TMS for Cognitive Decline

Overseen By Anna Du, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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

Trial Summary

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 data supports the effectiveness of the treatment Active rTMS for cognitive decline?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive function in older adults with cognitive impairment and Alzheimer's disease. In one study, patients receiving real rTMS showed a trend toward improved cognitive scores, suggesting potential benefits for cognitive decline. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) has been used safely in both healthy individuals and those with various brain conditions since the 1990s. While it can cause some adverse events like seizures, safety guidelines have been established and updated over the years to minimize risks. Generally, rTMS is considered safe when used according to these guidelines. ^{6 7 8 9 10}

How does the treatment rTMS differ from other treatments for cognitive decline?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can improve cognitive functions like memory and attention. Unlike medications, rTMS is non-invasive and does not involve taking drugs, making it a novel option for those with cognitive decline. ^{1 3 4 5 11}

What is the purpose of this trial?

In this research study we want to learn more about the effects of non-invasive brain stimulation on motivation, memory, and brain-network function in cognitively unimpaired older adults and individuals with preclinical Alzheimer's disease. This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls cognition. Changes resulting from this stimulation will be measured with behavioral tests, as well as by taking brain images with Magnetic Resonance Imaging (MRI). Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: CN and participants with preclinical AD Experimental Treatment 2 Interventions

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+

Findings from Research

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) 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]

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) 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) 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]

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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and benefits of distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75 years of age: a pilot study. [2022]

4. England 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Improved executive functioning following repetitive transcranial magnetic stimulation. [2019]

6. Netherlands 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. [2019]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

9. Ireland 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. [2022]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) for geriatric depression. [2023]