Continuous Positive Airway Pressure, Arousability and Links to Mechanisms in Obstructive Sleep Apnea

Mean daily average of CPAP use over 3 months

Executive function is assessed using the validated NIH Toolbox Cognition Battery's Flanker inhibitory control and attention test. In a Flanker task, participants are required to indicate the left-right orientation of a centrally presented stimulus while inhibiting attention to the potentially incongruent stimuli that surround it (i.e., the flankers, typically two on either side). Primary outcome is the overall percent of correct responses in incongruent trials.

Sleep questionnaire of subjective sleepiness. Total score range of 0-24; scores above 10 suggest excessive sleepiness.

Measures how sleepiness affects daily life, with scores ranging from 5-20. Higher scores indicate better functioning and less impairment.

ISI is a validated 7-question survey. The total score range is 0-28 with higher scores indicating more severe insomnia.

T-score mean of 50 and a standard deviation (SD) of 10. Higher scores indicating more sleep disturbance.

T-score mean of 50 and a standard deviation (SD) of 10. Higher scores indicating more sleep disturbance.

Administered on standardized paper form by research associate. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper and participant connect numbers (Part A) and numbers with letters (Part B) in ascending order. Mean time to connect the "trail" in minutes.

Administered by participants via an iPad to assess processing speed. Participants are asked to quickly determine whether two stimuli are the same or not the same. Mean time in seconds.

Administered by participants via a computer to complete psychomotor vigilance task at the same time in the morning. Mean time in minutes to complete assessment of daytime vigilance = 1/reaction-time.

Administered by participants via an iPad to assess cognitive flexibility and attention. The participant is asked to match a series of picture pairs to a target picture.

Administered by participants via an iPad with audio instructions and feedback to assess recall. The participant is asked to recall A-B verbal paired associates word-pairs. Immediate recall occurs before sleep and delayed recall occurs after sleep.

Defined as: therapeutic efficacy × adjusted CPAP adherence. The therapeutic efficacy for OSA is "[AHI-baseline - AveAHI-3-months on CPAP] / AHI-baseline" and the adjusted CPAP adherence is objective AveCPAP use / AveSleep time (both in hours) over 3 months

Hypoxic burden (HB) is a sleep apnea metric that quantifies the total oxygen deprivation by measuring the depth and duration of blood oxygen drops (desaturations) during sleep, expressed as %-minutes per hour.

Sleep depth will be measured by an Odds Ratio Product (ORP), a continuous metric based on quantitative analysis of the EEG power spectra. High values indicate deeper sleep, with a range of 0 - 2.5.

Arousal intensity is measured on a scale between 0 and 9 (most intense) using a validated automated wavelet transformation method (Azarbarizin et al., Sleep 2014)

The average ventilatory burden per event is defined as the multiplication of the average ventilation during the respiratory event (i.e., event depth) and average duration of respiratory events. The total ventilatory burden (percentage eupnea × min/h) for each participant is defined as the multiplication of respiratory event rate (events/h) and average ventilatory area per event (percentage eupnea × min/event).

Mean concentration NfL (pg/ml) in the blood to assess neuronal injury and damage.

Mean concentration Aβ40 (pg/ml) in the blood (usually measured as a ratio with Aβ42 (Aβ42/40 ratio) to assess brain amyloid plaque buildup.

Mean concentration F2-isprostane (pg/ml) in the blood to assess oxidative stress.

Mean concentration oxidized LDL (pg/ml) in the blood to assess oxidative stress.

Mean concentration cortisol (pg/ml) in the blood to assess autonomic activation.

Mean concentration norepinephrine (pg/ml) in the blood to assess autonomic activation.

Mean systolic and diastolic blood pressure during a single 24-hour period at baseline and 3-month

Blood pressure variability during a single 24-hour period at baseline and 3-month

Mean nighttime BP dipping during a single 24-hour period at baseline and 3-month

Measured nightly from cloud-based remote monitoring adherence system

Measured nightly from cloud-based remote monitoring adherence system

FMD is a standard non-invasive technique for assessing endothelial function. FMD will be obtained using a standard method by a trained RA at the same time of the day after the baseline PSG and the 3-month follow-up. Two-dimensional longitudinal images will be acquired using Doppler ultrasound to assess arterial diameter and flow velocity (resting and hyperemic). Resting blood flow is estimated by time-averaging the pulsed Doppler signal obtained from a mid-vessel sample volume. The blood pressure cuff is then inflated to >50 mmHg above systolic pressure to occlude arterial inflow for 5 minutes. A cuff is then deflated, and a pulse wave and longitudinal images are obtained at 10 seconds and 60 seconds (hyperemia). The FMD is the percent increase in vessel diameter from baseline to hyperemia.