TMS for Mild Cognitive Impairment

(NetTMS Trial)

Overseen by Simon W Davis, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Duke University

Must not be taking: Seizure threshold, Memory affecting

Disqualifiers: Axis I disorder, Substance abuse, Seizures, Dementia, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses magnetic stimulation to target brain areas identified through MRI scans. It focuses on adults with mild cognitive impairment, aiming to improve memory by enhancing brain connectivity and function. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve cognitive function in patients with mild cognitive impairment (MCI).

Will I have to stop taking my current medications?

The trial requires that participants do not use medications known to lower the seizure threshold or affect working memory. If you are taking such medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment for mild cognitive impairment?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive symptoms in people with mild cognitive impairment by altering brain network connections. This approach has shown potential in enhancing cognitive performance in conditions related to Alzheimer's disease. ^{1 2 3 4 5}

Is TMS safe for humans?

Transcranial Magnetic Stimulation (TMS) has been studied in various conditions, including Alzheimer's disease and mild cognitive impairment, and is generally considered safe for humans. However, the specific safety profile can vary depending on the individual and the condition being treated, so it's important to discuss potential risks with a healthcare provider. ^{1 2 3 5 6}

How is the treatment Network-guided TMS different from other treatments for mild cognitive impairment?

Network-guided TMS is unique because it uses brain imaging to tailor the treatment to each individual's brain network, potentially improving its effectiveness by targeting specific areas affected by mild cognitive impairment. This personalized approach is different from traditional treatments that do not account for individual brain differences. ^{1 2 3 4 7}

Research Team

Simon W Davis, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for English-speaking adults aged 55-80 with mild cognitive impairment (MCI) who can consent to the study and are willing to use birth control if applicable. It's not for those with a history of substance abuse, pregnant or breastfeeding women, people with certain mental disorders, intracranial implants, pacemakers, seizure risks, significant head trauma or neurological conditions like dementia.

Inclusion Criteria

I am between 55 and 80 years old.

You have mild cognitive impairment as diagnosed by a doctor.

Use of effective method of birth control for women of childbearing capacity

Exclusion Criteria

You have a history of alcohol or drug addiction (except for nicotine).

I am not pregnant or breastfeeding.

I have a high risk of seizures due to conditions like epilepsy or serious head injury.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants complete neuropsychological tests and provide a saliva sample for APOE genotype determination

1 day

1 visit (in-person)

Initial MRI Scanning

Participants undergo an initial MRI scanning session to collect data for network-based targeting

1 day

1 visit (in-person)

Treatment

Participants undergo combined TMS-fMRI sessions to assess the effects of network-based TMS on memory performance

3 days

3 visits (in-person)

Follow-up

Participants are monitored for changes in neurovascular reactivity, structural connectivity, and episodic memory task performance

3 days

3 visits (in-person)

Treatment Details

Interventions

• Network-guided TMS (Neuromodulation)

Trial Overview The trial tests a new approach using transcranial magnetic stimulation (TMS), guided by MRI brain connectivity measures. The goal is to see if TMS can improve memory in older adults with MCI compared to fake (sham) treatment.

Participant Groups

Group I: Network-guided TMS Experimental Treatment 1 Intervention

The study comprises one arm of five sessions. In Day 1 (\~1.5 hr session), participants fill forms, complete a neuropsychological test battery (NIH Toolbox, NACC UDS, BDI), and provide a saliva sample to be banked for future APOE genotype determination. On Day 2 (\~1 hr session), subjects will perform an initial MRI scanning session. In this session, MRI, RSFA, DWI, and fMRI are collected so they can be used for network-based targeting. In Days 3-5 (each comprising a \~2.5 hr session) a few days later participants will undergo combined TMS-fMRI sessions. In the scanner, participants complete four fMRI runs: 2 runs using either a network-based or standard target location, counterbalanced across participants. Active and Sham TMS trials are intermixed within each run.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

This study demonstrates the feasibility of using individual resting-state fMRI to identify optimal TMS targets for Alzheimer's disease, focusing on the default mode and fronto-parietal networks, which are crucially affected in AD.

The individualized fMRI-guided TMS targeting approach showed significant differences in target localization compared to traditional methods, suggesting that personalized targeting could enhance the effectiveness of TMS treatments in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Imaging to Guide Network-Based TMS Treatments: Toward a Tailored Medicine Approach in Alzheimer's Disease. Bagattini, C., Brignani, D., Bonnì, S., et al.[2021]

Neuro-navigated rTMS applied to the left angular gyrus significantly improved cognitive performance in patients with amnestic mild cognitive impairment and Alzheimer's disease, indicating its potential as a therapeutic intervention.

The study found that changes in brain network connectivity, particularly in higher-order cognitive networks, could predict individual responses to rTMS treatment, suggesting a personalized approach to therapy based on baseline brain dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional network connectivity patterns predicting the efficacy of repetitive transcranial magnetic stimulation in the spectrum of Alzheimer's disease. Chen, H., Li, M., Qin, Z., et al.[2023]

Transcranial magnetic stimulation (TMS) can effectively differentiate between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults by measuring cortical excitability and plasticity, with 2728 participants analyzed across 61 studies.

The study found that patients with AD had higher cortical excitability and lower inhibition compared to cognitively normal individuals, with no reported seizure events from TMS, indicating its safety as a diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies. Chou, YH., Sundman, M., Ton That, V., et al.[2022]

In a study of 40 patients with amnestic mild cognitive impairment (aMCI), it was found that they exhibited lower cortical excitability and altered synaptic plasticity compared to healthy controls, as measured by 5 Hz repetitive transcranial magnetic stimulation (5 Hz-rTMS).

The study revealed that specific TMS parameters, such as the resting motor threshold and the ratio of the first to the tenth motor-evoked potential, correlated with the time it took for patients to convert to Alzheimer's disease, suggesting these measures could serve as early neurophysiological markers for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer's Disease: Results from a 4-year Prospective Cohort Study. Trebbastoni, A., Pichiorri, F., D'Antonio, F., et al.[2023]

In a study involving 11 patients with mild-to-moderate Alzheimer's disease, chronic treatment with rivastigmine increased the amplitude of motor evoked potentials (MEP) after a single stimulus, indicating some improvement in cortical excitability.

However, rivastigmine did not affect short-term synaptic plasticity or the normal facilitation of MEP during repetitive transcranial magnetic stimulation (rTMS), suggesting that the limited clinical benefits of cholinesterase inhibitors in Alzheimer's may not be due to enhanced cortical plasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation. Trebbastoni, A., Gilio, F., D'Antonio, F., et al.[2015]

This study introduces a novel network-based model for optimizing TMS (transcranial magnetic stimulation) treatment by targeting disease-specific brain networks, which could enhance treatment outcomes for conditions like depression and schizophrenia.

The model was validated using empirical data from two depression cohorts and one schizophrenia cohort, suggesting that individualized coil placement based on the patient's specific brain network abnormalities may lead to improved therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the pathological network: Feasibility of network-based optimization of transcranial magnetic stimulation coil placement for treatment of psychiatric disorders. Cao, Z., Xiao, X., Zhao, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Functional Imaging to Guide Network-Based TMS Treatments: Toward a Tailored Medicine Approach in Alzheimer's Disease. [2021]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Functional network connectivity patterns predicting the efficacy of repetitive transcranial magnetic stimulation in the spectrum of Alzheimer's disease. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer's Disease: Results from a 4-year Prospective Cohort Study. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting the pathological network: Feasibility of network-based optimization of transcranial magnetic stimulation coil placement for treatment of psychiatric disorders. [2023]