TMS for Cognitive Decline

Overseen By Anna Du, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Clozapine, Bupropion, others

Disqualifiers: Head trauma, Neurologic condition, others

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

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a type of non-invasive brain stimulation, called repetitive Transcranial Magnetic Stimulation (rTMS), affects motivation, memory, and brain function in older adults. rTMS gently influences the brain area linked to thinking and will be assessed using behavior tests and MRI scans. The trial may suit native English speakers aged 40-99 who are either cognitively healthy or show early signs of Alzheimer's disease and are open to participating in brain imaging and cognitive tests.

As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research on brain health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that can cause seizures, like clozapine or high doses of bupropion.

What prior data suggests that this non-invasive brain stimulation is safe for cognitive function?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe. One study found that rTMS improved memory and thinking skills in people with Alzheimer's disease without major side effects. Another review found that rTMS is safe and effective for enhancing memory in individuals with mild memory problems. These studies suggest that rTMS is well-tolerated, with no significant harmful effects reported. Overall, rTMS appears to be a safe option for those considering participation in clinical trials focused on brain health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Transcranial Magnetic Stimulation (TMS) for cognitive decline because it offers a non-invasive way to potentially enhance brain function. Unlike traditional medications that may take weeks to show effects and often come with side effects, TMS uses magnetic fields to stimulate nerve cells in the brain, which could lead to quicker improvements in cognitive abilities. Additionally, this method targets specific brain areas without affecting the entire body, reducing the risk of systemic side effects that are common with oral medications. Overall, TMS represents a promising alternative that could complement or even replace current treatments for cognitive decline.

What evidence suggests that rTMS might be an effective treatment for cognitive decline?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) can improve thinking and memory. One study found that rTMS led to better scores on memory and thinking tests for individuals with mild memory problems and early Alzheimer's disease. Another study demonstrated that rTMS enhances brain function and adaptability. Some research suggests that rTMS can boost memory and thinking skills by supporting brain health. However, not all studies agree; one review found no major improvement compared to a sham treatment. Overall, promising evidence indicates that rTMS could enhance brain function in those at risk for memory and thinking problems. Participants in this trial will receive both active and sham rTMS in a within-subject crossover design to further evaluate these effects. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for older adults who are either cognitively healthy or have mild cognitive impairment, which can be an early sign of Alzheimer's. Participants should not have any serious medical conditions and must be able to attend multiple study visits over several weeks.

Inclusion Criteria

Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points

I am an older adult with normal thinking abilities or have early Alzheimer's without symptoms.

I am a native English speaker.

Exclusion Criteria

Another major neurologic or psychiatric condition

Longstanding premorbid history (i.e. longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed

Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline and rTMS Treatment

Participants undergo a baseline visit followed by 10 days of daily rTMS study visits and an evaluation visit

2 weeks

1 baseline visit, 10 daily rTMS visits, 1 evaluation visit

Break

Participants take a 2-week break from the study

2 weeks

Second Baseline and rTMS Treatment

Participants return for another baseline visit, 10 days of rTMS, and a final evaluation visit

2 weeks

1 baseline visit, 10 daily rTMS visits, 1 final evaluation visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS
• Sham rTMS

Trial Overview The study is testing repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, to see if it improves memory and cognition in aging individuals and those with preclinical Alzheimer's disease. It involves daily sessions over two periods of 10 days each.

How Is the Trial Designed?

Group I: Active TMS Experimental Treatment 1 Intervention

All participants will receive the same study interventions in a within-subject crossover design.

Group II: Sham TMS Placebo Group 1 Intervention

All participants will receive the same study interventions in a within-subject crossover design.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

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]

In a study involving 19 middle-aged and elderly patients with refractory depression, those receiving active repetitive transcranial magnetic stimulation (rTMS) showed significant improvements in cognitive flexibility compared to those receiving sham treatment.

The active rTMS was specifically targeted at the anterior portion of the left middle frontal gyrus, suggesting a potential mechanism for enhancing cognitive function in patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved executive functioning following repetitive transcranial magnetic stimulation. Moser, DJ., Jorge, RE., Manes, F., et al.[2019]

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]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

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) was found to be safe for a patient with an implanted subdural cortical electrode, showing no serious adverse effects during treatment.

Ex-vivo experiments indicated that rTMS caused only a slight increase in coil temperature and no displacement of the electrodes, suggesting that rTMS can be safely applied in clinical settings for patients with such implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case. Phielipp, NM., Saha, U., Sankar, T., et al.[2019]

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]

Repetitive transcranial magnetic stimulation (rTMS) significantly improved cognitive function in older patients with mild to moderate Alzheimer's disease, based on a meta-analysis of seven randomized controlled trials involving 194 participants.

rTMS is considered a safe and well-tolerated alternative intervention for cognitive impairment, showing a moderate effect size in enhancing cognition compared to sham treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation on improvement of cognition in elderly patients with cognitive impairment: a systematic review and meta-analysis. Cheng, CPW., Wong, CSM., Lee, KK., et al.[2018]

Citations

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Effects of Repetitive Transcranial Magnetic Stimulation in ... This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725000230

Effects of repetitive transcranial magnetic stimulation (rTMS ... The meta-analysis revealed no significant improvement in cognitive impairment with active rTMS compared to sham rTMS across multiple cognitive ...

3. journals.lww.com journals.lww.com/jops/fulltext/2025/01000/effectiveness_of_repetitive_transcranial_magnetic.12.aspx

Effectiveness of Repetitive Transcranial Magnetic... The study found that active rTMS led to significant improvement in MMSE scores in people with MCI and early AD.

4. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1254523/full

Effects of repetitive transcranial magnetic stimulation ... Current studies have shown that rTMS-CT training can improve patients' cognitive function in four aspects, namely, promoting neuroplasticity, improving brain ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818365

Effectiveness of Personalized Hippocampal ... Conclusions and Relevance This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and ...

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/S1697260024000176/pdf

Efficacy and safety of repetitive Transcranial Magnetic ... Our study showed that rTMS over frontal regions and tDCS over temporal regions can improve memory abilities in people with AD. However, the prolonged effect of ...

8. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02493-8

Therapeutic potential and mechanisms of repetitive ... This review synthesizes current evidence supporting rTMS as an effective intervention for alleviating clinical symptoms of Alzheimer's disease.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07036328

Transcranial Magnetic Stimulation to Slow Down Cognitive ... The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is ...

10. 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 ...