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Completed

NCT Number: NCT03962959

Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

The ultimate goal of this study is to develop non-invasive, painless repetitive transcranial magnetic stimulation (rTMS) protocols to prevent cognitive decline in patients with mild cognitive impairment (MCI) and cognitively normal individuals at high risk of developing Alzheimer's disease (AD). Currently, 1 in 9 adults over the age of 65 have AD, which currently totals more than 5 million Americans and this number is expected to rise as high as 16 million by 2050.

MCI is a clinical syndrome that represents the gray area between healthy aging and dementia. Those with amnestic MCI (aMCI) have memory problems more severe than normal for their age and education, but their symptoms are not as severe as those of people with AD. Patients with aMCI are at high risk for AD. Notably, roughly half of those with MCI will continue to progress and convert to clinical dementia within 3 years. Alternatively, it is also worthwhile to study cognitively healthy older adults who carry genes that may increase the risk of AD. The frequency of the human APOE gene ε4 allele increases in patients with AD and the ε4 allele is also associated with an earlier age of disease onset.

Currently, there are no known therapies that can effectively modify the progression and hallmark symptoms of AD. Therefore, it is crucial to provide an early intervention in patients with aMCI to delay or prevent the progression to AD.

More specifically, this project has two specific aims:

1. To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI) 2. To identify potential personalized cognitive enhancement strategy (such as dosage or patterns) of Transcranial Magnetic Stimulation (TMS) in MCI.

Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals and people with clinical conditions. With these practices, researchers can safely stimulate specific regions of the brain to explore causal relationships that comprise the brain's circuitry and modulate behavior.

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Key information

Conditions

Mild Cognitive Impairment Cognition Disorders Cognitive Dysfunction Mental Disorders Neurocognitive Disorders

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Bioscience Research Laboratory

Tucson, Arizona, 85719, United States

About this study

In total, 60 participants (50-85 years old) with MCI will be recruited to participate in this trial.

Participants will be asked to receive 30 intervention sessions for three different protocols (10 sessions for each). Before and after the interventions, MRI and Cognitive tasks will be utilized again as the outcome measurements. There is a one-month interval between each protocol. Each intervention will be around half hour to an hour and each outcome measurement will take another two hours.

Each block includes:

  • MRI+ Memory pre-assessment (2 hours/session)
  • TMS * 10 (10 sessions; 0.5 hours/session)
  • MRI+ Memory post-assessment (2 hours/session) Participants will experience each of the three TMS protocols. The total time commitment across these sessions will be approximately 27 hours.

There will be another 2 testing sessions to evaluate intervention effects. They will be scheduled at the beginning, and 1 month after the end of the intervention sessions. All sessions will take place in the Biosciences Research Laboratories (BSLR) Building (1230 N. Cherry Ave., Tucson, AZ 85721). The schematic below outlines the components of the sessions.

The investigators will acquire the following data during components for primary outcome measures and secondary measures.

  • Brain imaging data 2) Neuropsychological data and demographic data 3) Cognitive tasks 4) Biological sample

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Individuals with mild cognitive impairment (MCI Group)

Inclusion criteria

  • Age 50-85 years
  • MCI clinical criteria: (a) typical comprehensive criteria (at least one cognitive test <= -1.5 SD), or (b) Jak/Bondi criteria (2 tests within the same domain <= -1SD or 3 tests total <= -1SD)
  • Right handed
  • English speaking
  • Able to attend daily intervention (Monday-Friday) for 4 weeks
  • Not enrolled in another interventional study within 6 months prior to beginning this study

Exclusion criteria

  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Current cancer treatment or other medical problems that might independently affect cognitive function

Cognitively Normal Individuals:

Inclusion criteria

  • Age 50-85 years
  • Right handed
  • English speaking
  • Able to attend daily intervention (Monday-Friday) for 4 weeks
  • Not enrolled in another interventional study within 6 months prior to beginning this study

Exclusion criteria

  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • No dementia or impaired cognitive functioning, assessed using the NACC battery.

Treatment and study plan

TBS

Device

TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.

Other names: Theta Burst Stimulation (TBS)

Primary outcomes

  1. Brain imaging data

    Time frame: Baseline

    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. NACC Neuropsychological batteries

    Time frame: Baseline

    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  3. Correction rate in memory association recall

    Time frame: Baseline

    Memory tasks will be implemented and measure the correct rate to assess memory function.

  4. Specimen sample

    Time frame: 1 day (Only once in the beginning phase)

    A specimen for DNA will be collected and determine whether participants have APOE genotype.

Secondary outcomes

  1. Brain imaging data

    Time frame: 2 weeks after the intervention phase begin

    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. Correction rate in memory association recall

    Time frame: 2 weeks after the intervention phase begin

    Memory tasks will be implemented and measure the correct rate to assess memory function.

Other outcomes

  1. Brain imaging data

    Time frame: an average of 1 month

    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. Brain imaging data

    Time frame: 3 months after the intervention phase complete

    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  3. NACC Neuropsychological batteries

    Time frame: an average of 1 month

    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions function. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  4. NACC Neuropsychological batteries

    Time frame: 3 months after the intervention phase complete

    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  5. Correction rate in memory association recall

    Time frame: an average of 1 month

    Memory tasks will be implemented and measure the correct rate to assess memory function.

  6. Correction rate in memory association recall

    Time frame: 3 months after the intervention phase complete

    Memory tasks will be implemented and measure the correct rate to assess memory function.

Sponsors and collaborators

Lead sponsor

University of Arizona

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
May 24, 2019
Registry last updated
Apr 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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