Theta-burst Stimulation for Memory Improvement in Mild Cognitive Impairment

Overseen By Sonja Hiller

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must not be taking: Anticholinergics, Antihistamines, Benzodiazepines

Disqualifiers: Dementia, Stroke, Substance abuse, others

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

Compensation: Varies

Number of Visits: 9

Duration: 3 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if theta-burst stimulation, a type of transcranial magnetic stimulation, can improve memory in individuals with memory issues. Participants will receive either the actual brain stimulation or a placebo version that does not stimulate the brain. The trial targets those who have noticed memory problems but still live independently and are generally healthy. The goal is to assess whether this approach can enhance memory function safely and effectively. Participants will remain unaware of whether they receive the active treatment or the placebo. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new memory enhancement therapies.

Will I have to stop taking my current medications?

The trial requires that you do not change your use of medications for depression, anxiety, ADHD, or psychosis for one month before and during the study. If you are taking certain medications like anticholinergics, sedating antihistamines, or benzodiazepines, you may need to stop or adjust them, but this will be decided on a case-by-case basis.

What prior data suggests that this device is safe for memory improvement?

Research has shown that theta burst stimulation (TBS), a type of brain stimulation, is generally safe. Studies have found that targeting brain areas related to memory with TBS rarely causes serious side effects.

In one study on safety, researchers used a checklist to monitor negative effects, and participants handled the treatment well. Another study found that TBS could enhance certain brain functions without major issues.

Some individuals might experience mild side effects like headaches or scalp discomfort, but these typically resolve quickly. Overall, current research indicates that the treatment appears safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about theta-burst stimulation (TBS) for mild cognitive impairment because it offers a non-invasive approach that could potentially enhance memory function. Unlike traditional treatments that mainly rely on medications like cholinesterase inhibitors to manage symptoms, TBS uses magnetic pulses to stimulate specific brain areas, aiming to improve neural connectivity and function. This innovative technique could offer a quicker and more direct method to address cognitive decline, with the promise of fewer side effects compared to pharmacological options.

What evidence suggests that this device is effective for memory improvement in mild cognitive impairment?

Research has shown that theta-burst stimulation (TBS) might help improve memory in people with mild cognitive impairment (MCI). In this trial, participants will receive either Active TBS or Sham TBS. Studies have found that TBS can enhance thinking skills, particularly memory and attention. One study discovered that TBS led to delayed improvements in memory for those with amnestic MCI, where memory loss is the main issue. Another study noted that TBS could improve brain functions like decision-making and focus. Overall, TBS appears to be a promising non-invasive method to boost memory and thinking abilities. ^{3 6 7 8 9}

Who Is on the Research Team?

Nanthia Suthana

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for individuals aged 55-90 with mild cognitive impairment, who are in good health, right-handed, and speak English fluently. They should have memory complaints verified by specific tests and be able to consent to a long-term study. Excluded are those with dementia, major psychiatric or neurological disorders, substance abuse issues, certain medication use, or contraindications to MRI.

Inclusion Criteria

MMSE score > 24

Hamilton Depression score < 7

I can perform most daily activities without help.

Exclusion Criteria

I have been diagnosed with dementia.

Unwilling or unable to provide informed consent

Not right handed based on self-report or evaluation based on a standard report

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham transcranial magnetic stimulation to improve memory

3 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

3 visits (in-person)

Long-term follow-up

Participants undergo additional assessments to evaluate long-term effects of the treatment

2 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active Theta Burst Stimulation
• Sham Theta Burst Stimulation
• Theta Burst Stimulation

Trial Overview The trial examines whether brain stimulation using transcranial magnetic stimulation (TMS) can improve memory in people with mild cognitive impairment. Participants will be randomly assigned to receive either active TMS or sham (fake) treatment without knowing which one they're getting.

How Is the Trial Designed?

Group I: Active TBS Experimental Treatment 1 Intervention

Theta burst stimulation (TBS) will be delivered at 100% of motor threshold (MT).

Group II: Sham TBS Placebo Group 1 Intervention

Sham stimulation will be delivered at 0% of motor threshold (MT), with all other parameters matching the active TBS condition.

Active Theta Burst Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Repeated applications of Theta Burst stimulation (TBS) in rats showed complex effects on neuronal activity markers, with some markers increasing while others decreased, indicating that the response to TBS is not simply accumulative.

Specifically, while the expression of the vesicular glutamate transporter (VGLUT1) increased with stimulation, markers for inhibitory activity like GAD67 and calcium-binding proteins decreased, suggesting a nuanced interaction between excitatory and inhibitory neuronal responses to repeated TBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. Volz, LJ., Benali, A., Mix, A., et al.[2016]

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

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]

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]

Theta burst stimulation (TBS) shows promise in improving associative memory and enhancing functional connectivity in the hippocampus and other brain regions in individuals with mild cognitive impairment (MCI).

This study suggests that TBS can effectively target the hippocampus using functional MRI and diffusion-weighted MRI, although the findings are preliminary and based on a small sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffusion MRI-guided theta burst stimulation enhances memory and functional connectivity along the inferior longitudinal fasciculus in mild cognitive impairment. Chen, YC., Ton That, V., Ugonna, C., et al.[2022]

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

In a study involving 17 amyloid-positive participants with mild cognitive impairment (MCI) and 10 cognitively unimpaired controls, researchers found that LTP-like neuroplasticity was significantly impaired in those with MCI compared to controls, indicating early neuroplasticity issues in prodromal Alzheimer's disease.

Interestingly, a greater LTP-like response was associated with worse memory function in the MCI group, suggesting that neuroplasticity may play a complex role in the early stages of Alzheimer's disease and highlighting the potential of TMS as a tool for early diagnosis or treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LTP-like plasticity is impaired in amyloid-positive amnestic MCI but independent of PET-amyloid burden. Buss, SS., Press, DZ., McDonald, K., et al.[2021]

In a study involving 17 healthy older participants, there was a significant correlation between changes in motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex, indicating a relationship between corticospinal and cortical excitability.

While MEP amplitudes increased significantly after iTBS, TEP responses did not show significant changes, suggesting that the effects of iTBS on cortical activity (as measured by TEPs) are more complex and may not directly reflect changes in motor output.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects. Gedankien, T., Fried, PJ., Pascual-Leone, A., et al.[2019]

In a study involving 36 participants, it was found that the intensity of transcranial magnetic stimulation (TMS) significantly affects the plasticity response in the primary motor cortex, with higher intensities (150% of resting motor threshold) yielding greater depression effects from continuous theta burst stimulation (cTBS).

For intermittent theta burst stimulation (iTBS), the most effective probing intensity was at 110% of resting motor threshold, indicating that different intensities are crucial for accurately assessing neuroplasticity responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex. Goldsworthy, MR., Vallence, AM., Hodyl, NA., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03612622

Effect of Theta-Burst Transcranial Magnetic Stimulation ... Subjects must have a MMSE score between 10 and 27,indicating mild cognitive impairment or dementia; CDR score ≤ 2; Subject under treatment by IAChE for at ...

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. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1209205/full

Transcranial magnetic stimulation effects on cognitive ... Transcranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's ...

5. 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 ...

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

Efficacy and Safety of Transcranial Magnetic Stimulation on ... We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer disease (AD), AD-related dementias, and nondementia ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03612622

Effect of Theta-Burst Transcranial Magnetic Stimulation ... After the last treatment, the MoCA, and associative memory were obtained, as well as the Global Index of Safety to assess adverse events of the treatment.

8. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-025-01738-1

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

9. 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, ...