Accelerated Intermittent Theta-burst Stimulation to Modify Cognitive Function and Balance in Dementia and Memory Loss

NCT ID: NCT06445894

Last Updated: 2024-06-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2025-09-01

Brief Summary

The process of aging is accompanied by normal deterioration of body systems, leading to a decline in various functional domains including cognitive, visual, vestibular, somatosensory, and motor function. With this functional decline, there is an increasing burden of care due to the rise of injury, direct and indirect healthcare costs, and the loss of independence in performing daily activities. Notably, falls in the older population represents one of the greatest costs incurred by Canadians annually.

The study investigates whether rTMS delivered to M1 will lead to greater improvement in balance compared to rTMS delivered to DLPFC. Determining this answer will allow greater success in TMS target refinement. Given the profound burden that geriatric medicine has on the Canadian healthcare system, understanding the link between balance and cognition can significantly impact the approach to management of this population.

Detailed Description

Approximately 20-30% of Canadian adults >65 years old experience falls each year, and this rate drastically increases for those >85 years of age [2]. With the aging population, the number of annual reported falls has increased by 47% from 2008 to 2020 [3]. Individuals with cognitive impairment exhibit an 8x higher risk of falls compared to those without [4]. Balance is a key risk factor for falls [5-7], and there is evidence suggesting that balance control is a marker of cognitive decline [8]. For example, cognitive function is significantly correlated with postural control [9] and postural sway [10]. In Parkinson's disease, balance has been linked to greater executive dysfunction and slower processing speed [11].

Synaptic plasticity induced via neuromodulatory techniques can lead to improvements in motor and cognitive function. One such technique is Transcranial magnetic stimulation (TMS), a non-invasive form of neuromodulation. To induce synaptic plasticity, magnetic stimuli are delivered via TMS in theta-burst patterns. This includes continuous theta burst stimulation (cTBS) that induces long term depression (LTD)-like changes in neuronal excitability and intermittent theta burst stimulation (iTBS) that induces long term potentiation (LTP)-like changes in neuronal excitability [12]. Previous literature suggests that iTBS may be an effective tool for modulating cognition and motor function.

Wu et al. (2022) found an improvement in memory function of Alzheimer disease patients following a 14-day course of iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) [13]. Trung et al. (2019) showed that 3 days of iTBS delivered to the DLPFC led to cognitive improvements in a sample of Parkinson's disease patients with mild cognitive impairment (MCI) [14]. Regarding balance, iTBS has been shown to be an effective intervention for balance recovery when delivered to the cerebellum [16,17] or the primary motor cortex (M1) [16]. Improvements in gait performance have also been seen following other patterns of stimulation including repetitive TMS (rTMS) in the post-stroke population [18-20]. These improvements in cognition and balance following iTBS may be linked to plastic changes in neuronal structure, as seen in animal models [21].

Accelerated intermittent theta-burst stimulation (iTBS) encompass multiple sessions of iTBS administered within a singular day over the course of several days, consequently diminishing the duration of the treatment regimen. aiTBS has been shown to be a tolerable and safe form of non-invasive brain stimulation with rapid antidepressant efficacy and anti-suicidal effects in patients with major depressive disorder [22-27]. Previous studies have demonstrated aiTBS paradigm which consisted of iTBS delivered 3 times per day separated by 15 min intervals, over the course of 14 days, resulted in an improvement in memory function in individuals with Alzheimer disease [13, 27].

For this study question we have chosen two different stimulation sites. DLFPC is known for its contributions to learning and memory. Individuals with dementia typically receive rTMS stimulation to DLPFC to explore whether cognitive function can be improved (Wu et al., 2020). It has been seen that individuals with dementia suffer from a greater number of falls, it is unclear whether rTMS to DLPFC will improve balance performance and risk of falls better than rTMS delivered to M1, a typical site of stimulation for balance related studies. iTBS has been shown to be an effective intervention for balance recovery when delivered to the primary motor cortex (M1) (Liao et al., 2024). Improvements in gait performance have also been seen following other patterns of stimulation including repetitive TMS (rTMS) in the post-stroke population when delivered to M1 (Wang et al., 2012; Wang et al., 2019; Rastgoo et al., 2016). These improvements in cognition and balance following iTBS may be linked to plastic changes in neuronal structure, as seen in animal models (Tsang et al., 2021).

We there ask the study question whether rTMS delivered to M1 will lead to greater improvement in balance compared to rTMS delivered to DLPFC. Determining this answer will allow greater success in TMS target refinement. Given the profound burden that geriatric medicine has on the Canadian healthcare system, understanding the link between balance and cognition can significantly impact the approach to management of this population

Conditions

Dementia Alzheimers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo rTMS to M1

sham iTBS will be delivered using a Magstim Rapid 2 stimulator (Magstim, Whitland, UK) guided with neuronavigation (Brainsight, Rogue Research, Montreal, QC, Canada) to target M1. Participants will receive 14 days of placebo stimulation. Following sham iTBS individuals will participate in 10 minutes of balance training performed on balance board (BTracks https://balancetrackingsystems.com).

Group Type: PLACEBO_COMPARATOR

Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: DEVICE

A sham coil will be utilized for the sham rTMS condition. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active. The location and all other parameters of Sham rTMS will be identical to Active rTMS.

Active rTMS to M1

iTBS will be delivered using a Magstim Rapid 2 stimulator (Magstim, Whitland, UK) guided with neuronavigation (Brainsight, Rogue Research, Montreal, QC, Canada) to target M1. Participants will receive 14 days of stimulation. During each treatment day, three iTBS sessions separated by 15-minute intervals will be delivered. Each iTBS session consists of 600 stimuli delivered in 50 Hz bursts of 3 pulses at 70% of the resting motor threshold. In total, individuals will receive 1800 stimuli delivered each day as performed elsewhere . Following iTBS individuals will participate in 10 minutes of balance training performed on balance board (BTracks https://balancetrackingsystems.com).

Group Type: ACTIVE_COMPARATOR

Active Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

rTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The first dorsal interossesous (FDI) muscle of the left motor cortex will be targeted using neuronavigation software.

Active rTMS to DLPFC

iTBS will be delivered using a Magstim Rapid 2 stimulator (Magstim, Whitland, UK) guided with neuronavigation (Brainsight, Rogue Research, Montreal, QC, Canada) to target DLPFC. Participants will receive 14 days of stimulation. During each treatment day, three iTBS sessions separated by 15-minute intervals will be delivered \[13,22\]. Each iTBS session consists of 600 stimuli delivered in 50 Hz bursts of 3 pulses at 70% of the resting motor threshold. In total, individuals will receive 1800 stimuli delivered each day as performed elsewhere \[13,23,27\]. Following iTBS individuals will participate in 10 minutes of balance training performed on balance board (BTracks https://balancetrackingsystems.com).

Group Type: ACTIVE_COMPARATOR

Active Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

rTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The first dorsal interossesous (FDI) muscle of the left motor cortex will be targeted using neuronavigation software.

Interventions

Active Repetitive Transcranial Magnetic Stimulation

rTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The first dorsal interossesous (FDI) muscle of the left motor cortex will be targeted using neuronavigation software.

Intervention Type: DEVICE

Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

A sham coil will be utilized for the sham rTMS condition. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active. The location and all other parameters of Sham rTMS will be identical to Active rTMS.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Individuals must be diagnosed with Dementia and/or memory loss by a clinician.

2. Individuals must exhibit adequate oral communication skills and cognitive function sufficient to obtain a score ranging between 10-27 on the Mini-Mental State Exam (Wu et al., 2022).

3. Instructions will be delivered in English; therefore participants must demonstrate an understanding of instruction provided in English or have a caregiver present who can translate and be presented during all study sessions.

4. Individuals must be able to walk or stand with or without personnel or assistive devices.

5. Individuals must be greater than or equal to 50 years of age.

Exclusion Criteria

• 1. Contraindications to rTMS; presence of a pacemaker, metal/electrical/magnetic implants not including titanium, known history of untreated or uncontrolled psychological disorders, pregnancy, history of seizure or diagnoses of epilepsy, are taking any prescription medications that increase the risk of seizure.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Aimee Nelson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

McMaster Unviersity

Hamilton, Ontario, Canada

Countries

Canada

Central Contacts

Aimee J Nelson, PhD

Role: CONTACT

nelsonaj@mcmaster.ca

9055259140 ext. 28053

Other Identifiers

17300

Identifier Type: -

Identifier Source: org_study_id