This study will investigate the impact of three common exercise modalities, cardiovascular, resistance, and multimodal (i.e., a combination of the previous two) training, on sleep quality and architecture in persons with Parkinson's disease (PD). Furthermore, the project will investigate whether the potential positive exercise-induced changes in sleep are associated with improvements in different quality of life (QoL)-related aspects. Participants will perform either cardiovascular training (CT), resistance training (RT), multimodal training (MT), or will be allocated to a control condition (i.e., waiting list - CON) for 12 weeks. Training will be performed three times/week. The assessments will be conducted at baseline, post-intervention, and follow-up (i.e. 8 weeks after the intervention) by assessors blinded to the participants' group allocation.

Background: Over 100,000 Canadians are currently living with PD. Every year, 6,600 new cases are diagnosed and this number is expected to double by 2031. Almost all (98%) of those persons experience sleep problems, which can appear even before the onset of the cardinal motor symptoms of the disease, affecting multiple aspects of their QoL. Persons with PD also show alterations in sleep architecture, which are clinically relevant as they have been associated with a faster disease progression. Since medications used to reduce sleep problems in PD have potential adverse side effects, exercise has been proposed as a potential non-pharmacological alternative to improve sleep quality and architecture in people with PD. However, the most beneficial intervention to improve sleep in this clinical population is still to be determined.

Objective: 1) To conduct a 12-week RCT comparing the effects of CT, RT, MT, and CON on both objective and subjective measures of sleep quality and architecture in patients with mild-to-moderate PD; 2) To assess whether, regardless of the exercise modality, positive changes in sleep quality and architecture mediate exercise-induced improvements in aspects directly related to QoL such as cognitive and motor function.

Design: A four-arm, parallel-group, multi-site, single-blinded RCT with assessments performed at baseline (T0) and after 12 weeks of training (T1), as well as at 8 weeks post-intervention (T2), by assessors blinded to the participants' group allocation.

Methods: After completing T0, participants will be randomly allocated into four groups using a sequence created and held by a central randomization service (https://www.randomizer.at) using a 1:1:1:1 ratio. Permuted blocks of varying sizes to ensure balance over time will be used. Adherence to the training programs and training intensity progression will be monitored by trainers who will track attendance and record responses to exercise (e.g., HR) during training sessions. Participants who will miss training sessions due to valid reasons (e.g., doctor appointments) will be offered make-up sessions to complete the full 36 training sessions. Participants who do not complete 80% of the training (>27 training sessions) over the 12-week, develop injuries that preclude safety during training, or desire to stop the program, will be excluded.

Changes in objective and subjective measures of sleep quality will be assessed with polysomnography and the PD sleep scale version 2, respectively. Sleep architecture will be measured with polysomnography. Motor and cognitive function will be assessed with the Unified PD Rating Scale part III and the Scale for Outcomes in PD-Cognition, respectively. Fatigue, psychosocial functioning and QoL will be assessed with the PD Fatigue Scale, the Scale for Outcomes in PD-Psychosocial and the PD QoL Scale, respectively. The plasma concentration of different inflammatory biomarkers will be assessed using enzyme-linked immunosorbent assays (ELISA) kits following the instructions provided by the manufacturers. Cardiorespiratory fitness will be assessed with a graded exercise test (GXT) performed on a recumbent stepper.

Expected results: 1) MT will be more effective than RT, CT, and CON at improving objective and subjective sleep quality and sleep architecture; 2) Sleep architecture improvements, regardless of the type of exercise performed, will mediate enhancements in cognition and motor function; 3) Improvements in sleep quality (i.e., sleep efficiency), regardless of the type of exercise performed, will mediate enhancements in different QoL-related aspects such as fatigue and psychological functioning.

Impact: This will be the first study comparing the effect of MT, CT and RT on sleep quality and architecture and investigating whether these changes mediate improvements in cognitive and motor function as well as QoL-related aspects (e.g., fatigue). The results of the study will provide important information to design more personalized exercise-based treatments, which are patient-oriented and aimed at optimizing the effect of sleep on cognitive and motor function as well as QoL in PD.

Inclusion Criteria:

• Persons with mild-moderate idiopathic Parkinson's Disease (Modified Hoehn & Yahr Scale stages 0.5-3.5);
• On a stable dosage of medication during the previous month;
• Having poor sleep quality defined as a score > 15 in the PDSS-2 and/or reporting subjective sleep complaints affecting their sleep quality;

Exclusion Criteria:

• Having atypical parkinsonism, dementia, stroke, or any other neurological condition;
• Presenting severe untreated obstructive sleep apnea (OSA);
• Having a Montreal Cognitive Assessment (MoCA) score <18
• Having a Beck Depression Inventory score >31;
• Having absolute contraindications to exercise;
• Having severe osteoporosis;
• Participating in an exercise or drug trial during the period of the study;
• Exceeding the physical activity levels recommended for the general population (≥150 minutes/week of moderate-intensity or ≥75 minutes/week of vigorous-intensity cardiovascular activity) and/or strengthening activities ≥2 days/week.

Assessors will be blinded to the participants' group allocation