RTMS for Dementia

(rTMS for demen Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Seizure-inducing drugs

Disqualifiers: Seizure disorder, Psychosis, Substance abuse, others

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

Compensation: Varies

Number of Visits: 10

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain treatment, can enhance thinking and memory in individuals with mild to moderate cognitive issues, including early dementia. Researchers aim to understand how the treatment effects relate to the initial severity of cognitive problems. Eligible participants are veterans aged 55 or older, diagnosed with mild cognitive impairment or dementia likely due to Alzheimer's, and have a stable living situation for regular clinic visits. As an unphased trial, this study provides a unique opportunity to contribute to understanding and potentially improving cognitive health in veterans.

Will I have to stop taking my current medications?

The trial requires that if you are on a medication for cognition, your dose must be stable for at least 4 weeks before starting and remain stable during the treatment phase. You may need to stop medications that increase the risk of seizures at least two weeks before treatment.

What prior data suggests that rTMS is safe for patients with neurodegenerative conditions?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated. In studies, serious side effects were rare, with only a few participants experiencing major issues. Most participants did not encounter significant problems with rTMS.

Furthermore, a meta-analysis, which combines results from several studies, confirmed these findings, supporting the safety of rTMS for treating cognitive problems like dementia and mild cognitive impairment. Overall, the evidence suggests that rTMS could be a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about repetitive transcranial magnetic stimulation (RTMS) for dementia because it offers a non-invasive approach that directly targets brain activity. Unlike standard dementia treatments that primarily rely on medications like cholinesterase inhibitors and memantine, RTMS uses magnetic fields to stimulate nerve cells, potentially improving cognitive function without the side effects of drugs. This innovative method could provide a new avenue for enhancing brain function, offering hope for more effective management of dementia symptoms.

What evidence suggests that rTMS is effective for improving cognitive function in dementia?

Research has shown that repetitive transcranial magnetic stimulation (rTMS), which participants in this trial may receive, can improve thinking and memory in people with cognitive problems. One study found that rTMS significantly boosted overall mental abilities and skills needed for daily life. Another study demonstrated improvements in thinking and daily functioning when targeting specific brain areas. Using rTMS over a long period has also been linked to slowing memory loss in Alzheimer's patients. Overall, evidence suggests that rTMS may help with memory and thinking issues related to dementia. ^{2 6 7 8 9}

Who Is on the Research Team?

Jauhtai J Cheng, MD

Principal Investigator

VA Palo Alto Health Care System, Palo Alto, CA

Are You a Good Fit for This Trial?

This trial is for veterans aged 55 or older with mild to moderate cognitive impairment or dementia likely due to Alzheimer's, who can attend clinic visits and have stable medication doses. They must be able to consent and not have pacemakers, cochlear implants, metal in the brain, seizure risks, severe hearing issues, active CNS diseases increasing seizure risk, recent traumatic brain injury or current psychosis.

Inclusion Criteria

Ability to obtain a Motor Threshold, determined during the screening process

I can read and understand the consent form and agree to participate in the study.

I am a veteran aged 55 or older with Mild Cognitive Impairment or Alzheimer's.

Exclusion Criteria

Have an implanted device deep brain stimulation or metal in the brain

Active current suicidal intent or plan as determined by patient report or chart review

Traumatic brain injury within the last two months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and biomarker analysis

4 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RTMS
• sham

Trial Overview

The study tests whether repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in patients with neurodegenerative conditions leading to dementia. It also examines if the severity of initial cognitive impairment affects rTMS response. Participants are randomly assigned to receive either rTMS or a sham (placebo-like) procedure.

How Is the Trial Designed?

Group I: RTMS Experimental Treatment 1 Intervention

repetitive transcranial magnetic stimulation

Group II: sham Placebo Group 1 Intervention

sham noise to block the sound of treatment

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study involving 42 Japanese patients with Alzheimer's dementia, 4 weeks of repetitive transcranial magnetic stimulation (rTMS) at 120% resting motor threshold showed significant efficacy in improving cognitive function for patients with MMSE scores ≥ 15, with 41.7% of participants experiencing a notable improvement compared to 0% in the Sham group.

The treatment was found to be safe, with no serious adverse events reported, suggesting that rTMS could be a promising intervention for patients with moderate to mild Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan. Saitoh, Y., Hosomi, K., Mano, T., et al.[2023]

In a study involving 19 participants, both a simple rTMS protocol targeting the left dorsolateral prefrontal cortex (lDLPFC) and a complex protocol involving six brain regions showed similar improvements in cognitive function, behavior, and functionality after 3 weeks of treatment.

The benefits of rTMS were maintained for an additional 4 weeks without further treatment, suggesting that targeting the lDLPFC alone may be sufficient for clinical improvement in Alzheimer's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer's disease. Alcalá-Lozano, R., Morelos-Santana, E., Cortés-Sotres, JF., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

In a pilot study involving 30 Alzheimer's disease patients, focal repetitive transcranial magnetic stimulation (rTMS) using the H2-coil showed a trend toward improved cognitive function, with a mean decrease of -1.01 points on the ADAS-Cog scale after treatment, although this effect was not sustained two months post-treatment.

The study indicates that rTMS with the H2-coil is safe and feasible for Alzheimer's patients, suggesting potential cognitive benefits that warrant further investigation in larger trials, especially when combined with cognitive rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study. Leocani, L., Dalla Costa, G., Coppi, E., 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]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

Citations

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The therapeutic efficacy of transcranial magnetic stimulation in ...

It was found that rTMS significantly improved global cognitive function (SMD = 0.24, 95%CI, 0.12 to 0.36, P = 0.0001) and daily living ability ( ...

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The first significant finding was improved cognitive and functional performance after hippocampal network targeted stimulation. We found a ...

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The overall results show significant cognitive improvement after treatment up to two months post-treatment with either sham or active coils. The results show ...

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Fifty-two weeks of PC-rTMS may slow down the impairment of cognitive functions, activities of daily living and behavioral disturbances in patients with mild-to ...

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frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1536573/full

Comparative efficacy of rTMS on different targets in ...

The results showed that rTMS significantly improved cognitive function score in AD patients, with an SMD of 0.27 (95% CI = 0.14–0.41; z = 3.95; ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11306417/

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TMS was safe and well tolerated with infrequent serious adverse events. Keywords: cognition, dementia, meta-analysis, MCI, mild cognitive ...

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This is a proof-of-concept study to evaluate the safety and effect of occipital lobe stimulation in patients with Lewy body dementia. Over a ...

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Results showed that rTMS had a better effect when the follow-up time was > 6 weeks (SMD = 0.67, 95%CI, 0.05 to 1.30, P = 0.04) than ≤6 weeks ( ...