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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining deep transcranial magnetic stimulation (dTMS) with cognitive training can improve memory and thinking skills in individuals with early memory concerns. dTMS uses a magnetic field to gently stimulate brain areas linked to cognitive resilience. Participants will receive either real dTMS or a sham (placebo) version, along with computer-based brain exercises. Suitable candidates are older adults, aged 55 to 70, with family histories of Alzheimer's and personal concerns about memory changes. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance cognitive health.

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 prior data suggests that this technique is safe for cognitive training?

A previous study found deep transcranial magnetic stimulation (dTMS) to be safe and well-tolerated, with serious side effects being rare. This technique uses a magnetic field to gently stimulate the brain and has been safely used to treat conditions like depression.

For the cognitive training part, research has shown it to be safe and effective for improving brain function in older adults. It involves using computer programs to keep the brain active and engaged.

Both treatments have undergone prior study and are generally considered safe for humans, based on past research findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of deep transcranial magnetic stimulation (dTMS) and cognitive training for mild cognitive impairment because it offers a novel approach compared to current treatments like medications or lifestyle changes. Unlike traditional options, dTMS uses magnetic fields to stimulate specific brain regions, potentially enhancing brain function and cognitive abilities. This non-invasive treatment, combined with computerized cognitive training, aims to directly improve brain health and could provide more immediate and noticeable cognitive benefits. This approach could be particularly appealing because it targets the brain's activity directly and may work faster or more effectively than current methods.

What evidence suggests that dTMS and cognitive training could be effective for mild cognitive impairment?

Research shows that deep transcranial magnetic stimulation (dTMS) can improve thinking and memory in people with cognitive difficulties. In this trial, participants will receive either dTMS or a sham intervention, both followed by cognitive training. Studies indicate that dTMS reduces certain symptoms, especially when combined with other treatments. Evidence suggests cognitive training can boost memory in people with mild cognitive impairment (MCI). Specifically, a review found that computerized cognitive training improved both verbal and visual memory. Combining these treatments might enhance brain functions in those experiencing cognitive decline. ^{6 7 8 9 10}

Who Is on the Research Team?

Linda Mah

Principal Investigator

Baycrest Rotman Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2760033/

Computer-Based Cognitive Training for Mild ... Seventy-seven percent of subjects completed the training, even though it involved a substantial time commitment of 90-100 minutes/day, 5 days/week for 6 weeks.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6701629/

a systematic review and meta-analysis - PMC - PubMed Central This meta-analysis provides evidence that CCT improves cognitive function in older people with MCI. However, the long-term transfer of these improvements

3. nature.com nature.com/articles/s41746-023-00987-5

Computerized cognitive training for memory functions in ... Among 1489 participants with MCI, CCT showed improvements in verbal memory (SMD (95%CI) = 0.55 (0.35–0.74)), visual memory (0.36 (0.12–0.60)), ...

4. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-024-03647-x

Individualised computerised cognitive training (iCCT) for ... By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months.

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/dad2.12626

Five‐year effects of cognitive training in individuals with mild ... Cognitive training reduced the 5-year memory decline of persons with MCI. Cognitive training also reduced decline on the Montreal Cognitive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7732551/

Advancing Computerized Cognitive Training for MCI and ... The FDA guidance categorizes early AD into three stages—Stage 1 (pathological changes but no clinical deficits), Stage 2 (mild cognitive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5702161/

Computerized cognitive stimulation and engagement ... Mild cognitive impairment (MCI) is associated with a higher risk of dementia and is becoming a topic of interest for pharmacological and nonpharmacological ...

8. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2016.16030360

Computerized Cognitive Training in Older Adults With Mild ... Previous meta-analyses indicate that computerized cognitive training (CCT) is a safe and efficacious intervention for cognition in older adults.

9. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-023-01292-9

Effects of computerized cognitive training on structure ... Computerized cognitive training (CCT) has been demonstrated to be a safe and effective means of improving neurocognitive functions [15]. A few ...

10. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1384318/full

Intervention of computer-assisted cognitive training ... Computerized cognitive training combined with occupational therapy can improve patients' cognitive status, enhance their compliance with continuing care.