Effects of Nordic Walking Exercise on Gait, Motor/Non-motor Symptoms, and Exercise Biomarkers in Parkinson's Disease

Overview

The purpose of this study is to examine the effects of Nordic pole walking exercise on walking function, movement and non-movement Parkinson-related symptoms, and certain exercise-related chemical indicators (bio-markers) in people with Parkinson's disease. This study will examine both the immediate and long-term effects of Nordic walking (NW) exercise on walking function, PD symptoms and exercise bio-markers after a supervised and individually progressed 6-week NW exercise training period and after a 3-month independent NW exercise phase. NW, as a task- specific exercise with higher energy demands than regular walking, has good practicality for independent walking exercise once the training program is completed. Therefore, this study will also examine independent NW exercise engagement after a supervised training program to assess feasibility and sustainability of this mode of task-specific aerobic exercise.

Parkinson's disease (PD) is a highly prevalent neuro-degenerative disorder in older adults that leads to reduced activity levels, physical disability, and accelerated age-related decline in mobility. Gait dysfunction and postural instability are key motor problems that develop with disease progression and adversely affect independent mobility, fall risk and activity participation. Prevention of balance, gait and functional decline are priority goals in physical therapy management for individuals with PD. Early activity-based and exercise interventions are supported as critical components for disease management and slowing disease progression. Furthermore, the underlying mechanisms by which exercise-based interventions effect changes in motor and non-motor symptoms in PD need to be further elucidated. Individualized aerobic exercise prescription that is task-specific, challenging, and feasible for an independent exercise program is needed for individuals with PD to optimize their walking and motor function and sustain long-term engagement in regular physical exercise. Walking as a form of aerobic exercise has been reported to be safe in a community setting and to improve functional and gait outcomes and quality of life in PD. Nordic walking (NW) is a form of fitness walking using specialty poles that mimics the full body movement pattern of cross-country skiing, can be performed in varied terrains and may offer additional benefits beyond simple treadmill or over ground walking. NW technique has specific benefits for Parkinson gait, as it incorporates rhythmic timing of inter-limb coordination, increased engagement of upper extremities and upright trunk, and high energy expenditure resulting in a beneficial aerobic conditioning effect. There is also consistent scientific evidence in both clinical and animal studies that shows the benefits of exercise at the cellular level in PD. Moderate to intense aerobic exercise enhances PD brain health and supports neural plasticity. Cellular changes include increased blood flow and angiogenesis, up-regulated neurotrophic factors, reduced neuro-inflammation, and enhanced immune responses. This project will evaluate the effects of NW in persons with PD at the molecular level with 3 known exercise-related bio-markers. These 3 bio-markers are brain-derived neurotropic factor (BDNF), cortisol, and alpha-amylase (α-amylase) proteins. Study objectives: Given the rapid accumulation of evidence showing the benefits of exercise in PD, there is a need to investigate which modes of exercise training have positive effects both on clinical measures and on bio-markers that are indicative of biochemical changes to support PD brain health. With a previously reported moderate aerobic conditioning effect following NW in both healthy elderly and PD cohorts, the premise is that this intensive fitness walking may produce changes at the cellular and molecular levels. Investigating changes in walking and motor/non-motor function following NW exercise and correlating these changes with exercise-related bio-markers may provide foundation support for the neuro-protective benefit of NW in persons with PD. Thus, the purpose of this proof-of concept study is to investigate the immediate and long-term effects of NW exercise on walking function, motor/non-motor PD symptoms and exercise-related bio-markers in persons with mild to moderate idiopathic PD. Additionally, this study will examine independent NW exercise engagement after a supervised training program to assess feasibility and sustainability of this mode of task-specific aerobic exercise. Study Design: This study will employ a prospective, single cohort pre- and post-intervention research design. Rationale for this design is twofold: 1. proof-of-concept in order to assess intervention effects based on functional and clinical measures following NW training and examine if these measures are associated with changes in exercise-related bio-markers in PD; and 2. assessment of feasibility of independent engagement in NW exercise after a supervised program in persons with mild to moderate PD as a mode of task-specific physical activity engagement. This research design will involve a 4-week baseline phase with two time points for assessment of dependent measures (T0-A and T0-B) to assess for a stable baseline, followed by a 6-week NW training intervention phase with a post-training assessment (T1) at the end of the 6 weeks, and a 3-month independent NW exercise phase with a follow-up assessment at the end of the 3 months (T2). Previous work in our lab has demonstrated significant improvements in walking and balance measures following a 6-week treadmill and rhythmic over ground auditory cuing protocols, and therefore, a 6-week training duration is expected to be sufficient for inducing training effects. Supervised NW adherence and independent NW exercise adherence, as well as any adverse effects will be monitored to determine feasibility and safety, particularly for independent NW phase of the study. Data Analysis: Descriptive statistics on patients' demographic characteristics (e.g. age, disease duration, stage, PD sub-type, fall history, activity level classification, medications and co-morbidity) will be documented. PD sub-type is categorized as tremor dominant, posture instability/gait difficulty, and indeterminate, based on MDS-UPDRS score. Descriptive statistics on patient's training sessions and training progression across the six weeks will be synthesized and analyzed. This training session data will include: training activities, walking speed, duration and distance of NW, Rating of Perceived Exertion, and walking terrain. Data from activity logs will be examined to reflect independent NW exercise adherence and activity level (number of steps/day) both during the 6-week training program and the follow-up independent exercise phase. Fall report data and any adverse events will be documented. This adherence and safety descriptive data during 3-month follow-up phase will reflect feasibility of independent home NW exercise program following a supervised NW training program. Descriptive statistics for the gait, clinical PD-motor and non-motor, and bio-marker outcome measures will be calculated. Comparison of the two-baseline gait and clinical measures (Baseline-week 1 T0-A vs baseline week 4 T0-B) will be analyzed using dependent t-tests to determine if there was a stable baseline for these dependent measures. If analysis reveals no differences between baseline measures, then T0-B will be used for comparison to T1 and T2 measures. If analysis reveals differences between baseline measures, then the average of the two measures will be used for comparison to T1 and T2 measures. Dependent measures distribution across the three time points (T0, T1, T2) will be analyzed to assess if meet the assumption of normal distributions. If the data are normally distributed, one-way repeated measures analysis of variance (ANOVA) with planned contrasts will be used for each outcome measure to compare baseline to T1, baseline to T2, and T1 to T2. ANOVA is a statistical method to test differences between two or more means (mean = average of a data set). A repeated measures ANOVA can be used to determine whether there is any statistically significant difference between the means of three or related groups (in this study, a related group is a specific time point). IF normality assumptions are not met, then the Friedman test with post hoc Wilcoxon sign-ranked pairwise comparisons will be used for each outcome measure to compare baseline to T1, baseline to T2, and T1 to T2 timepoints. Bonferroni correction was applied due to the number of analyses being conducted. Level of significance was set at 0.05. Repeated measures ANOVA will also be used to assess the changes in means over 8 collection time points in the BDNF, cortisol, and α-amylase data and show a time-course of the NW exercise effects in persons with PD. P value was set at p \<.05 for all statistical tests. To examine the magnitude of the training effects, the Cohen effect size will be calculated for those variables that demonstrated statistically significant change. Raw data of gene expression will be normalized and background corrected to set the data set to a common scale and remove the effects of non-specific binding across the micro arrays. The Limma package in R, a computational programming language for statistical computing and graphics will be used. Differential-expressed genes can then be identified to show gene expression changes that are statistically significant between different time points.