is programmed to deliver a real stimulation (1.0-2.0 mA) for the initial 30 seconds of the session to mimic the initial sensation experienced by the active group. Subsequently, the current is automatically reduced to 0 mA for the remainder of the 40-minute session. The device screen continues to display the stimulation as ongoing to maintain the blinding. The session frequency and total course (5 sessions/week for 2 weeks, 10 sessions total) are identical to the active intervention group.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 11) Score | Baseline, End of treatment (2 weeks) | The ADAS-Cog 11 is a rater-administered scale designed to assess the severity of cognitive dysfunction in Alzheimer's disease. The total score ranges from 0 to 70, with a lower score indicating better cognitive performance. The change from baseline to the end of treatment will be analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mini-Mental State Examination (MMSE) Score | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The MMSE is a brief 30-point questionnaire used to screen for cognitive impairment. The total score ranges from 0 to 30, with a higher score indicating better cognitive function. |
| Change in Montreal Cognitive Assessment (MoCA) Score | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The MoCA is a widely used screening assessment for detecting mild cognitive impairment. The total score ranges from 0 to 30, with a higher score indicating better cognitive function. |
| Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The CDR-SB is a numeric scale derived from the CDR global score, which provides a more detailed assessment of cognitive and functional performance across six domains. The total score ranges from 0 to 18, with a higher score indicating greater severity of dementia. |
| Change in Shape Trails Test (STT) - Part A Time | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The STT-A measures visual attention and processing speed. The time in seconds to complete the task is recorded, with a shorter time indicating better performance. This is a continuous measure without a predefined minimum/maximum range. |
| Change in Shape Trails Test (STT) - Part B Time | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The STT-B measures executive function, including task-switching and cognitive flexibility. The time in seconds to complete the task is recorded, with a shorter time indicating better performance. This is a continuous measure without a predefined minimum/maximum range. |
| Change in Digit Span Test (DST) Score | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | The DST is a component of cognitive tests that assesses attention and working memory. It includes forward span (attention) and backward span (working memory). The forward span typically ranges from 0 to 16, and the backward span from 0 to 14, with a higher number of correct sequences indicating better function. |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | From baseline through study completion (up to 16 weeks) | The number and severity of all AEs and SAEs will be collected and monitored throughout the study to evaluate the safety and tolerability of the intervention. |
| Change in Functional Connectivity measured by Resting-state Functional Magnetic Resonance Imaging (rs-fMRI) | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | Changes in brain network connectivity (e.g., within the default mode network and hippocampal connectivity) will be assessed using rs-fMRI. |
| Change in Theta Band Power measured by Electroencephalography (EEG) | Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks) | Changes in neural oscillatory activity will be assessed using high-density EEG. |
Countries
China
Outcome results
None listed