Clinical trial NCT06608316: Intermittent Theta-burst Stimulation for Mild Cognitive Impairment
Official title: Optimizing Intermittent Theta-burst Stimulation for Enhancing Dual-Task Walking, Cognitive, and Physical Function in Mild Cognitive Impairment: a Randomized Double-Blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment (MCI)
Keywords: Intermittent Theta Burst Stimulation (iTBS)
Dorsolateral Prefrontal Cortex (DLPFC)
dual task walking
cognitive function
Lead sponsor: The Hong Kong Polytechnic University
Sponsor class: OTHER
First posted: 2024-09-23
Enrollment: 66
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment: After stratification according to gender and age, the participants will be randomly allocated to one of three groups: (1) Left DLPFC stimulation group, (2) Bilateral DLPFC stimulation group, and (3) Sham stimulation group, using a 1:1:1 allocation ratio.
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to:

1. Evaluating the Impact of iTBS on Cognitive and Physical Functions: The investigators 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: The investigators 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: The investigators 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.

Eligibility criteria: Inclusion Criteria:

* Aged≥65 years;
* 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;
* 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;
* No serious visual or hearing impairment and can complete relevant assessment and testing;
* Signed informed consent of patients and their families for iTBS treatment.

Exclusion Criteria:

* Identified with contraindications in the rTMS screening questionnaire;
* Cognitive dysfunction due to craniocerebral trauma or neurological diseases;
* Presence of severe physical illnesses such as speech disorders or unstable cardiac arrhythmias;
* Currently in a critical condition such as fever, infection, or organ failure;
* Significant damage to the left frontal lobe cortex;
* Currently taking antidepressants or psychostimulants;
* Unstable vital signs or organ failure;
* Neuropsychiatric comorbidity or affective disorder that could affect the test results;
* Patients with dementia.

Primary outcomes:
measure: Dual-task cost in cognition (Reaction time)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task cost in gait (gait speed)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task cost in cognition (Accuracy)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
Secondary outcomes:
measure: Blood oxygenation level changes of the brain
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task gait performance 1 (gait variability)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task gait performance 2 (stride length)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task gait performance 3 (walking distance)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task gait performance 4 (gait cadence)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Dual-task gait performance 5 (trunk stability)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
Other outcomes:
measure: Hong Kong Montreal Cognitive Assessment (HK-MoCA)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: N-back test
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Modified-Wisconsin Card Sorting Test
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Hong Kong List Learning Test (HKLLT)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Brief assessment of prospective memory (short form).
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Timed Up and Go test
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Single Leg Stance test
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Pittsburgh Sleep Quality Index
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Depression, Anxiety, and Stress Scale (DASS-21)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Physical Activity Scale for the Elderly (PASE)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Fall incidence
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
measure: Hong Kong Lawton Instrumental Activities of Daily Living Scale (HKLIADL)
timeFrame: before the initiation of treatment, after 3 weeks of treatment, 4 weeks after termination of the treatment
Locations:
city: Hong Kong
country: Hong Kong
facility: The Hong Kong Polytechnic University
city: Hong Kong
country: Hong Kong
facility: The Hong Kong Polytechnic University
Study officials:
References: