Pilot Study Supports Larger Trial on Exercise and Brain Health in Parkinson’s

A pilot study in Sweden shows the feasibility of testing how exercise benefits neuroplasticity — the brain’s ability to adjust and make new connections in response to stimuli or damage — in people with Parkinson’s disease, making a larger and more scientifically rigorous clinical trial possible.

An ability to replicate on a larger scale previous studies of exercise on brain health in these patients has been lacking, its researchers noted.

The pilot trial was described in “Feasibility Aspects of Exploring Exercise-Induced Neuroplasticity in Parkinson’s Disease: A Pilot Randomized Controlled Trial,” published in the journal Parkinson’s Disease.

It is well-established that exercise can be beneficial for Parkinson’s patients, helping to improve balance and coordination. These benefits may be tied to physical changes within the brain, and understanding exactly how could be important for best managing PD.

“If these improvements in behavior can be specifically linked to brain plasticity,” the researchers wrote, “this knowledge could guide clinicians when choosing and progressing programs that are conducive to more enduring changes.”

While some studies have tried to define these changes, many were non-randomized and too small for firm conclusions to be drawn. In theory, these studies could be repeated, with more participants, to gather better data. However, their often complex designs are difficult to translate to a larger and more varied Parkinson’s group.

The pilot study, by researchers with the Karolinska Institutet, involved  13 people with mild to moderate Parkinson’s. Its goal was to assess the feasibility of the design for use in a larger and planned trial, and to highlight areas where improvements could be made before moving to that larger scale.

Feasibility goals included making sure that enough people could be recruited (based on interest and eligibility), making sure participants were able to stick to the exercise intervention, and confirming that data could be collected appropriately.

BETA-PD, as this follow-up trial is known (NCT03213873), took place at the institute in Stockholm and could enroll up to 96 patients also with mild to moderate disease. It concluded in December, and its results are not part of this published study.

The specific intervention assessed in both trial is called HiBalance, and reported to be beneficial in Parkinson’s disease. It consists of exercises that target core areas of balance control that are often hindered in people with PD.

Half of the participants in the pilot trial were randomized to a HiBalance program consisting of two hour-long sessions, twice per week. The other half were randomized to an equal amount of speech and communication therapy. (Randomization to either of these same groups — HiBalance or speech/communication therapy — was used in the larger trial as well.)

This speech group served as the control — the idea behind having them participate in a different type of therapy is to test the effect of variables apart from exercise, such as increased social interaction, that could impact the results.

Both groups were also instructed to participate in home-based exercises programs, which for the HiBalance group involved doing aerobic/strength exercises, or for the other group involved speech exercises.

Participants underwent tests measuring physical ability, cognitive function, and well-being. Magnetic resonance imaging (MRI) brain scans were also taken.

These scans posed a number of unanticipated obstacles, researchers reported, including patients falling asleep while in the machine and being unable to undergo an MRI because of concerns that weren’t disclosed until the last minute.

“All in all, only four participants allocated to the HiBalance group and three participants in the control group had acceptable behavioral data at the pretesting session,” the researchers wrote. Because of this, “it was not deemed sensible to make any analyses of the data but very basic quality assessments.”

There were also problems with the dual-gait assessment — a paradigm where a person is assessed while they try to do two tasks simultaneously. In this case, patients were asked to do a word puzzle while walking. Many earned perfect scores from the beginning, making it impossible to identify improvements.

Another problem had to do with blinding. Since human bias can affect outcomes, studies are usually conducted so that investigators are not aware of what treatment the person they are evaluating has been receiving. But assessors in the pilot study were often able to correctly guess which treatment participants were given, indicating a need for better blinding procedures to minimize bias in the larger trial.

Beyond these issues, this study design was deemed feasible for use in the larger study.

“Attendance rates and follow-up questionnaires suggest that both the HiBalance intervention and control group intervention were acceptable to participants. The low number of adverse events further indicates that both interventions are safe for the definitive trial,” the researchers wrote.

Although the trial was not designed to assess treatment responses, measures were taken for both groups of physical performance, well-being, cognitive function, and voice intensity.

Balance performance showed no trends toward effect in either group. However gait speed showed a tendency to increase and health-related quality of life showed positive trends in the HiBalance group compared to the control group.

Some results of executive function test also favored the HiBalance group, while others favored the control group. People in both groups seemed to show better cognitive flexibility.

“Voice intensity measures showed that control group participants improved, while the HiBalance group did not which indicates that the components of the control group were active for the intervention-targeted behavior,” the researchers wrote.

Still, the small number of participants “makes it difficult to draw firm conclusions.”

“Overall, the different elements of the design were feasible,” they concluded. “However, ahead of the definitive trial, we recommend modifications specifically with respect to blinding procedures and expectancy as well to the MRI paradigm and the dual-task gait assessment.”