Intermittent Theta-burst Stimulation for Mild Cognitive Impairment

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.

• Blood oxygenation level changes of the brain [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]
• Dual-task gait performance 1 (gait variability) [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]
• Dual-task gait performance 2 (stride length) [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]
• Dual-task gait performance 3 (walking distance) [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]
• Dual-task gait performance 4 (gait cadence) [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]
• Dual-task gait performance 5 (trunk stability) [Time frame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment]