Trial tests cognitive rehab with VR-based exercise to boost memory
Researchers expect combination will stimulate learning in MS patients
A clinical trial is evaluating whether combining a cognitive rehabilitation program with a virtual reality (VR)-based aerobic exercise regimen will improve learning and memory in people with multiple sclerosis (MS) and motor disability.
Researchers expect the approach will show cognitive benefits via positive effects on a brain region called the hippocampus. The COMBINE trial (NCT06197685) will involve 78 adults with MS and mobility problems, ages 18-70, at a single site in New Jersey.
The design and rationale for the trial were described in a paper, “Rationale and methodology for examining the combination of aerobic exercise and cognitive rehabilitation on new learning and memory in persons with multiple sclerosis and mobility disability: Protocol for a randomized controlled trial,” published in Contemporary Clinical Trials.
“This trial is a significant step forward in our understanding of how multimodal interventions can enhance cognitive outcomes for people with MS,” Carly Wender, PhD, a researcher at the Kessler Foundation and the paper’s first author, said in a foundation press release. “Combining exercise with cognitive rehabilitation has the potential to produce synergistic effects, particularly in individuals with greater disease progression,” said Wender, who is also a COMBINE investigator.
Cognitive rehab thought to stimulate hippocampus
Cognitive impairment is a common symptom of MS that can reduce independence and quality of life for patients, especially when they also have substantial motor disabilities.
MS patients sometimes struggle with new learning and memory. This has been linked to a loss of tissue or dysfunction in the hippocampus, a brain region important for memory.
The KF-modified Story Memory Technique (KF-mSMT) is a cognitive rehabilitation strategy designed by Kessler Foundation researchers. It aims to improve a person’s ability to memorize a list of words by pairing them with imagery and context.
Previous studies have indicated that this approach activates the hippocampus and can moderately improve MS patients’ list-learning ability. Since the cognitive impairments observed in MS patients extend beyond list-learning, there is a need for more robust rehabilitation approaches, according to the researchers.
Recent work from Wender and colleagues has suggested that aerobic exercise can have benefits for learning and memory in MS, potentially by promoting nerve cell growth and increasing the size of the hippocampus.
It’s thought that increasing the sensory input to the brain during exercise results in greater cognitive improvements. The researchers hypothesized that adding a VR component to exercise could further enhance its cognitive benefits in MS.
The COMBINE trial is designed to test the effects of combining KF-mSMT with a VR-based aerobic exercise training program. The study aims to enroll MS patients who have moderate self-reported mobility disability and are physically inactive. Eligible participants will also have new learning and memory deficits.
Participants will receive either KF-mSMT with a VR-based aerobic exercise routine or KF-mSMT with stretching (a control group) for 12 weeks, or about three months.
Cognitive rehab with cycling, stretching
The VR-based exercise program involves supervised, moderate-intensity workouts on a stationary bike. During the cycling, a large, curved monitor will be placed in front of the bike, which will project a semi-immersive VR environment of the participant’s choosing. The stretching program will involve supervised stretching exercises targeting muscles throughout the body.
For the first seven weeks, participants will perform only their prescribed exercise regimen three days per week. In the last five weeks, KF-mSMT will be performed after the exercise regimen on two of those days.
The study’s main goal is to evaluate the effects of the combined program on various aspects of new learning and memory, including list learning, visuospatial memory, and everyday memory. Changes in the volume and function of the hippocampus, assessed via magnetic resonance imaging, will be assessed as secondary trial goals.
Researchers expect that cognitive rehab will have better effects on various aspects of new learning and memory when combined with VR-based exercise, and that this will be accompanied by increases in the volume of the hippocampus.
“By targeting the hippocampus through both cognitive and physical stimuli, we aim to provide more effective treatment options for individuals who face substantial cognitive challenges due to MS,” Wender said.
Should the scientists observe the benefits they’re expecting, future research will look more carefully at the best way to implement such a program and determine which patients benefit the most.
If proven effective and optimized, the program “can be implemented in clinical care to directly improve the lives of persons with MS, mobility disability, and objective cognitive impairment,” the researchers wrote.
The COMBINE study is supported by a grant from the National Multiple Sclerosis Society.
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