Mild Cognitive ImpairmentNetTMSNCT04549155
Network-guided TMS in Early Alzheimer's Disease
A study testing Transcranial Magnetic Stimulation in people with Mild Cognitive Impairment, run by Duke University at 1 site in United States.
Trial summary
The proposed research will test a novel network-based neurostimulation approach using MRI-derived measures of brain connectivity to establish target sites for neurostimulation and test for the enhancement of memory function beyond a sham stimulation condition. Read more about this study
- Who is it for?
- Ages 60 to 82 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2022to 27 Jun 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 82 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Elderly: age between 60-82
- English speaking
- Willing to provide consent
- Signed HIPAA authorization
- Use of effective method of birth control for women of childbearing capacity
- Clinical Consensus for MCI
Who cannot join
- History of any Axis I DSM-IV disorder
- Current or past history of substance abuse or dependence (excluding nicotine)
- Women who are pregnant or breast feeding
- Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes), cardiac pacemakers, or vagus Nerve stimulation device
- Increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma with loss of consciousness for ≥ 30 minutes.
- Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; fainting, cerebral aneurysm,
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- Dementia, Hungtington chorea; Multiple Sclerosis.
- Current use of medications known to lower the seizure threshold and/or affect working memory
- Current or past history of substance abuse or dependence (excluding nicotine)
- Women who are pregnant or breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Using Network-guided TMS to Ameliorate Memory Deficits in Early Alzheimer's Disease
The proposed research will test a novel network-based neurostimulation approach using MRI-derived measures of brain connectivity to establish target sites for neurostimulation and test for the enhancement of memory function beyond a sham stimulation condition. This will be tested in cohort of MCI adults using network-based transcranial magnetic stimulation (TMS) to assess for behavioral improvement due to the controlled intervention. This study will provide important evidence towards the efficacy of neuromodulatory treatments for memory decline and will accelerate the discovery of potent non-invasive treatments to remediate cognitive decline in cognitively impaired older adults.
Read the detailed description
Dementia due to Alzheimer's disease (AD) is a leading public health concern in the US with tremendous care costs and no effective pharmacotherapy despite multiple clinical trials. Numerous studies have shown mild cognitive impairment (MCI) to be a precursor to AD and potentially amenable to nonpharmacological intervention. Transcranial magnetic stimulation (TMS) is a promising non-invasive therapeutic approach that has been shown to increase brain plasticity and enhance cognitive functions that are impaired across the AD spectrum. Yet, while TMS has shown benefits in normative populations, there is still a need to show efficacy in AD-related populations.
Most previous neurostimulation research on AD and MCI has focused on effects of stimulation at one brain region, however the cognitive processes underlying successful memory are mediated by a complex whole-brain network. Neurostimulation affects multiple sites within a cortical network, but these more global effects have not been used as targets for stimulation because of limited knowledge about what influence of a single site on more widespread cortical changes. The novelty of the current proposal is that the investigators use information about the network control structure of the affected brain areas by considering the influence of neuromodulation on global changes in brain state or connectivity and the underlying vascular changes mediating long-term consequences for behavior. This network-based TMS is informed by functional connectivity and neurovascular as mediators of the behavioral response as a means to specifically tailor the TMS treatment to the neuropathology of each MCI patient, thus individualizing the treatment to achieve better therapeutic effects.
To address this problem, the investigators will use multimodal neuroimaging and network modeling during an episodic memory task to demonstrate how focal neurostimulation evokes changes in neural function and behavior in MCI. These goals will be addressed in two specific aims. First, the investigators will use network-based TMS to optimize the activation of a memory success network (MSN) in a group of MCI patients, targeting a TMS site that focused on the controllability of a stimulation site to provide the maximum benefit to memory performance. Second, the study team will assess longitudinal change in structural and neurovascular factors affecting the efficacy of individualized network-based TMS across multiple sessions of concurrent TMS-fMRI. By creating a multimodal model of these neurovascular deficits related to MCI, the investigators will systematically adjust network-based TMS to demonstrate how the MCI brain might compensate for these neural deficits. The proposed work will be the first of its kind to estimate the utility of network controllability as a TMS target for memory enhancement in AD-related syndromes, and the first to assess the short-term neuroplastic effects of neuromodulation in such rich detail. The knowledge gained by this project may therefore lead to novel and innovative biometrics for gauging pharmacological and nonpharmacological treatment response or for targeted and enriched clinical trials in AD and related disorders.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Transcranial Magnetic Stimulation
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS, rTMS
Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve a variety of cognitive conditions, and to probe the dynamics of normal brain function.
| Study group | Role | What they receive |
|---|---|---|
| Network-guided TMS | Experimental | 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. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Episodic Memory Task Performance
The primary outcome measure is the difference in memory accuracy between TMS conditions (active vs. sham) on an episodic memory task. Participants perform the Episodic Memory task after active network-guided or sham TMS. During each block of the Encoding phase, participants view a series of real-world objects and perform a relatedness judgement. During the Retrieval phase (post-scan), participants perform a recognition memory task including a mix of old objects and new objects, and memory is then subsequently assessed as a function of TMS condition. Reported as a hit rate, calculated by dividing the number of correct responses by the number of presented tasks.
Measured: Baseline + Follow-up session, at day 3
Change in Representational Strength of Episodic Memories
The primary outcome measure is the difference in Representational Strength between TMS conditions (active vs. sham) during the episodic encoding task, at the site of TMS stimulation (Lateral Parietal Cortex). Participants perform the Episodic Memory task after active network-guided or sham TMS. During each block of the Encoding phase, participants view a series of real-world objects and perform a relatedness judgement. Representational strength reflects the degree to which participants use semantic or perceptual information during encoding. Representational strength is calculated by comparing the similarity in activation patterns in a given brain region with the similarity in model estimates (semantic model: overlap of semantic features; perceptual model: overlap of perceptual features. As such, this measure reflects a Pearson's correlation (between -1 and 1) between brain and model similarity measures.
Measured: Baseline + Follow-up session, at day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start8 Mar 2022
- Primary completion27 Jun 2025
- Study completion27 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study has two Aims, and thus two models. For Aim 1, the primary outcome measure is the difference in memory accuracy between TMS conditions, based on a mixed-effects design consisting of 4 repeated measurements per subject (2 memory conditions \[successful, unsuccessful\] x 2 TMS targeting \[network-based, standard\]). For Aim 2, the primary outcome measure comprises longitudinal changes in both memory performance, as well as brain imaging measures of functional and structural connectivity, and neurovascular change. For the behavioral estimates, we analyze the TMS Condition x Session interaction, which comprised 4 sessions of TMS with longitudinal estimates of behavior in 30 older adults.
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Andrew Liu, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549155
- Sponsor's protocol ID
- Pro00106545
- Acronym
- NetTMS
- Status last verified
- Oct 2026
- First submitted
- 9 Sep 2020
- Last updated
- 27 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Network-guided TMS to Ameliorate Memory Deficits in Early Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04549155
- Acronym / sponsor ID
- NetTMS / Pro00106545
- Conditions
- Mild Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 27 Jun 2025 (actual)
- Study completion
- 27 Jun 2025 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Posted 27 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed research will test a novel network-based neurostimulation approach using MRI-derived measures of brain connectivity to establish target sites for neurostimulation and test for the enhancement of memory function beyond a sham stimulation condition. This will be tested in cohort of MCI adults using network-based transcranial magnetic stimulation (TMS) to assess for behavioral improvement due to the controlled intervention. This study will provide important evidence towards the efficacy of neuromodulatory treatments for memory decline and will accelerate the discovery of potent non-invasive treatments to remediate cognitive decline in cognitively impaired older adults.
Detailed description
Dementia due to Alzheimer's disease (AD) is a leading public health concern in the US with tremendous care costs and no effective pharmacotherapy despite multiple clinical trials. Numerous studies have shown mild cognitive impairment (MCI) to be a precursor to AD and potentially amenable to nonpharmacological intervention. Transcranial magnetic stimulation (TMS) is a promising non-invasive therapeutic approach that has been shown to increase brain plasticity and enhance cognitive functions that are impaired across the AD spectrum. Yet, while TMS has shown benefits in normative populations, there is still a need to show efficacy in AD-related populations.
Most previous neurostimulation research on AD and MCI has focused on effects of stimulation at one brain region, however the cognitive processes underlying successful memory are mediated by a complex whole-brain network. Neurostimulation affects multiple sites within a cortical network, but these more global effects have not been used as targets for stimulation because of limited knowledge about what influence of a single site on more widespread cortical changes. The novelty of the current proposal is that the investigators use information about the network control structure of the affected brain areas by considering the influence of neuromodulation on global changes in brain state or connectivity and the underlying vascular changes mediating long-term consequences for behavior. This network-based TMS is informed by functional connectivity and neurovascular as mediators of the behavioral response as a means to specifically tailor the TMS treatment to the neuropathology of each MCI patient, thus individualizing the treatment to achieve better therapeutic effects.
To address this problem, the investigators will use multimodal neuroimaging and network modeling during an episodic memory task to demonstrate how focal neurostimulation evokes changes in neural function and behavior in MCI. These goals will be addressed in two specific aims. First, the investigators will use network-based TMS to optimize the activation of a memory success network (MSN) in a group of MCI patients, targeting a TMS site that focused on the controllability of a stimulation site to provide the maximum benefit to memory performance. Second, the study team will assess longitudinal change in structural and neurovascular factors affecting the efficacy of individualized network-based TMS across multiple sessions of concurrent TMS-fMRI. By creating a multimodal model of these neurovascular deficits related to MCI, the investigators will systematically adjust network-based TMS to demonstrate how the MCI brain might compensate for these neural deficits. The proposed work will be the first of its kind to estimate the utility of network controllability as a TMS target for memory enhancement in AD-related syndromes, and the first to assess the short-term neuroplastic effects of neuromodulation in such rich detail. The knowledge gained by this project may therefore lead to novel and innovative biometrics for gauging pharmacological and nonpharmacological treatment response or for targeted and enriched clinical trials in AD and related disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study has two Aims, and thus two models. For Aim 1, the primary outcome measure is the difference in memory accuracy between TMS conditions, based on a mixed-effects design consisting of 4 repeated measurements per subject (2 memory conditions [successful, unsuccessful] x 2 TMS targeting [network-based, standard]). For Aim 2, the primary outcome measure comprises longitudinal changes in both memory performance, as well as brain imaging measures of functional and structural connectivity, and neurovascular change. For the behavioral estimates, we analyze the TMS Condition x Session interaction, which comprised 4 sessions of TMS with longitudinal estimates of behavior in 30 older adults.
| Arm | Type | Receives |
|---|---|---|
| Network-guided TMS | Experimental | Device: Transcranial Magnetic StimulationThe 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 may qualify
- Ages
- 60 to 82 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Elderly: age between 60-82
- English speaking
- Willing to provide consent
- Signed HIPAA authorization
- Use of effective method of birth control for women of childbearing capacity
Key exclusion criteria (10 listed)
- History of any Axis I DSM-IV disorder
- Current or past history of substance abuse or dependence (excluding nicotine)
- Women who are pregnant or breast feeding
- Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes), cardiac pacemakers, or vagus Nerve stimulation device
- Increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma with loss of consciousness for ≥ 30 minutes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationAlso: TMS, rTMSTranscranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve a variety of cognitive conditions, and to probe the dynamics of normal brain function. | Device | Network-guided TMS |
Primary outcome
Episodic Memory Task Performance
Time frame: Baseline + Follow-up session, at day 3
The primary outcome measure is the difference in memory accuracy between TMS conditions (active vs. sham) on an episodic memory task. Participants perform the Episodic Memory task after active network-guided or sham TMS. During each block of the Encoding phase, participants view a series of real-world objects and perform a relatedness judgement. During the Retrieval phase (post-scan), participants perform a recognition memory task including a mix of old objects and new objects, and memory is then subsequently assessed as a function of TMS condition. Reported as a hit rate, calculated by dividing the number of correct responses by the number of presented tasks.
Change in Representational Strength of Episodic Memories
Time frame: Baseline + Follow-up session, at day 3
The primary outcome measure is the difference in Representational Strength between TMS conditions (active vs. sham) during the episodic encoding task, at the site of TMS stimulation (Lateral Parietal Cortex). Participants perform the Episodic Memory task after active network-guided or sham TMS. During each block of the Encoding phase, participants view a series of real-world objects and perform a relatedness judgement. Representational strength reflects the degree to which participants use semantic or perceptual information during encoding. Representational strength is calculated by comparing the similarity in activation patterns in a given brain region with the similarity in model estimates (semantic model: overlap of semantic features; perceptual model: overlap of perceptual features. As such, this measure reflects a Pearson's correlation (between -1 and 1) between brain and model similarity measures.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Liu, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Mild Cognitive Impairment, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Episodic Memory Task Performance (time frame: Baseline + Follow-up session, at day 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.