Transcranial Magnetic Stimulation for Alzheimer's Disease

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: HealthPartners Institute

Must be taking: Cholinesterase inhibitors, Memantine

Disqualifiers: Non-AD dementia, Seizure disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for Alzheimer's disease using transcranial magnetic stimulation (TMS), which employs magnetic fields to stimulate brain activity. The study aims to determine if this method can improve brain function compared to a sham treatment. It may suit individuals with mild Alzheimer's disease who have been diagnosed and have brain scans showing signs of the condition. Participants should also maintain a stable medication routine for at least a month. The specific type of TMS being tested is Intermittent Theta Burst Stimulation. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for Alzheimer's disease.

Will I have to stop taking my current medications?

The trial requires that participants have been on a stable dose of cholinesterase inhibitors and memantine for at least one month, so you will not need to stop these medications.

What prior data suggests that transcranial magnetic stimulation is safe for Alzheimer's disease?

Research has shown that a treatment called intermittent theta burst stimulation (iTBS) might be safe for people with Alzheimer's. In earlier studies, individuals with very mild Alzheimer's or mild memory problems tolerated iTBS well, with no major safety issues. Another study on mice with Alzheimer's found that iTBS improved brain health without serious side effects.

These results are encouraging, but more research is needed to fully understand its safety for everyone. Prospective trial participants should consult their doctor about any questions or concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about intermittent theta burst stimulation (iTBS) for Alzheimer's disease because it offers a novel approach compared to traditional treatments like cholinesterase inhibitors and NMDA receptor antagonists. Unlike these medications, which primarily focus on chemical imbalances in the brain, iTBS uses magnetic fields to target specific brain regions linked to Alzheimer's. This technique aims to improve brain connectivity and function, potentially offering a non-invasive and drug-free alternative to current options. Additionally, iTBS has the potential to provide benefits in a relatively short timeframe, with treatments conducted over a two-week period.

What evidence suggests that transcranial magnetic stimulation might be an effective treatment for Alzheimer's disease?

Research has shown that intermittent theta burst stimulation (iTBS), a treatment participants in this trial may receive, might improve thinking and memory in people with Alzheimer's disease. Studies have found that this non-invasive treatment can ease memory and thinking problems and may also help with depression, which is common in Alzheimer's patients. In animal studies, iTBS reduced brain damage, with benefits lasting for a few months. Other research suggests that repeating iTBS every few months might help slow memory and thinking decline. Overall, iTBS offers a promising new way to manage Alzheimer's symptoms, alongside traditional medications like donepezil and memantine. ^{1 2 3 6 7}

Who Is on the Research Team?

Bhavani Kashyap, MBBS, PhD

Principal Investigator

HealthPartners Institute

Are You a Good Fit for This Trial?

This trial is for people aged 40-90 with Mild Cognitive Impairment or mild Alzheimer's Disease, scoring over 24 on the MMSE and having a CDR of 0.5-1. Participants must show evidence of amyloidosis in the brain and have been on a stable dose of Alzheimer's medications for at least one month.

Inclusion Criteria

I have been diagnosed with mild cognitive impairment or mild Alzheimer's disease.

Mini Mental Status Examination (MMSE) >24

Clinical Dementia Rating (CDR) 0.5-1

Exclusion Criteria

My condition is a type of dementia, but not Alzheimer's disease.

I have a seizure disorder.

Inability to tolerate resting state-function magnetic resonance imaging (rs-fMRI)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 treatments of intermittent theta burst stimulation (iTBS) or sham over a 2-week period

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-7 weeks

Open-label extension (optional)

Participants who received the sham treatment may opt into continuation of treatment with iTBS without further data collection

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation

Trial Overview The study tests if transcranial magnetic stimulation (TMS) using intermittent theta burst stimulation (iTBS) can be an effective non-invasive treatment compared to a sham (placebo-like) procedure in individuals with early-stage Alzheimer's Disease.

How Is the Trial Designed?

Group I: Intermittent theta burst stimulation Experimental Treatment 1 Intervention

Subjects will receive treatment with intermittent theta burst stimulation (iTBS) with the active coil. There will be a total of 5 treatments over a 2-week period. All subjects will receive iTBS to the 8Av region. TBS treatment will also be provided for two additional sites within the large-scale brain networks (LSBNs) that is found to contain the greatest number of connectivity anomalies. Total participation will be 6-9 weeks.

Group II: Sham device Placebo Group 1 Intervention

Subjects will receive treatment with sham coil. There will be a total of 5 treatments over a 2-week period. Coil will be placed over the same region as the experimental group. Total participation will be 6-9 weeks. An open-label extension will be offered to participants that received the sham (control) treatment without further data collection.

Who Is Running the Clinical Trial?

HealthPartners Institute

Lead Sponsor

Trials

196

Recruited

3,721,000+

Published Research Related to This Trial

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

Theta-burst stimulation appears to significantly reduce the severity of unilateral spatial neglect in stroke patients, based on a systematic review of nine studies involving 148 participants.

Despite the promising results, the evidence is limited and inconsistent due to variations in study protocols and terminology, making it difficult to draw definitive conclusions about its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of theta-burst stimulation on unilateral spatial neglect following stroke: a systematic review. Cotoi, A., Mirkowski, M., Iruthayarajah, J., et al.[2019]

Intermittent theta burst stimulation (iTBS) significantly reduces amyloid-beta (Aβ) accumulation in the brains of APP/PS1 mice, indicating its potential to mitigate Alzheimer's disease-related pathologies.

The treatment not only lowers Aβ levels by inhibiting its production and enhancing its degradation but also reduces neuroinflammation, neuronal cell death, and synaptic loss, suggesting long-lasting protective effects on brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effects of intermittent theta burst stimulation on Alzheimer's disease-type pathologies in APP/PS1 mice. Huang, H., Zhu, Y., Liao, L., et al.[2023]

Transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol (1200 pulses) significantly increased corticospinal excitability in the targeted primary motor cortex (M1) while inhibiting excitability in the opposite M1 for up to 30 minutes, indicating its potential for modulating motor function.

iTBS1200 also enhanced post-movement beta synchronisation in the stimulated M1, suggesting a link between this brain activity and improved motor output, while not affecting alpha and low gamma rhythms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent θ burst stimulation over primary motor cortex enhances movement-related β synchronisation. Hsu, YF., Liao, KK., Lee, PL., et al.[2011]

Theta-burst Stimulation (TBS) is a promising form of repetitive transcranial magnetic stimulation that can induce significant and lasting changes in brain activity with lower intensity and shorter duration than traditional methods, making it a potentially more efficient treatment option.

TBS may have therapeutic implications for neuropsychiatric disorders due to its ability to promote synaptic plasticity, although the exact neurobiological mechanisms, including processes like long-term potentiation and GABAergic modulation, are still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and applications of theta-burst rTMS on the human motor cortex. Cárdenas-Morales, L., Nowak, DA., Kammer, T., et al.[2009]

In a study involving 58 participants with mild to moderate Alzheimer's disease, intermittent theta burst stimulation (iTBS) was found to enhance gamma connectivity in the brain, which is linked to cognitive function.

Active iTBS treatment led to significant improvements in delayed recall on memory tasks, suggesting that this non-invasive stimulation technique could be a promising therapeutic approach for cognitive impairment in Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma connectivity predicts response to intermittent theta burst stimulation in Alzheimer's disease: a randomized controlled trial. Hoy, KE., Emonson, MRL., Bailey, NW., et al.[2023]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

Citations

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

Effects of intermittent theta-burst stimulation on cognition ... Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in alleviating cognitive symptoms in Alzheimer's disease (AD) ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0361923023001600

The long-term effects of intermittent theta burst stimulation ... These data indicate that 1 month of iTBS treatment ameliorates pathologies in the brain of AD mice for at least 2 months.

3. gpsych.bmj.com gpsych.bmj.com/content/37/1/e101106

Effects of a periodic intermittent theta burst stimulation in ... We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11331392/

Alzheimer's disease with depressive symptoms: Clinical ... The iTBS model of rTMS effectively treated AD with depression, improving depressive symptoms and cognitive function in patients without serious adverse ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/27706710.2025.2558557

The effects of priming intermittent theta-burst stimulation on ... Aim. Intermittent theta burst stimulation (iTBS) shows promise in alleviating cognitive dysfunction in neurodegenerative diseases.

6. 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.

7. medrxiv.org medrxiv.org/content/10.1101/2025.09.15.25335839v1

A systematic review of preclinical and clinical studies Alzheimer's disease and the therapeutic potential of theta burst stimulation: A systematic review of preclinical and clinical studies. View ...