dTMS + Cognitive Training for Mild Cognitive Impairment

Overseen By Linda Mah

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rotman Research Institute at Baycrest

Must not be taking: Benzodiazepines, Hypnotics

Disqualifiers: Depression, Psychotic disorders, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants be stable on their medications for 2 months and not change them during the study. If you are taking medications, you should not expect to stop them, but they must remain unchanged throughout the trial.

What data supports the effectiveness of the treatment dTMS + Cognitive Training for Mild Cognitive Impairment?

Research shows that repetitive transcranial magnetic stimulation (rTMS), a technique similar to dTMS, can improve cognitive function in people with mild cognitive impairment (MCI), especially when used frequently and on multiple brain areas. Additionally, cognitive training has shown some benefits in improving cognitive and psychosocial functions in MCI. ^{1 2 3 4 5}

Is the combination of dTMS and cognitive training safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS), which is similar to dTMS, combined with cognitive training is generally safe for people with Alzheimer's disease and mild cognitive impairment. Some studies report few adverse reactions, indicating it is well-tolerated by most participants. ^{2 6 7 8 9}

How does the treatment dTMS + Cognitive Training for Mild Cognitive Impairment differ from other treatments?

The treatment combines deep transcranial magnetic stimulation (dTMS), which uses magnetic fields to stimulate brain activity, with cognitive training exercises that enhance brain plasticity (the brain's ability to change and adapt). This dual approach is unique because it targets both brain stimulation and cognitive enhancement, potentially offering more comprehensive benefits than treatments focusing on just one of these aspects. ^{1 2 3 10 11}

What is the purpose of this trial?

Deep transcranial magnetic stimulation (dTMS) is a brain stimulation technique that involves generating a brief magnetic field in a coil that is placed on the scalp. The magnetic field passes through the skull and induces a weak electrical current in the brain that briefly activates neural circuits at the stimulation site. The Brainsway dTMS H7-Coil is able to target an area of the brain that has been shown in studies to be linked to greater resilience to cognitive decline. In this study, the investigators will combine dTMS with cognitive training in older adults with subjective cognitive decline (SCD) and examine the effect of this treatment on memory, other cognitive abilities, and mood. In addition, the investigators will examine the combined effects of dTMS and cognitive training on brain activity as measured using electroencephalography (EEG). Approximately 30 older adults from ages 55 to 70 with SCD and a positive family history of Alzheimer's disease will be enrolled in this study.

Research Team

Linda Mah

Principal Investigator

Baycrest Rotman Research Institute

Eligibility Criteria

This trial is for adults aged 55 to 70 with subjective cognitive decline and a family history of Alzheimer's. Participants must score at least 26 on the MoCA test, be stable on medications, and have someone to report on their condition. Exclusions include significant heart conditions, brain lesions or metal implants in the head (excluding dental), certain psychiatric disorders, substance abuse, pregnancy, untreated thyroid issues, hearing loss requiring aids, epilepsy or family history of it.

Inclusion Criteria

Have a satisfactory safety screening questionnaire for TMS

Are willing to provide informed consent

Have an informant/study partner who is able to complete study questionnaires regarding the participant

Exclusion Criteria

You have a pacemaker for your heart.

You have depression now or in the past, or have had certain mental health conditions like bipolar disorder or post-traumatic stress disorder.

Are a pregnant or breast-feeding woman

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 sessions of dTMS or sham intervention followed by cognitive training

4 weeks

20 sessions (in-person)

Follow-up

Participants are monitored for changes in cognitive and mood assessments after treatment

1 month

Treatment Details

Interventions

• Cognitive Training
• Deep Transcranial Magnetic Stimulation (dTMS)

Trial Overview The study tests if combining Deep Transcranial Magnetic Stimulation (dTMS) using Brainsway H7-Coil with cognitive training improves memory and cognition in those experiencing early signs of cognitive decline. The effects will also be measured through EEG brain activity monitoring.

Participant Groups

Group I: 20 sessions of dTMS and Cognitive Training Experimental Treatment 2 Interventions

Participants will receive dTMS followed by computerized cognitive training. dTMS: The motor threshold (MT) will be measured by delivering single stimulations to the motor cortex with gradually increased intensity. After defining the MT, the coil will be positioned anterior to the hot spot using the ruler on the participant's cap, and a dTMS session will be performed with the dosing of the stimulus intensity titrated slowly to approximately 120% of the motor threshold. On Day 1 of the treatment, stimulation will be delivered at an intensity ranging from 80% to 100% of the participant's MT depending on their initial tolerance to the stimulation. Stimulation intensity will then be slowly titrated by sequentially increasing the intensity by 10% over the remaining days of the first week until a maximum intensity of 120% of MT is achieved depending on the tolerability of the patient. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.

Group II: 20 sessions of sham/control stimulation and Cognitive Training Placebo Group 2 Interventions

Participants will receive sham intervention followed by computerized cognitive training. The sham intervention consists of treatment with similar technical parameters which induce scalp sensations but do not penetrate into the brain. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.

Who Is Running the Clinical Trial?

Rotman Research Institute at Baycrest

Lead Sponsor

Trials

11

Recruited

460+

Brainsway

Industry Sponsor

Trials

38

Recruited

2,800+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

Findings from Research

High-frequency repetitive transcranial magnetic stimulation (HFrTMS) showed significant short-term improvements in general cognition for patients with Alzheimer's disease (AD), while anodal transcranial direct current stimulation (atDCS) also had positive effects, but to a lesser extent.

Cognitive training during rTMS or tDCS may negatively impact general cognition, and the best responses to these treatments were observed in patients with AD rather than those with mild cognitive impairment (MCI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis. Chu, CS., Li, CT., Brunoni, AR., et al.[2021]

In a study involving 22 patients with mild cognitive impairment (MCI), repetitive Transcranial Magnetic Stimulation (rTMS) was found to significantly enhance the effects of Cognitive Stimulation (CS) as measured by the Montreal Cognitive Assessment (MoCA).

The study consisted of 30 sessions over 10 weeks, and while the active group showed significant improvements, the sham group did not, indicating that rTMS may be a beneficial tool for cognitive enhancement in MCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial magnetic stimulation as an enhancer of cognitive stimulation sessions on mild cognitive impairment: Preliminary results. Gy, RR., Jv, RL., J, RG., et al.[2021]

Cognitive Training (CT) in patients with Mild Cognitive Impairment (MCI) and early Alzheimer's Disease (AD) showed variable effects on brain structure and function, with some studies indicating increased cortical thickness and grey matter volumes, but no changes in hippocampal volumes.

The review included 19 studies, highlighting significant heterogeneity and variable quality, suggesting that while CT may lead to changes in brain activation and connectivity, more robust research is needed to clearly link these changes to clinical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging Outcomes in Studies of Cognitive Training in Mild Cognitive Impairment and Early Alzheimer's Disease: A Systematic Review. Beishon, L., Intharakham, K., Swienton, D., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) can effectively improve cognitive function and behavioral symptoms in dementia patients, as demonstrated in a case where a patient showed significant improvement after switching from 1 Hz to 10 Hz rTMS.

While rTMS is generally beneficial, it can lead to adverse reactions such as seizures; however, adjusting the treatment parameters (like reducing the frequency) can help mitigate these risks and continue to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report. Yang, Z., Zhou, Y.[2023]

In a study involving 15 Alzheimer's disease patients, those receiving repetitive transcranial magnetic stimulation combined with cognitive training (rTMS-COG) showed significant improvements in cognitive scores after 6 weeks and 4.5 months compared to a placebo group.

The treatment was found to be safe and effective, with notable enhancements in cognitive function and overall clinical impression, while the placebo group experienced mild worsening in their scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: a randomized, double-blind study. Rabey, JM., Dobronevsky, E., Aichenbaum, S., et al.[2021]

Transcranial direct current stimulation (tDCS) was found to be safe and well-tolerated in a study involving 20 patients with mild or major neurocognitive disorders, with an attrition rate of 0% and no serious adverse events reported.

However, the study did not find any statistically significant improvements in cognitive functioning when comparing the active tDCS group to the sham group, indicating that tDCS may not enhance cognitive performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. Inagawa, T., Yokoi, Y., Narita, Z., et al.[2022]

This study will evaluate the effectiveness of home-based computerized cognitive training (CCT) in improving cognitive abilities in 100 patients with mild cognitive impairment (MCI) over 12 weeks, with follow-up booster sessions for up to 78 weeks.

The trial aims to assess not only cognitive improvements but also changes in brain structure and function, specifically looking at hippocampal volume and the default mode network, using MRI scans, making it a comprehensive approach to understanding the impact of CCT on MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial. D'Antonio, J., Simon-Pearson, L., Goldberg, T., et al.[2020]

In a study involving 34 patients with mild cognitive impairment (MCI), those receiving 20 days of anodal transcranial direct current stimulation (tDCS) showed significant improvements in cognitive functions, including episodic verbal memory and overall cognitive function, compared to a sham group.

The results suggest that anodal tDCS may enhance cognitive symptoms in MCI patients, indicating its potential as a therapeutic tool, although further research is needed to clarify the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. Fileccia, E., Di Stasi, V., Poda, R., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials. [2021]

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

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Effect of transcranial magnetic stimulation as an enhancer of cognitive stimulation sessions on mild cognitive impairment: Preliminary results. [2021]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Neuroimaging Outcomes in Studies of Cognitive Training in Mild Cognitive Impairment and Early Alzheimer's Disease: A Systematic Review. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) in Mild Cognitive Impairment: Effects on Cognitive Functions-A Systematic Review. [2023]

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

Enhancing cognitive training effects in Alzheimer's disease: rTMS as an add-on treatment. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report. [2023]

8. Austria pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: a randomized, double-blind study. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Transcranial Direct Current Stimulation for Cognitive Rehabilitation in Patients With Mild or Major Neurocognitive Disorders: A Randomized Sham-Controlled Pilot Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial. [2020]

11. Italy pubmed.ncbi.nlm.nih.gov

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study. [2020]