The Brain Changes in Sleep Apnea Study

Study Overview
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Brief Summary
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Sleep is critical to human health, but insufficient and disrupted sleep caused by sleep apnea are common and have a major impact on brain health. However, there is still much that is not known about how sleep apnea damages the brain and what can be done to fix this. The Brain Changes in Sleep Apnea Study will look at the brain health of people with severe sleep apnea both before and after 4 months of treatment with a CPAP machine. Pre- and post-CPAP treatment, 80 participants with severe sleep apnea will undergo cognitive testing, blood and urine tests, a pulse wave velocity test, and an MRI. Also pre- and post-CPAP treatment, participants will wear a blood pressure monitor for 24 hours, wear an accelerometer watch for 8 nights to track the duration and quality of their sleep, and wear a device for 1 night of sleep to assess their breathing and blood oxygen levels. It is expected that there will be improvements in participants' brain health after 4 months of CPAP treatment.

Detailed Description
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Between January 2018 and February 2022, the Brain Changes in Sleep Apnea Study will recruit 80 adults with newly diagnosed severe sleep apnea attending the sleep clinics at Sunnybrook Health Sciences Centre (n=40) or the University of Edinburgh (n=40). Participants will undergo home-based assessment with 3 wearable devices (24 hours of ambulatory blood pressure monitoring, 8 nights of actigraphy to assess sleep duration and fragmentation, and 1 night of finger-probe peripheral arterial tonometry and oximetry to assess cardiorespiratory physiology including sleep apnea), completion of a sleep and health questionnaire, 24-hour collection of urine for assessing sympathetic nervous system activity, blood banking for endothelial biomarkers, cognitive evaluation, pulse wave velocity test, and an MRI of the brain, at 2 time points: 1) after initial polysomnographic diagnosis of sleep apnea but before the initiation of CPAP, and 2) after 4 months of CPAP treatment.

Official Title
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The Brain Changes in Sleep Apnea Study

Conditions
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Sleep, Sleep Apnea, Sleep Apnea Syndromes

Intervention / Treatment
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* Diagnostic Test: Brain MRI, cognitive testing, bloodwork


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed sleep apnea not on CPAP or any other treatment for sleep apnea; Apnea hypopnea index >=15 on diagnostic polysomnogram; Oxygen desaturation index >=10 or O2 saturation in sleep <90% for >15 minutes on diagnostic polysomnogram; Subjectively sleepy; Planning on starting CPAP for sleep apnea. Exclusion Criteria: Known history of stroke, transient ischemic attack, or other CNS disease; Unable to safely undergo MRI; Use of alpha-blocking agents; Persistent non-sinus arrhythmia; Severe pulmonary or cardiac diseases including COPD and CHF; Waking spO2<90%; History of panic disorder.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sleep apnea patients<br>80 patients recently diagnosed with severe sleep apnea will participate in the Brain Changes in Sleep Apnea Study. | Diagnostic Test: Brain MRI, cognitive testing, bloodwork<br>* Participants will undergo 3-Tesla MRI. Scan time will be about 1 hour and 15 minutes per subject per session at the Sunnybrook site. The protocol is designed to image SVD burden by quantifying PVS and WMH volumes, and image various physiological estimates on the brain. Participants will undergo the following cognitive tests: Behavioural Neurology Assessment-R (BNA-R), Montreal Cognitive Assessment (MOCA), Center for Epidemiologic Studies Depression Scale (CES-D), and BrainScreen. Blood samples will be assayed for inflammatory and endothelial function. Classical vascular risk factors will also be assessed. Once data collection is complete, DNA will be extracted from the frozen PBMC fraction and will be genotyped for APOE genotype and a panel of other single nucleotide polymorphisms known to be associated with cognition and cerebrovascular disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in perivascular space volume | We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on perivascular space volume. | Baseline and 4 months | 
| Change from baseline in DTI fractional anisotropy on voxel-wise basis | We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on DTI fractional anisotropy on voxel-wise basis. | Baseline and 4 months | 
| Change from baseline in a summary measure of arterial pulsatility | We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on arterial pulsatility (as measured by the pulse wave velocity test). | Baseline and 4 months | 
| Change from baseline in perivascular lactate measured by MR spectroscopy | We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on perivascular lactate (as measured by MR spectroscopy). | Baseline and 4 months | 
| Change from baseline in cerebrovascular reactivity on a voxel-wise basis | We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on cerebrovascular reactivity on a voxel-wise basis. | Baseline and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 24-hour blood pressure | We will quantify the main effect of CPAP treatment on 24-hour blood pressure (as measured by the ambulatory blood pressure monitor). | Baseline and 4 months | 
| Change from baseline in sleep duration and fragmentation | We will quantify the main effect of CPAP treatment on sleep duration and fragmentation (as measured by the GENEActiv). | Baseline and 4 months | 
| Change from baseline in severity of sleep apnea, % deep NREM sleep, and hypoxemia | We will quantify the main effect of CPAP treatment on severity of sleep apnea, % deep NREM sleep, and hypoxemia (as measured by the WatchPAT). | Baseline and 4 months | 
| Change from baseline in serum markers of metabolic, inflammatory, cardiovascular, and endothelial function | We will quantify the main effect of CPAP treatment on serum markers of metabolic, inflammatory, cardiovascular, and endothelial function (as measured by blood tests). | Baseline and 4 months | 
| Change from baseline in urinary measures of sympathetic nervous system | We will quantify the main effect of CPAP treatment on urinary measures of sympathetic nervous system (as measured with urine test). | Baseline and 4 months | 
| Change from baseline in cognitive performance | We will quantify the main effect of CPAP treatment on cognitive performance (as measured by our computerized battery, which includes the MoCA, BNA-R, and BrainScreen). | Baseline and 4 months |