Motor and cognitive abilities in Parkinson’s disease with a brain activity perspective : performance at baseline and the effects of a balance training program

Background: Around one per cent of the population over 60 years of age have Parkinson’s disease (PD). PD is a progressive and complicated disease presenting a wide range of symptoms. More knowledge of the common impairments in balance, gait, cognition, and motor learning is needed. There is also a need for more studies of physical exercise as a complement to pharmacological treatment for people with PD. Our research group has previously observed positive effects of a highly challenging balance training program (HiBalance) for people with PD in comparison to a passive control group. It is of considerable interest to further investigate the effects of the HiBalance program using an enhanced design quality such as an active control group, blinded assessors as well as by the inclusion of measures of brain activity and neuroprotective factors (BDNF).

Aims: The first aim of this thesis was to develop feasible methods of investigating motor and cognitive abilities in people with PD as well as the effects of the HiBalance program. The second aim was to investigate motor and cognitive abilities as well as the effects of the HiBalance program for people with PD. This also included investigating the neural correlates of motor and cognitive baseline performances as well as the effects of the HiBalance program.

Methods: In Paper I, feasibility aspects relating to the recruitment process, measurement methods, and the participants’ experience of the assessments and the two interventions to be used in Paper IV were investigated. In Paper II, feasibility aspects of two computer-based tasks created to measure implicit motor sequence learning and dual-task ability were investigated. These tasks were to be used in Paper III and IV for task-induced functional magnetic resonance imaging data. Feasibility aspects investigated included task fatigue, difficulty level and possible ceiling effects. In Paper III, people with PD and healthy individuals performed the implicit motor sequence learning task during the acquisition of functional magnetic resonance imaging data. In Paper IV, we investigated a wide range of outcomes of the HiBalance program for people with mild to moderate PD. Our primary outcome was balance and secondary outcomes included gait speed, executive functions, and measures of brain activity during implicit motor sequence learning as well as measures of the brain-derived neurotrophic factor. We used a double-blinded randomised controlled design with an active control group.

Results: In Paper I, we found the feasibility of the randomised controlled design for investigating the HiBalance program to be overall acceptable but with some important modifications needed. In Paper II, we found the feasibility of the two computer-based tasks to be overall acceptable. In Paper III, we found support for the hypothesis that implicit motor sequence learning is impaired in people with PD. Exploratory analyses suggested that this impairment may be due to a lower learning rate. We found no statistically significant group changes in the task-induced brain activity. The results of Paper IV did not support the hypothesis of beneficial effects of the HiBalance program in comparison to our control group, for people with mild to moderate PD.

Discussion: The two feasibility studies guided us in design aspects that needed improvement before use in Paper III and Paper IV. We hope that our feasibility studies can also help other researchers in their study designs and thereby decrease unnecessary efforts for study participants and increase the value of research investments. As for paper III, impaired motor sequence learning in people with PD is an interesting finding as motor learning ability is of crucial importance for motor performance. If implicit motor sequence learning has a lower learning rate in people with PD than healthy individuals, this could mean that people with PD need more time to practice and repeat when learning and doing motor tasks and physical exercise. As for paper IV, the lack of support for the HiBalance program in its investigated form is discouraging. This is however an important finding that we hope will spark future rigorous projects aiming to find interventions of physical exercise with robust, replicable positive effects for people with PD.

List of scientific papers

I. Johansson, H., Freidle, M., Ekman, U., Schalling, E., Leavy, B., Svenningsson, P., Hagstromer, M., & Franzen, E. Feasibility Aspects of Exploring Exercise-Induced Neuroplasticity in Parkinson's Disease: A Pilot Randomized Controlled Trial. Parkinson’s Disease. 2020, 2410863.
https://doi.org/10.1155/2020/2410863

II. Freidle, M., Johansson, H., Lebedev, A. V., Ekman, U., Lövdén, M., & Franzen, E. Measuring implicit sequence learning and dual task ability in mild to moderate Parkinson's disease: A feasibility study. PloS One. 2021:16(5), e0251849.
https://doi.org/10.1371/journal.pone.0251849

III. Freidle, M., Thompson, W. H., Albrecht, F., & Franzén, E. Implicit motor sequence learning in people with mild to moderate Parkinson's disease: behaviour and related brain function. [Manuscript]

IV. Freidle, M.§, Johansson, H.§, Ekman, U., Lebedev, A. V., Schalling, E., Thompson, W. H., Svenningsson, P., Lövdén, M, Abney, A., Albrecht, F., Steurer, H., Leavy B., Holmin, S., Hagströmer, M., Franzén, E. Behavioural and neuroplastic effects of a double-blind randomised controlled balance exercise trial in people with Parkinson's disease. §Shared first authorship. [Submitted]