High-Intensity Interval Cycle Ergometer Training in Parkinson's Disease: Protocol for Identifying Individual Response Patterns Using a Single-Subject Research Design

Abstract

Background: People with Parkinson's disease (PD) experience not only motor problems but also non-motor problems that seriously impede their daily functioning and quality of life. The current pharmacologic treatment of PD is symptomatic, and alternative rehabilitation treatments, which preferably also have a disease-modifying effect and promote neuroplasticity, are needed. Recent studies suggest that high-intensity interval training (HIIT) is promising for promoting neuroplasticity in human PD, with short training time and reduced burden. Biomarkers for neuroplasticity such as brain-derived neurotrophic factor (BDNF) and neurodegeneration (including neurofilament NfL and α-synuclein) may play a role, but their response to HIIT is not well-investigated. Objectives: The aims of this study were (1) to study the effects of 4 weeks of HIIT compared with 4 weeks of continuous aerobic exercise on motor and non-motor outcomes of PD and (2) to investigate the association between HIIT, motor/non-motor performances changes, and blood biomarker levels for neuroplasticity and neurodegeneration. Study Design: Single-subject research design with alternating treatment setup (ABACA) and frequent repeated measurements was used. Each participant received different intervention conditions (B/C) interspersed with baseline periods (A, i.e., ABACA or ACABA), and frequent repeated assessment of outcome measures is done to quantify within-subject, individual response patterns with sufficient power for data analysis. Blood samples were collected once a week in the baseline and training phases (A1 and B/C) and once every 2 weeks in the washout phases (A2 and A3). van Wegen et al. HIIT in Parkinson's Disease Intervention: Four subjects with PD on stable dopaminergic medication, two in Hoehn-Yahr stage 1-2, and two in Hoehn-Yahr stage 2.5-3 followed an ABACA or ACABA schedule, consisting of blocks with 30-min sessions of "B" (HIIT) or 50-min sessions of "C" [continuous aerobic exercise (CAE)] 3×/week for 4 weeks, separated by baseline "A" periods of 8 weeks for a total duration of 28 weeks. Outcome Measures: Outcome measures include disease status [Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], blood biomarkers (BDNF, Nfl, and α-synuclein), measures for functional mobility (including an activity tracker), and activities of daily living, as well as cognition, mood, biorhythm (sleeping problems), and quality of life. Data Analysis: Visual analysis of trends in level, slope, and variability in response patterns was carried out, confirmed by longitudinal regression analysis with phase (ABACA) as the independent variable.

Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats

“…HIIT is being used in human aging studies, (over 139 citations in PubMed) and most notably regarding age-related diseases, especially Parkinson's (39)(40)(41). However, to explore mechanisms, there is a need to use appropriate animal models and protocols to address these hypotheses.…”

(HIIT-The Track) High-Intensity Interval Training for People with Parkinson’s Disease: Individual Response Patterns of (Non-)Motor Symptoms and Blood-Based Biomarkers—A Crossover Single-Case Experimental Design

“…Timeline and assessment schedule for demographics, clinical characteristics, and all outcome measures (disease severity, disease status, cognitive function, activities of daily living, mood, quality of life, sleep quality, motor capacity, daily mood, cognitive function, and sleep quality, physical (in)activity, blood biomarkers of neuroplasticity, and neurodegeneration) are presented elsewhere [ 16 ]. In total, 6 outcome measures (motor symptoms, disease status, cognitive function, mood, blood biomarkers of neuroplasticity, and neurodegeneration) are presented here.…”

“…The heterogeneous disease course is an additional confounding factor to work toward optimal treatment strategies. Gaining insight into individual response patterns of, primarily, motor and non-motor symptoms as well as the stability and responsiveness of blood biomarkers of neuroplasticity and neurodegeneration to alternating exercise modalities (HIIT and CAE) using a crossover single-case experimental design (SCED) [ 16 ] was, therefore, the aim of this study. Elucidating these patterns is valuable in the preparation of a well-powered RCT to, ultimately, develop appropriate exercise interventions which adequately alleviate disease burden.…”