Brain Stimulation for Dementia and Memory Loss

Overseen By Aimee J Nelson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Must not be taking: Seizure medications

Disqualifiers: Pacemaker, Metal implants, Epilepsy, others

Compensation: Varies

Number of Visits: 15

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how brain stimulation, specifically Accelerated Intermittent Theta-burst Stimulation, might improve balance in people with dementia and memory loss. Researchers are testing whether targeting different brain areas can enhance balance abilities more effectively. Participants are divided into three groups: one receives active stimulation to a motor area, another to a decision-making area, and the third receives a placebo. Suitable candidates for this trial have been diagnosed with dementia or memory loss and can walk or stand with or without assistance. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance balance in those with dementia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking any prescription medications that increase the risk of seizures.

What prior data suggests that this brain stimulation technique is safe for improving balance in older adults?

Research has shown that accelerated intermittent theta-burst stimulation (iTBS) has been tested for safety in previous studies. Trials with older adults found iTBS to be safe and well-tolerated. Specifically, one study with older adults demonstrated that the treatment was feasible and acceptable, with no serious side effects reported.

Additionally, the FDA has approved iTBS for treating certain types of depression, indicating its general safety, though individual experiences may vary based on personal health conditions.

For those considering joining a clinical trial, this information suggests that the treatment is usually well-tolerated and safe. However, discussing any concerns with a healthcare professional is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of accelerated intermittent theta-burst stimulation (iTBS) for dementia and memory loss, which is a fresh approach compared to typical medications like cholinesterase inhibitors or memantine. iTBS is unique as it uses magnetic fields to stimulate specific brain regions, potentially enhancing memory and cognitive functions more directly and rapidly. The trial targets two different brain areas, M1 and DLPFC, to see which might yield the best results, adding a layer of precision not typically found in existing treatments. This method also incorporates balance training, aiming for a holistic improvement in brain and physical function, which is not a focus of conventional therapies.

What evidence suggests that this trial's treatments could be effective for dementia and memory loss?

This trial will compare different applications of accelerated intermittent theta-burst stimulation (iTBS) for managing memory loss and cognitive decline. Studies have shown that iTBS can improve memory and thinking skills in people with Alzheimer's disease. In this trial, one group will receive active iTBS targeting the brain area that controls movement, linked to better balance and a reduced risk of falls in older adults. Another group will receive active iTBS targeting a different brain area involved in decision-making and behavior, which research suggests can improve cognitive symptoms in Alzheimer's patients. Both methods have shown potential to enhance brain connections and overall cognitive recovery. These findings support the idea that iTBS might be a useful tool for managing memory loss and cognitive decline. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for older adults experiencing cognitive decline, such as dementia or Alzheimer's Disease, who are interested in a non-drug treatment aimed at improving balance and cognitive function. Participants should be able to perform daily activities with some degree of independence.

Inclusion Criteria

I am 50 years old or older.

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

I can walk or stand by myself or with help.

Exclusion Criteria

I don't have a pacemaker, metal implants (except titanium), untreated mental disorders, am not pregnant, have no history of seizures, and am not on medication that raises seizure risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive accelerated intermittent theta-burst stimulation (iTBS) to either M1 or DLPFC for 14 days, with three sessions per day separated by 15-minute intervals.

14 days

Daily visits for 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cognitive function and balance.

6 months

1-2 visits post-intervention

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Intermittent Theta-burst Stimulation

Trial Overview The study tests whether rTMS, a non-invasive brain stimulation technique, can improve balance by targeting either the motor cortex (M1) or the part of the brain involved in complex thinking tasks (DLPFC). The effectiveness is compared between active rTMS and placebo-like sham rTMS.

How Is the Trial Designed?

Group I: Active rTMS to M1 Active Control 1 Intervention

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 II: Active rTMS to DLPFC Active Control 1 Intervention

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 III: Placebo rTMS to M1 Placebo Group 1 Intervention

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).

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

Theta-burst stimulation appears to significantly reduce the severity of unilateral spatial neglect in stroke patients, based on a systematic review of nine studies involving 148 participants.

Despite the promising results, the evidence is limited and inconsistent due to variations in study protocols and terminology, making it difficult to draw definitive conclusions about its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of theta-burst stimulation on unilateral spatial neglect following stroke: a systematic review. Cotoi, A., Mirkowski, M., Iruthayarajah, J., et al.[2019]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

Intermittent theta burst stimulation (iTBS) significantly reduces amyloid-beta (Aβ) accumulation in the brains of APP/PS1 mice, indicating its potential to mitigate Alzheimer's disease-related pathologies.

The treatment not only lowers Aβ levels by inhibiting its production and enhancing its degradation but also reduces neuroinflammation, neuronal cell death, and synaptic loss, suggesting long-lasting protective effects on brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effects of intermittent theta burst stimulation on Alzheimer's disease-type pathologies in APP/PS1 mice. Huang, H., Zhu, Y., Liao, L., et al.[2023]

In a study involving 58 participants with mild to moderate Alzheimer's disease, intermittent theta burst stimulation (iTBS) was found to enhance gamma connectivity in the brain, which is linked to cognitive function.

Active iTBS treatment led to significant improvements in delayed recall on memory tasks, suggesting that this non-invasive stimulation technique could be a promising therapeutic approach for cognitive impairment in Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma connectivity predicts response to intermittent theta burst stimulation in Alzheimer's disease: a randomized controlled trial. Hoy, KE., Emonson, MRL., Bailey, NW., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X21008056

Accelerated intermittent theta-burst stimulation broadly ... Accelerate iTBS of the left DLPFC showed an effective and well-tolerated complementary treatment to improve symptoms and cognitive in AD patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12465570/

Effects of intermittent theta-burst stimulation on cognition ... Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in alleviating cognitive symptoms in Alzheimer's disease (AD) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10806514/

Effects of a periodic intermittent theta burst stimulation in ... Accelerated iTBS treatment applied to the left DLPFC in depressed patients results in a rapid volume increase in the left hippocampal ...

4. jnnp.bmj.com jnnp.bmj.com/content/95/11/1036

A phase I trial of accelerated intermittent theta burst rTMS for ... There is emerging evidence that suggests accelerated intermittent theta burst stimulation (iTBS) may benefit cognition in prodromal neurodegenerative disease, ...

5. bmcgeriatr.biomedcentral.com bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-024-05625-7

Effects of intermittent theta burst stimulation on cognitive and ... Navigated iTBS over the rDLPFC has the potential to improve global cognition, response inhibition ability, and certain aspects of swallowing function.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000932

Accelerated iTBS-Induced changes in resting-state ... Published results of our Phase I safety and feasibility trial of accelerated intermittent theta burst stimulation (a-iTBS) in mild cognitive impairment (MCI) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10952126

Accelerated Theta Burst Stimulation (aTBS) The conventional iTBS protocol is FDA-approved to treat otherwise treatment-resistant depression but the 6-week duration limits the applicability of this ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0361923023001600

The long-term effects of intermittent theta burst stimulation ... These data indicate that 1 month of iTBS treatment ameliorates pathologies in the brain of AD mice for at least 2 months.