Redefining treatment for mild cognitive impairment

With more than $3.7 million in funding from the National Institute on Aging, Medical University of South Carolina neuropsychologist Andreana Benitez, Ph.D., of the Department of Neurology in the College of Medicine will lead a phase II clinical trial to determine the optimal dose of transcranial magnetic stimulation, or TMS, needed to improve symptoms for patients with depression and mild cognitive impairment, or MCI. In TMS, a magnet is placed against the patient’s head and stimulates the brain directly underneath.

Co-investigators include clinical neuropsychologist Stephanie Aghamoosa, Ph.D., of the College of Health Professions, as well as clinical psychologist Lisa McTeague, Ph.D., and psychiatrist and TMS pioneer Mark George, M.D., of the Brain Stimulation Lab within the Department of Psychiatry and Behavioral Sciences. George’s work helped TMS to gain approval from the Food and Drug Administration for the treatment of major depressive disorder in 2008.

In this study, the MUSC team will be using intermittent theta-burst TMS delivered in an accelerated treatment course: Participants will choose six TMS treatment days within a two-week period, each lasting about 2 ½ hours. Such an accelerated treatment course could be less burdensome for older adults with MCI.

What is MCI?

MCI is a diagnosis given to those in a predementia state. People with this diagnosis have more than the typical minor forgetfulness of aging but do not yet have the significant memory impairment seen with dementia.

“The clear distinction between MCI and dementia is that those with MCI are still able to be independent,” said Benitez. “They may need more time to complete complicated tasks, such as their taxes or finances, but these impairments shouldn’t be interfering with their everyday lives. This is certainly not the case with dementia.”

People with MCI are more likely to develop Alzheimer’s disease or other types of dementia. MCI can have many different causes, including Alzheimer’s disease and cerebrovascular diseases, such as stroke-like changes in the brain that are common in aging. Many people living with MCI also have depression, which can also be a risk factor for dementia. It is these people – those with MCI due to Alzheimer’s disease or cerebrovascular disease and depression – who will be invited to this study.

The researchers made a special effort to recruit people with MCI from various causes to represent the actual patient base seen clinically. The treatment under study has high potential for addressing various symptoms in a condition known to have varied causes.

Depression and MCI

Depression is common in the older population and especially in those with MCI. When applied to the front left side of the brain, TMS is already approved by the FDA for the treatment of major depressive disorder. The new MUSC study aims to find the optimal dose to improve both depression and thinking difficulties in MCI.

An accelerated treatment approach with a novel form of TMS

Intermittent theta burst, or iTBS, is a novel pattern of TMS: more stimulation pulses are being delivered in a shorter amount of time. Essentially, it’s a faster version of TMS. Instead of being administered for 20 to 30 minutes per session, as with traditional TMS, it is delivered in three minutes without losing efficacy.

“Despite this reduction in stimulation time, iTBS has been shown to improve depression as much as traditional TMS and is now FDA-approved for once-daily treatment of depression,” explained McTeague. “Because each treatment session is brief, we can deliver multiple sessions of TMS in a single treatment day, meaning that patients can complete in six treatment days what would typically require four to six weeks of once-daily treatment.”

In their earlier phase I trial, the researchers determined that this accelerated form of TMS was safe and well-tolerated by patients with MCI, due to either Alzheimer’s disease or stroke.

Finding the right dose

In this new phase II trial, the researchers hope to identify the dose of stimulation needed to improve depression and cognition in people with MCI.

“The big issue is that we don’t know how much stimulation people need to improve,” said Aghamoosa.

To identify the correct dose for each outcome, the researchers will conduct a dose-finding study.

“Some participants are going to be dosed with little to no stimulation all the way up to receiving all active treatment,” said Benitez. “We want to see how much we can improve memory and thinking and how much we can improve depression immediately after treatment as well as eight weeks and six months later.”

With additional funding provided to Aghamoosa by a discovery grant from the South Carolina Clinical & Translational Research Institute, the researchers will be able to track symptoms by providing Fitbits to participants who opt into this part of the study. Wearable technology, like Fitbits, gives researchers a better grasp on the daily habits of their research participants than does the traditional self-report method. Aghamoosa hopes to use the wearable technology to track how the accelerated treatment affects participants’ everyday activities.  

This study will be a critical first step in determining if accelerated TMS can help people with MCI and depression.

Once the researchers have identified the proper dose, their next step will be to conduct a multisite pivotal trial to test the efficacy of this treatment in a larger cohort of people with MCI.

“So far, brain stimulation methods like TMS are saving lives and having a big impact in patients with depression, but we have not yet figured out how to use TMS for MCI,” said George. “This study will answer important questions that will help us to use these tools to treat patients along the predementia to dementia spectrum.”

# # #

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About MUSC

Founded in 1824 in Charleston, MUSC is the state’s only comprehensive academic health system, with a unique mission to preserve and optimize human life in South Carolina through education, research and patient care. Each year, MUSC educates more than 3,200 students in six colleges – Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy – and trains more than 900 residents and fellows in its health system. MUSC brought in more than $298 million in research funds in fiscal year 2022, leading the state overall in research funding. MUSC also leads the state in federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.

As the health care system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest-quality and safest patient care while educating and training generations of outstanding health care providers and leaders to serve the people of South Carolina and beyond. Patient care is provided at 16 hospitals (includes owned and equity stake), with approximately 2,700 beds and four additional hospital locations in development; more than 350 telehealth sites and connectivity to patients’ homes; and nearly 750 care locations situated in all regions of South Carolina. In 2022, for the eighth consecutive year, U.S. News & World Report named MUSC Health University Medical Center in Charleston the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC has a total enterprise annual operating budget of $5.1 billion. The nearly 26,000 MUSC family members include world-class faculty, physicians, specialty providers, scientists, students, affiliates and care team members who deliver groundbreaking education, research, and patient care.

 

---

---