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

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. 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. 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). 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 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. 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.