The Impact of Exercise on Irisin-BDNF Regulation in Obstructive Sleep Apnea

The Impact of Exercise on Irisin-Brain-Derived Neurotrophic Factor Regulation in Obstructive Sleep Apnea-Related Neuroinflammation: From Animal Model to Clinical Study

The goal of this clinical trial is to learn whether aerobic exercise can improve sleep and nervous system regulation in adults with mild to moderate obstructive sleep apnea (OSA). The study will also examine whether exercise changes blood markers related to inflammation and brain health.

The main questions this study aims to answer are:

1. Does four weeks of aerobic exercise change blood levels of irisin, brain derived neurotrophic factor (BDNF), and markers related to inflammation?
2. Does aerobic exercise improve sleep apnea, heart rate variability, cognitive function, daytime sleepiness, sleep quality, and daily functioning?

Researchers will compare an aerobic exercise group with a sleep education group to determine whether adding regular aerobic exercise provides additional benefits for people with mild to moderate OSA.

Participants will be randomly assigned to one of two groups.

Participants in the aerobic exercise group will:

1. Receive sleep education.
2. Complete four weeks of supervised treadmill exercise, three to five times per week. Each session will last about 45 to 60 minutes. Exercise intensity will be adjusted to each participant's heart rate and physical condition.

Participants in the comparison group will:

1. Receive sleep education about OSA, common symptoms, treatment options, and healthy sleep habits.
2. Practice the recommended healthy sleep habits at home during the four-week study period.

Participants in both groups will complete assessments before and after the four-week study period. These assessments will include an overnight sleep study, blood tests, heart rate measurements, cognitive tests, and questionnaires about daytime sleepiness, sleep quality, and daily functioning.

Detailed Description Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder characterized by repeated episodes of upper airway obstruction during sleep. These episodes can result in intermittent hypoxia, sleep fragmentation, oxidative stress, systemic inflammation, and autonomic nervous system imbalance. These physiological changes may also affect neuroplasticity, daytime functioning, and cognitive performance.

Intermittent hypoxia associated with OSA may contribute to increased inflammatory activity and altered regulation of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal survival and neuroplasticity. Irisin, an exercise-related myokine, has been proposed to have anti-inflammatory and neuroprotective effects and may be involved in the regulation of BDNF. However, the effects of structured aerobic exercise on the relationship among irisin, BDNF, inflammatory responses, autonomic nervous system regulation, sleep, and cognitive function in individuals with OSA remain unclear.

The purpose of this randomized controlled study is to investigate the effects of a four-week aerobic exercise intervention in adults with mild to moderate OSA. The study will examine whether aerobic exercise is associated with changes in circulating irisin, BDNF, inflammatory and anti-inflammatory markers, autonomic nervous system regulation, sleep-related outcomes, and cognitive function.

A total of 50 participants will be randomly assigned to either an aerobic exercise group or a sleep education control group, with 25 participants in each group. Participants in both groups will complete assessments before the intervention and again after four weeks.

Participants assigned to the aerobic exercise group will receive sleep education and participate in a supervised treadmill-based aerobic exercise program for four weeks. Exercise will be performed three to five times per week, with each session lasting approximately 45 to 60 minutes. Each exercise session will include a warm-up period, treadmill aerobic exercise, and a cool-down period. Exercise intensity will be individualized using heart rate reserve and will progressively increase over the four-week intervention period. Exercise sessions will be supervised by a physical therapist, and heart rate, blood pressure, oxygen saturation, and perceived exertion will be monitored to support exercise safety and individualized progression.

Participants assigned to the control group will receive sleep education covering basic information about OSA, common symptoms, related sleep problems, commonly used treatments, and principles of healthy sleep. Participants will be encouraged to practice the recommended sleep hygiene strategies during the four-week study period. A physical therapist will contact participants during the intervention period to follow up on their participation and general condition.

Assessments will be conducted before the intervention and after completion of the four-week intervention. These assessments will include polysomnography, blood sampling, heart rate variability analysis, cognitive testing, and sleep-related questionnaires.

Blood samples will be collected to examine exercise-related changes in irisin and inflammatory and anti-inflammatory biomarkers. The study will also investigate the BDNF-related response to exercise as part of the proposed irisin-BDNF regulatory pathway. Heart rate variability will be assessed to evaluate autonomic nervous system regulation and sympathetic-parasympathetic balance.

Cognitive assessments will evaluate domains including processing speed, attention, working memory, cognitive flexibility, and executive function. Sleep-related questionnaires will be used to assess daytime sleepiness and subjective sleep quality.

Through the integration of physiological biomarkers, sleep measurements, autonomic nervous system assessment, and cognitive outcomes, this study aims to better understand the potential mechanisms through which aerobic exercise may benefit individuals with mild to moderate OSA. The findings may provide evidence for the potential role of exercise as a non-pharmacological adjunctive strategy for improving OSA-related physiological and neurocognitive dysfunction.

Inclusion Criteria:

• Adults aged 20 years or older
• Diagnosed with mild to moderate pure obstructive sleep apnea by polysomnography (PSG)
• Body mass index (BMI) between 18 and 40 kg/m²

Exclusion Criteria:

• Central or mixed sleep apnea
• History of central or peripheral neurological disorders, such as dementia
• Musculoskeletal disorders that prevent participation in the prescribed exercise program
• Cardiovascular conditions associated with a high risk for exercise
• Severe psychiatric disorders
• Major head and neck diseases or cancer
• Structural abnormalities of the upper airway
• Pregnancy
• Alcohol abuse or circadian rhythm disruption, such as shift work
• Regular exercise within the 6 months before study enrollment, defined as approximately 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous-intensity exercise