Repetitive Transcranial Magnetic Stimulation for Mild Cognitive Impairment

Overseen By Yu-Chin Chen, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Arizona

Disqualifiers: Stroke, Head injuries, Multiple sclerosis, others

Compensation: Varies

Number of Visits: 33

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new, non-invasive brain stimulation method called repetitive transcranial magnetic stimulation (rTMS) to assist individuals with mild cognitive impairment (MCI) and those at risk for Alzheimer's disease (AD). The researchers aim to find ways to prevent or slow memory and thinking problems. Participants will receive either a real or sham (fake) treatment to evaluate its effectiveness. Ideal candidates are right-handed, English-speaking individuals who have reported memory issues and can attend sessions daily for four weeks. As an unphased trial, this study offers the chance to contribute to groundbreaking research that could lead to new preventive treatments for memory issues.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that repetitive transcranial magnetic stimulation (rTMS) is safe for mild cognitive impairment?

Research shows that transcranial magnetic stimulation (TMS) is generally safe for individuals with memory and thinking problems. Studies have found that TMS can enhance memory and thinking skills, benefiting those with mild cognitive impairment (MCI). Importantly, the treatment is well-tolerated, with most individuals experiencing no significant side effects.

Regarding theta burst stimulation (TBS), a type of TMS, research also supports its safety. One study found that high-dose TBS, tailored to individual needs, aided cognitive recovery after a stroke without major issues. Another study demonstrated that TBS could safely enhance brain function, potentially supporting brain health.

Overall, these findings suggest that TBS and TMS are safe options for those at risk of cognitive decline, such as individuals with MCI. It is essential to consult healthcare professionals to determine if this treatment is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) for Mild Cognitive Impairment is unique because it uses magnetic fields to stimulate nerve cells in the brain, which is different from the typical medications like cholinesterase inhibitors. Researchers are excited about these treatments because they offer a non-invasive approach that directly targets brain activity, potentially improving cognitive function without the side effects associated with drugs. Moreover, the trial includes different forms of theta burst stimulation (TBS), such as excitatory and inhibitory TBS, which allows researchers to explore how varying stimulation patterns might enhance or suppress brain activity to optimize cognitive improvements. This approach could lead to personalized treatments based on individual brain responses.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment?

Research shows that theta burst stimulation (TBS) might improve thinking and memory in people with mild cognitive impairment (MCI). This trial will explore different types of TBS, including excitatory and inhibitory TBS, to assess their effects on cognitive function. Some studies have found that intermittent TBS (iTBS) can enhance memory and thinking skills in people with MCI and even in the early stages of Alzheimer's disease. For example, one study found that iTBS improved skills like decision-making and focus. Additionally, evidence suggests that iTBS could boost brain function in people at risk of diseases affecting the brain. These findings offer hope for delaying symptoms of cognitive decline. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals aged 50-80 with mild cognitive impairment (MCI), who can attend daily sessions for 4 weeks, and haven't been in another study recently. They should have certain scores on cognitive tests like the MMSE or MoCA, be right-handed, and not have dementia.

Inclusion Criteria

You must be able to speak English.

You have not participated in another research study that involves receiving treatment within the past 6 months.

You have difficulty with thinking and memory as shown by certain tests, such as the MMSE or MoCA, with scores between 24-27 or 18-26, respectively. Or, you have a Clinical Dementia Rating Scale score of 0.5.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Intervention

Participants receive 30 intervention sessions of TMS across three different protocols, with MRI and cognitive tasks before and after each protocol

3 months

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including brain imaging and neuropsychological assessments

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• TBS
• TMS

Trial Overview The study aims to prevent cognitive decline using repetitive transcranial magnetic stimulation (rTMS). It involves personalized brain stimulation guided by MRI imaging to enhance memory and delay Alzheimer's disease progression in those at high risk.

How Is the Trial Designed?

Group I: Inhibitory TBS Experimental Treatment 1 Intervention

Inhibitory TBS

Group II: Excitatory TBS Experimental Treatment 1 Intervention

Excitatory TBS

Group III: Sham TBS Placebo Group 1 Intervention

Sham TBS

TBS is already approved in United States for the following indications:

Approved in United States as TMS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 21 patients with amnestic mild cognitive impairment (aMCI), repetitive transcranial magnetic stimulation (rTMS) significantly improved cognitive performance and altered functional connectivity within the default mode network (DMN) compared to a sham treatment.

The changes in DMN connectivity, particularly a decrease in connectivity, were linked to cognitive improvements, suggesting that baseline DMN activity could predict how well patients respond to rTMS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation Induced Hypoconnectivity Within the Default Mode Network Yields Cognitive Improvements in Amnestic Mild Cognitive Impairment: A Randomized Controlled Study. Cui, H., Ren, R., Lin, G., et al.[2020]

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]

Low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improved cognitive function in 36 patients with post-stroke cognitive impairment (PSCI) after 8 weeks of treatment, compared to a control group that received placebo stimulations.

The treatment group showed greater improvements in cognitive assessments and neural activity, as indicated by changes in LOTCA scores and P300 latencies and amplitudes, suggesting that rTMS may enhance neural electrical activity in the cerebral cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral activity manipulation of low-frequency repetitive transcranial magnetic stimulation in post-stroke patients with cognitive impairment. Yingli, B., Zunke, G., Wei, C., et al.[2022]

Repetitive Transcranial Magnetic Stimulation (rTMS) targeting the left parietal cortex significantly improved memory performance in a patient with amnestic Mild Cognitive Impairment (aMCI).

The memory improvement was not only immediate but also sustained, remaining significant 24 weeks after the stimulation began, suggesting a lasting effect of rTMS on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment. Cotelli, M., Calabria, M., Manenti, R., et al.[2016]

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 40 patients with Parkinson's disease and mild cognitive impairment, combining repetitive transcranial magnetic stimulation (rTMS) with virtual reality (VR) training led to significantly greater improvements in cognitive functions, particularly in memory and executive function, compared to rTMS alone.

The rTMS-VR group showed enhanced cognitive benefits immediately after treatment and maintained improvements in delayed memory scores at a 3-month follow-up, suggesting that this combined approach could be an effective strategy for cognitive rehabilitation in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of Virtual Reality into Transcranial Magnetic Stimulation Improves Cognitive Function in Patients with Parkinson's Disease with Cognitive Impairment: A Proof-of-Concept Study. Cheng, TC., Huang, SF., Wu, SY., et al.[2022]

In a double-blind, sham-controlled trial involving 24 patients with amnestic mild cognitive impairment (aMCI), high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improved cognitive function as measured by the Montreal Cognitive Assessment after 4 weeks of treatment.

The rTMS treatment also led to notable changes in brain activity, specifically increasing the amplitude of low-frequency fluctuations in key cognitive areas, suggesting that rTMS may enhance cognitive function by altering brain activity patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial. Yuan, LQ., Zeng, Q., Wang, D., et al.[2021]

Citations

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

Effects of intermittent theta-burst stimulation on cognition ... These findings suggest that iTBS can produce delayed cognitive enhancement in individuals with amnestic MCI and very mild AD, while the impact ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125000042

Neurocognitive effects of theta burst stimulation for ... Results suggested that TBS for TRD may produce neurocognitive enhancement across specific neurocognitive domains including executive functioning, attention, ...

3. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-025-01625-5

A pilot randomized controlled double-blind trial of intermittent ... This innovative study aims to test the feasibility of iTBS as a cognitive enhancement strategy in MCI.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05327257

NCT05327257 | iTBS rTMS in Mild Cognitive Impairment The purposes of this research are to test whether it is feasible to administer a treatment protocol called intermittent theta burst stimulation (iTBS) ...

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

Efficacy and Safety of Transcranial Magnetic Stimulation on ... The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000403

Efficacy and safety of high-dose and personalized TBS on ... This study highlights the efficacy and safety of high-dose iTBS targeting the individualized FCN for post-stroke cognitive recovery.

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1436448/full

The effects of repetitive transcranial magnetic and ... This meta-analysis suggests that rTMS and tDCS are safe and efficient tools to improve memory functions in patients with MCI, while rTMS had a larger effect ...