Sleep, Sleep Apnea, Sleep Apnea Syndromes
Conditions
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTBrain MRI, cognitive testing, bloodwork
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.
Sponsors
University of Edinburgh
Dr. Andrew Lim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in perivascular space volume | Baseline and 4 months | 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. |
| Change from baseline in DTI fractional anisotropy on voxel-wise basis | Baseline and 4 months | 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. |
| Change from baseline in a summary measure of arterial pulsatility | Baseline and 4 months | 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). |
| Change from baseline in perivascular lactate measured by MR spectroscopy | Baseline and 4 months | 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). |
| Change from baseline in cerebrovascular reactivity on a voxel-wise basis | Baseline and 4 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 24-hour blood pressure | Baseline and 4 months | We will quantify the main effect of CPAP treatment on 24-hour blood pressure (as measured by the ambulatory blood pressure monitor). |
| Change from baseline in cognitive performance | Baseline and 4 months | 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). |
| Change from baseline in sleep duration and fragmentation | Baseline and 4 months | We will quantify the main effect of CPAP treatment on sleep duration and fragmentation (as measured by the GENEActiv). |
| Change from baseline in severity of sleep apnea, % deep NREM sleep, and hypoxemia | Baseline and 4 months | We will quantify the main effect of CPAP treatment on severity of sleep apnea, % deep NREM sleep, and hypoxemia (as measured by the WatchPAT). |
| Change from baseline in serum markers of metabolic, inflammatory, cardiovascular, and endothelial function | Baseline and 4 months | We will quantify the main effect of CPAP treatment on serum markers of metabolic, inflammatory, cardiovascular, and endothelial function (as measured by blood tests). |
| Change from baseline in urinary measures of sympathetic nervous system | Baseline and 4 months | We will quantify the main effect of CPAP treatment on urinary measures of sympathetic nervous system (as measured with urine test). |
Countries
Canada
Contacts
Primary ContactAndrew Centen, MSc
Outcome results
None listed