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

Trial Summary

What is the purpose of this trial?

The ultimate goal of this study is to develop non-invasive, painless repetitive transcranial magnetic stimulation (rTMS) protocols to prevent cognitive decline in patients with mild cognitive impairment (MCI) and cognitively normal individuals at high risk of developing Alzheimer's disease (AD). Currently, 1 in 9 adults over the age of 65 have AD, which currently totals more than 5 million Americans and this number is expected to rise as high as 16 million by 2050. MCI is a clinical syndrome that represents the gray area between healthy aging and dementia. Those with amnestic MCI (aMCI) have memory problems more severe than normal for their age and education, but their symptoms are not as severe as those of people with AD. Patients with aMCI are at high risk for AD. Notably, roughly half of those with MCI will continue to progress and convert to clinical dementia within 3 years. Alternatively, it is also worthwhile to study cognitively healthy older adults who carry genes that may increase the risk of AD. The frequency of the human APOE gene ε4 allele increases in patients with AD and the ε4 allele is also associated with an earlier age of disease onset. Currently, there are no known therapies that can effectively modify the progression and hallmark symptoms of AD. Therefore, it is crucial to provide an early intervention in patients with aMCI to delay or prevent the progression to AD. More specifically, this project has two specific aims: 1. To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI) 2. To identify potential personalized cognitive enhancement strategy (such as dosage or patterns) of Transcranial Magnetic Stimulation (TMS) in MCI. Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals and people with clinical conditions. With these practices, researchers can safely stimulate specific regions of the brain to explore causal relationships that comprise the brain's circuitry and modulate behavior.

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation for Mild Cognitive Impairment?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) can improve cognitive function in people with mild cognitive impairment, as seen in studies where it enhanced memory and cognitive test scores. It has also been effective in improving cognitive function in patients with Parkinson's disease and post-stroke cognitive impairment. ^{1 2 3 4 5}

How does the treatment repetitive transcranial magnetic stimulation (rTMS) differ from other treatments for mild cognitive impairment?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it is a noninvasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially enhancing cognitive function in patients with mild cognitive impairment. Unlike other treatments, rTMS can alter brain activity in cognitive-related areas, which may lead to improvements in cognitive function. ^{1 2 3 6 7}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. 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]

2. Netherlands 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. [2022]

3. India 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebral activity manipulation of low-frequency repetitive transcranial magnetic stimulation in post-stroke patients with cognitive impairment. [2022]

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

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment. [2016]

6. Netherlands 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. [2020]

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]