Intermittent Theta-burst Stimulation for Mild Cognitive Impairment: a Randomized Double-Blinded Controlled Trial
- Conditions
- Mild Cognitive Impairment (MCI)
- Interventions
- Device: Intermittent Theta Burst Stimulation
- Registration Number
- NCT06608316
- Lead Sponsor
- The Hong Kong Polytechnic University
- Brief Summary
The objectives of this study are to:
1. Evaluating the Impact of iTBS on Cognitive and Physical Functions: We will investigate the efficacy of intermittent theta burst stimulation (iTBS) in patients with mild cognitive impairment (MCI), focusing on its effects on dual-task walking abilities, balance abilities, and cognitive function.
2. Comparing Clinical Efficacy Based on Stimulation Sites: We will compare the clinical efficacy of iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) versus bilateral DLPFC stimulation. This comparison aims to directly examine potential differences in therapeutic outcomes based on the site of stimulation.
3. Investigating Neurophysiological Mechanisms: We plan to elucidate the neurophysiological mechanisms underlying the improvements in cognitive functions and dual-task walking abilities in MCI patients facilitated by iTBS. This will be achieved using fNIRS neuroimaging of brain activity.
- Detailed Description
Mild cognitive impairment (MCI) is a syndrome characterized by cognitive decline that is greater than expected with normal aging; however, it is not severe enough to meet dementia criteria. Accordingly, MCI is considered a transitional state between normal aging and dementia, with a high risk of progression to Alzheimer's disease (AD). In MCI, memory and other cognitive domains such as executive function and visuospatial skills are typically affected. Furthermore, people with MCI have impaired dual-task walking function, decreased balance, and an increased risk of falls compared to cognitively normal older adults, thus affecting the ability to perform daily activities. Moreover, sleep disturbances, such as reduced efficiency and disruptions, are common in MCI, which exacerbates cognitive decline and accelerates the progression to dementia.
Non-invasive brain stimulation (NIBS) techniques have shown potential for enhancing both cognitive and functional outcomes in neuropsychiatric diseases. Transcranial magnetic stimulation (TMS) is the most common form of NIBS, which modulates cortical excitability and neuroplasticity by inducing electromagnetic pulses in targeted brain regions. TMS can be delivered in various forms based on frequency and intervals. Intermittent theta burst stimulation (iTBS) is a type of patterned TMS that mimics endogenous theta rhythms. It has shown cognitive benefits in healthy populations as well as those with AD, depression, and other conditions, but evidence regarding its efficacy in MCI is limited.
While interventions like dual-task training and non-invasive brain stimulation (e.g., tDCS) have shown promise in mitigating dual-task coordination impairments, research specifically focusing on the impact of iTBS on dual-task walking abilities in MCI patients remains scarce. Further research is needed to explore the potential of iTBS to improve dual-task walking ability, balance, and fall prevention in MCI populations.
Although the dorsolateral prefrontal cortex (DLPFC) is often targeted with NIBS due to its role in executive functions, comparisons of bilateral versus unilateral left DLPFC stimulation have not been conducted in MCI. Overall, there is a lack of empirical evidence supporting the use of iTBS protocols to improve cognition and functional activities in MCI. Elucidating the neurophysiological mechanisms underlying NIBS techniques like iTBS remains imperative.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 66
- The inclusion criteria of MCI included: (1) aged≥65 years; (2) patient-reported subjective cognitive decline and the total score of the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) was between 19 and 25; (3) intact daily functioning in ADL scales and being independent in daily living, and ability to walk at least for 1 minute independently without an assistive device; (4) no serious visual or hearing impairment and can complete relevant assessment and testing; and (5) signed informed consent of patients and their families for iTBS treatment.
- The inclusion and exclusion criteria of healthy control subject: Healthy control subjects (HC) were matched to the age and gender with the enrolled MCI patients and had no comorbid neurological, psychiatric, or significant medical conditions, were enrolled. They underwent HK-MoCA (scores ≥ 26), which excluded the objective evidence of cognitive and functional impairment. The other exclusion criteria are the same as for the MCI population.
- The exclusion criteria of MCI included: (1) identified with contraindications in the rTMS screening questionnaire; (2) cognitive dysfunction due to craniocerebral trauma or neurological diseases; (3) presence of severe physical illnesses such as speech disorders or unstable cardiac arrhythmias; (4) currently in a critical condition such as fever, infection, or organ failure; (5) significant damage to the left frontal lobe cortex; (6) currently taking antidepressants or psychostimulants; (7) unstable vital signs or organ failure; (8) neuropsychiatric comorbidity or affective disorder that could affect the test results; (9) patients with dementia.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Left DLPFC stimulation group Intermittent Theta Burst Stimulation 80% resting motor threshold (RMT) iTBS stimulated the left DLPFC 4 sessions per day at 15 min intervals (3min per session), 3 days per week for 3 weeks. Sham stimulation of the right DLPFC will be performed. Bilateral DLPFC stimulation group Intermittent Theta Burst Stimulation 80% RMT iTBS stimulated the bilateral DLPFC 4 sessions per day at 15 min intervals (2 sessions on the left, 2 sessions on the right, 3 min per session), 3 days per week for 3 weeks. Sham stimulation group Intermittent Theta Burst Stimulation Sham coil stimulates the left and right DLPFC.
- Primary Outcome Measures
Name Time Method Dual-task cost in cognition (Reaction time) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Reaction time will be measured during dual-task conditions
Dual-task cost in gait (gait speed) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Gait speed under dual-task condition will be recorded
Dual-task cost in cognition (Accuracy) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Accuracy will be measured during dual-task conditions
- Secondary Outcome Measures
Name Time Method Dual-task gait performance 1 (gait variability) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Gait variability will be measured during dual-task walking
Dual-task gait performance 5 (trunk stability) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Trunk stability will be measured during dual-task walking
Dual-task gait performance 3 (walking distance) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Walking distance will be measured during dual-task walking
Blood oxygenation level changes of the brain before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Blood oxygenation level changes will be measured using Functional Near-Infrared Spectroscopy during dual-task conditions
Dual-task gait performance 2 (stride length) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Stride length will be measured during dual-task walking
Dual-task gait performance 4 (gait cadence) before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment Gait cadence will be measured during dual-task walking
Trial Locations
- Locations (1)
The Hong Kong Polytechnic University
🇭🇰Hong Kong, Hong Kong