Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Interdisciplinary Neuroscience

Department

Interdisciplinary Neuroscience

First Advisor

Leslie Mahler

Abstract

Background and Purpose

The primary aim of this study was to investigate the impact of LSVT.BIG, an intensive, whole-body, amplitude-based exercise protocol for people with Parkinson’s disease (PwPD), on functional mobility, quality of life, and markers of neuroplasticity. A secondary aim was to evaluate correlations between neurobiological measures (serum brain derived neurotrophic factor - sBDNF) and functional changes associated with the intervention.

Methods

Nine people with Parkinson’s disease (PwPD), age = 69.9 years Å} 4.9, were recruited from the local community and enrolled in LSVT BIG, which includes 16, one-hour individual treatment sessions delivered over one month (4 sessions per week for 4 weeks). Dependent variables were measured at baseline (BASE), end of treatment (EOT), and 4 weeks after EOT (EOT+4). Mobility measures included stride length, gait speed, step length, functional gait assessment (FGA), MiniBEST Test, Timed Up and Go (TUG), and the MDS-UPDRS Part III Motor. Psychometric selfreport measures of fatigue, depression, confidence with activities, and Parkinson’s disease quality of life were also included. Cellular neuroplasticity was evaluated using changes in sBDNF.

Results

Statistically significant (a = .05) changes were identified in four of the six primary mobility variables at EOT+4 including the MDS-UPDRS Part III: Motor Examination, Functional Gait Assessment (FGA), MiniBEST balance, and step length but not in gait speed or the TUG. Participants made statistically significant changes at EOT and EOT+4 on the Activities-specific Balance Confidence (ABC) measure. No statistically significant changes were identified in measures of fatigue, depression, or health related quality of life measures. The sBDNF levels showed a 10.11% decline at EOT and an overall 30.94% decline from BASE to EOT+4, which was statistically significant but was weakly correlated with all mobility and psychometric variables.

Discussion and Conclusions

LSVT BIG is an effective behavioral treatment intervention for PwPD that can be implemented in a clinical setting for people experiencing mild to moderate disease severity. Improved function on several mobility variables, confidence with activities, and a positive impact on quality of life which was consistent with our first and second hypothesis. The strength of LSVT BIG may lie in its utilization of principles of neuroplasticity especially mode of delivery, saliency, intensity, frequency, and duration. Future research into the role each of these components may play will help guide future exercise prescription and open options for application of LSVT BIG to people with other neurologic diagnoses and beyond the population of PwPD.

A decline in sBDNF levels was significant but in contrast to the expected hypothesized increase in levels. There was an unexpected weak negative relationship with sBDNF across several variables. This decrease versus increase may be interpreted as a reflection of decreased disease load but requires further investigation and integration of additional neurotrophic factors to further expand our understanding of the role of sBDNF and its response to exercise.

This study provides insight into the potential benefits of a behavioral intervention that incorporates principles of motor learning that drive activity dependent changes in neural plasticity. Improvement in mobility measures were not statistically significant immediately following treatment but were significant four weeks following the completion of treatment. This finding may reflect that measurable changes in behavior occurred prior to changes in neural plasticity that is consistent with previous research (Adkins, Boychuk, Remple, & Kleim, 2006) and emphasizes the need for long term follow up for PwPD to fully understand the impact of exercise based treatment.

This study is unique in its integration of comprehensive functional, psychometric, and neurobiological measures in PwPD to broaden our understanding of the complex nature of exercise-induced neuroplasticity. These results further expand the limited body of research in the area of PD behavioral interventions and markers of neuroplasticity. In particular, this research has taken steps towards addressing the gap in treatment research by identifying specific measures regarding the efficacy of LSVT BIG, a well-defined treatment, as well as introduce the use of sBDNF as a potential link between functional neuroplasticity and cellular neuroplasticity.

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