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. 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."
Andreana Benitez, Ph.D., Department of Neurology, College of Medicine, MUSC
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."