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

36 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Accelerated Intermittent Theta-burst Stimulation for dementia and memory loss?

Research shows that intermittent theta burst stimulation (iTBS) can improve memory recall in Alzheimer's patients by enhancing brain connectivity. Additionally, studies in mice suggest that iTBS may reduce harmful brain changes associated with Alzheimer's, potentially improving cognitive function. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Theta burst stimulation (TBS) is generally considered safe, with most side effects being mild and occurring in about 5% of people. However, there is a small risk of seizures, so it should be used carefully, especially since it's a newer treatment. ^{1 4 6 7 8}

How does the treatment Accelerated Intermittent Theta-burst Stimulation differ from other treatments for dementia and memory loss?

Accelerated Intermittent Theta-burst Stimulation (iTBS) is unique because it uses magnetic pulses to stimulate specific brain areas, potentially improving memory and reducing Alzheimer's disease symptoms by enhancing brain connectivity and reducing harmful proteins. Unlike traditional treatments, iTBS may have lasting effects even after the treatment period ends. ^{1 2 3 4 8}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gamma connectivity predicts response to intermittent theta burst stimulation in Alzheimer's disease: a randomized controlled trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The effect of theta-burst stimulation on unilateral spatial neglect following stroke: a systematic review. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Delirium: A Double-blind, Randomized, Sham-controlled, Pilot Study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The long-term effects of intermittent theta burst stimulation on Alzheimer's disease-type pathologies in APP/PS1 mice. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Long-term effects of continuous theta-burst stimulation in visuospatial neglect. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Theta-burst stimulation as a therapeutic tool in neurological pathology: a systematic review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Theta Burst Stimulation Enhances Connectivity of the Dorsal Attention Network in Young Healthy Subjects: An Exploratory Study. [2018]