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Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that is increasingly used for a growing number of research and clinical applications.Typically, this transient magnetic field is focally applied with a figure-of-eight coil that is carefully placed on the surface of the scalp over a targeted stimulation site. Patterned repetitive TMS (rTMS), such as theta burst stimulation (TBS) can produce long-lasting effects on neural activity and behavior beyond the stimulation period (Chou et al., 2015a; Fitzgerald et al., 2006). In general, high frequency (> 5 Hz) rTMS and its newer version, intermittent theta burst stimulation (iTBS), facilitate cortical excitability, whereas low frequency (about 1 Hz) rTMS and continuous theta burst stimulation contribute to opposite effects (Pascual-Leone et al., 2000; Huang et al., 2005; Wassermann and Zimmermann, 2012).Careful manipulation of the parameters comprising these patterned rTMS pulse trains can induce neuroplastic changes that resemble either long-term potentiation (LTP) or depression (Chen et al., 1997; Pascual-Leone et al., 1994). Early studies targeting the motor cortex helped elucidate which rTMS parameters promote particular responses and their neurophysiological underpinnings (Klomjai et al., 2015).
In recent years, rTMS has been closely investigated to evaluate its potential to modulate cognitive functions in Alzheimer'sdisease (AD) and mild cognitive impairment (MCI). As compared to conventional excitatory rTMS protocols, iTBS leads to comparable effects with similar number of pulses but considerable shorter duration and lower intensity of stimulation (Bakker et al., 2015; Rossi, Hallett, Rossini, Pascual-Leone, & Safety, 2009). Recent literature also suggest that TBS has lower rates of reported adverse event (AE) compared to rTMS (Najib & Horvath, 2014). Therefore, iTBS is assumed to modulate cognitive function in people with cognitive impairments.
Visit 1: Informed Consent, Brain MRI/Neuropsychological Battery
Visit 2-11: (up to a week after visit 1) iTBS - or Sham-Treatment (10 sessions, 80% Resting Motor Threshold, 2s stimulation 8s inter-stimulus interval per train, 20 trains per block, 3 blocks per session with a 5-min break, 1 session per day)
Visit 12: (1 day or same day after visit 11) Functional Brain MRI/Neuropsychological Battery
Visit 13: (4 weeks after visit 11) Functional Brain MRI/Neuropsychological Battery
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| active iTBS | Experimental | The patient is treated with iTBS stimulation according to protocol with an active coil. |
|
| Sham iTBS | Sham Comparator | The patient is treated with Sham-iTBS stimulation according to protocol with an inactive coil. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| intermittent theta burst stimulation | Device | active or Sham iTBS will be given to the AD/MCI patient |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes from baseline in scores of any tests of the Neuropsychological Battery | WAIS-IV short-form, Word Sequence Learning Test, Benton Visual Retention Test, Color Trial Tests, 3-D Dimensional Constructional Test, Visual Confrontation Naming, Semantic Verbal Fluency Test, Stroop Color-Word Test | Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS) |
| Measure | Description | Time Frame |
|---|---|---|
| Brain MRI | Change in white matter and brain activities at resting state at baseline compared to after iTBS stimulation | Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yi-Chun Kuan, MD | Taipei Medical University Shuang Ho Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shuang Ho Hospital | New Taipei City | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41013466 | Derived | Yang CC, Huang KY, Hsu JL, Hu CJ, Lu YH, Kuan YC. Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial. J Neuroeng Rehabil. 2025 Sep 26;22(1):195. doi: 10.1186/s12984-025-01738-1. |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
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The participant and principal investigator do not know what treatment is applied. The outcomes assessor will also be blinded. Only the co-PI who perform the TMS will know the stimulation condition.
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |