Trial Outcomes & Findings for Is Obstructive Sleep Apnea Important in the Development of Alzheimer's Disease? (NCT NCT05094271)

Last Updated: 2026-05-11

Results Overview

The number of times a person stops breathing and periods of shallow breathing with a marked decrease in blood oxygen concentration every hour on average. A score lower than five indicates normal sleep (no sleep apnea), 5-15 indicates mild sleep apnea, 15-30 indicates moderate sleep apnea, and a score greater than 30 indicates severe sleep apnea. Result specified as change from room air condition to oxygen condition during the crossover trial

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

182 participants

Primary outcome timeframe

Over 8 hours on each of the two crossover treatment nights

Results posted on

2026-05-11

Participant Flow

Participants were recruited from the University of California San Diego sleep clinic and via online advertisement across the San Diego area. Recruitment and enrollment occurred between October 8, 2021 and April 1, 2025.

182 participants were consented to take part in the study. 40 did not meet neurocogntive criteria. 40 did not have sleep apnea during their baseline sleep study, however, 10 of these participants were assigned to a control group for neuroanatomical scans. Of the remaining 112, 24 declined to take part in the randmoized trial following their baseline sleep study.

Participant milestones

Participant milestones
Measure	Non-OSA Controls Participants determined not to have obstructive sleep apnea based on their baseline sleep study. These individuals will not take part in randomized treatment trials but will be used as a healthy control group for neuroanatomical scan analyses.	Crossover Only (Oxygen > Air) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night.	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Overall Study STARTED	10	18	20	7	7	9	7	5	5
Overall Study COMPLETED	10	17	18	7	7	9	7	4	5
Overall Study NOT COMPLETED	0	1	2	0	0	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Non-OSA Controls Participants determined not to have obstructive sleep apnea based on their baseline sleep study. These individuals will not take part in randomized treatment trials but will be used as a healthy control group for neuroanatomical scan analyses.	Crossover Only (Oxygen > Air) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night.	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Overall Study Lost to Follow-up	0	1	2	0	0	0	0	1	0

Baseline Characteristics

Is Obstructive Sleep Apnea Important in the Development of Alzheimer's Disease?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-OSA Controls n=10 Participants Participants determined not to have obstructive sleep apnea based on their baseline sleep study. These individuals will not take part in randomized treatment trials but will be used as a healthy control group for neuroanatomical scan analyses.	Crossover Only (Oxygen > Air) n=17 Participants This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night.	Crossover Only (Air > Oxygen) n=18 Participants This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) n=9 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) n=4 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) n=5 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.	Total n=84 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 3.2 • n=44 Participants	69.5 years STANDARD_DEVIATION 4.1 • n=10 Participants	71.2 years STANDARD_DEVIATION 4.9 • n=30 Participants	69.0 years STANDARD_DEVIATION 1.3 • n=1054 Participants	69.0 years STANDARD_DEVIATION 4.0 • n=97 Participants	69.4 years STANDARD_DEVIATION 3.9 • n=488 Participants	68.9 years STANDARD_DEVIATION 3.8 • n=825 Participants	68.3 years STANDARD_DEVIATION 1.9 • n=40 Participants	68.0 years STANDARD_DEVIATION 1.7 • n=295 Participants	69.6 years STANDARD_DEVIATION 3.9 • n=27 Participants
Sex: Female, Male Female	5 Participants n=44 Participants	8 Participants n=10 Participants	8 Participants n=30 Participants	4 Participants n=1054 Participants	5 Participants n=97 Participants	3 Participants n=488 Participants	3 Participants n=825 Participants	1 Participants n=40 Participants	1 Participants n=295 Participants	38 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=44 Participants	9 Participants n=10 Participants	10 Participants n=30 Participants	3 Participants n=1054 Participants	2 Participants n=97 Participants	6 Participants n=488 Participants	4 Participants n=825 Participants	3 Participants n=40 Participants	4 Participants n=295 Participants	46 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=44 Participants	3 Participants n=10 Participants	0 Participants n=30 Participants	1 Participants n=1054 Participants	2 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=44 Participants	14 Participants n=10 Participants	18 Participants n=30 Participants	6 Participants n=1054 Participants	5 Participants n=97 Participants	8 Participants n=488 Participants	6 Participants n=825 Participants	4 Participants n=40 Participants	5 Participants n=295 Participants	76 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=44 Participants	0 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	0 Participants n=97 Participants	1 Participants n=488 Participants	1 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	2 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=44 Participants	0 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=44 Participants	1 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	1 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	1 Participants n=40 Participants	1 Participants n=295 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=44 Participants	1 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=44 Participants	0 Participants n=10 Participants	2 Participants n=30 Participants	0 Participants n=1054 Participants	1 Participants n=97 Participants	0 Participants n=488 Participants	1 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	10 Participants n=44 Participants	13 Participants n=10 Participants	16 Participants n=30 Participants	7 Participants n=1054 Participants	4 Participants n=97 Participants	8 Participants n=488 Participants	5 Participants n=825 Participants	3 Participants n=40 Participants	4 Participants n=295 Participants	70 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=44 Participants	1 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	1 Participants n=97 Participants	1 Participants n=488 Participants	1 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=44 Participants	1 Participants n=10 Participants	0 Participants n=30 Participants	0 Participants n=1054 Participants	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=40 Participants	0 Participants n=295 Participants	1 Participants n=27 Participants
Region of Enrollment United States	10 participants n=44 Participants	17 participants n=10 Participants	18 participants n=30 Participants	7 participants n=1054 Participants	7 participants n=97 Participants	9 participants n=488 Participants	7 participants n=825 Participants	4 participants n=40 Participants	5 participants n=295 Participants	74 participants n=27 Participants
Baseline apnea-hypopnea index	6.9 units on a scale STANDARD_DEVIATION 4.3 • n=44 Participants	40.6 units on a scale STANDARD_DEVIATION 14.4 • n=10 Participants	44.9 units on a scale STANDARD_DEVIATION 15.1 • n=30 Participants	40.1 units on a scale STANDARD_DEVIATION 36.4 • n=1054 Participants	39.2 units on a scale STANDARD_DEVIATION 19.5 • n=97 Participants	36.4 units on a scale STANDARD_DEVIATION 21.4 • n=488 Participants	56.5 units on a scale STANDARD_DEVIATION 26.6 • n=825 Participants	42.7 units on a scale STANDARD_DEVIATION 33.5 • n=40 Participants	40.9 units on a scale STANDARD_DEVIATION 23.4 • n=295 Participants	42.6 units on a scale STANDARD_DEVIATION 21.2 • n=27 Participants

PRIMARY outcome

Timeframe: Over 8 hours on each of the two crossover treatment nights

Population: Only participants involved in the crossover portion of the trial were assessed for this Outcome Measure

Outcome measures

Outcome measures
Measure	Oxygen n=65 Participants Oxygen treatment night data for participants who took part in the crossover trial	Room Air n=65 Participants Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Apnea Hypopnea Index - Crossover	34.9 units on a scale Standard Deviation 18.1	39.6 units on a scale Standard Deviation 18.7	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Over 8 hours on each of the two crossover treatment nights

Population: Only participants involved in the crossover portion of the trial were assessed for this Outcome Measure

A method used to measure respiratory stability of the negative feedback chemoreflex control system using a specialized Positive Airway Pressure machine called a pCrit. The overall loop gain of the ventilatory system reflects the ratio of the ventilatory response to the disturbance that elicited the response (LG = ventilatory response/ventilatory disturbance). The higher the loop gain, the potentially more unstable the respiratory control system becomes. Result specified as change from room air condition to oxygen condition during the crossover trial

Outcome measures

Outcome measures
Measure	Oxygen n=65 Participants Oxygen treatment night data for participants who took part in the crossover trial	Room Air n=65 Participants Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Loop Gain (LG) - Crossover	0.52 ratio Standard Deviation 0.15	0.60 ratio Standard Deviation 0.15	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Two 1-hour long scans

Population: Only a subsample of participants were scanned (n=20) for this portion of the trail which was independent of the treatment portion. Group 1 consists of enrolled individuals who were not randomized to treatment arms as they did not have OSA at baseline. Group 2 is a compound group consisting of participants with OSA at baseline and randomized to different treatment arms.

MRI and PET Scans. This study will examine pre-clinical Alzheimer's disease with OSA patients using brain imaging (structural MRI and amyloid/tau PET). MRI will be conducted to provide a structural image suitable for coregistering the PET image and observing white matter integrity. The scan should take 35 minutes. These will be MPRAGE images collected using the standard ADNI protocol at the in-house 3T MRI scanner at the University of California San Diego Altman Clinical and Translational Research Institute (ACTRI). The PET scan should take 70-90 minutes and uses the 18F-MK6240 tracer. Result given is the Standardized Uptake Value Ratio (SUVR) of tau protein in the BRAAK1-2 regions, the earliest regions to develop tau pathology in Alzheimer's disease

Outcome measures

Outcome measures
Measure	Oxygen n=10 Participants Oxygen treatment night data for participants who took part in the crossover trial	Room Air n=10 Participants Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Neuroimaging - BRAAK12 tauPET	0.91 Standardized Uptake Value Ratio Standard Deviation 0.22	0.92 Standardized Uptake Value Ratio Standard Deviation 0.16	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: Only participants involved in the parallel portion of the trial were assessed for this Outcome Measure

A self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life. Result specified as change from week 1 to week 12 during the parallel treatment trial

Outcome measures

Outcome measures
Measure	Oxygen Oxygen treatment night data for participants who took part in the crossover trial	Room Air Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) n=9 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) n=4 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) n=5 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Epworth Sleepiness Scale (ESS) - Parallel	—	—	—	-0.50 questionnaire sum score Standard Deviation 1.97	0.14 questionnaire sum score Standard Deviation 2.85	-0.22 questionnaire sum score Standard Deviation 1.72	-0.43 questionnaire sum score Standard Deviation 2.76	1.00 questionnaire sum score Standard Deviation 0.82	-1.8 questionnaire sum score Standard Deviation 1.92

SECONDARY outcome

Timeframe: 12 weeks

Population: Only participants involved in the parallel portion of the trial were assessed for this Outcome Measure

A 19-item, self-rated questionnaire designed to measure sleep quality and disturbance over the past month. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality. Result specified as change from week 1 to week 12 during the parallel treatment trial

Outcome measures

Outcome measures
Measure	Oxygen Oxygen treatment night data for participants who took part in the crossover trial	Room Air Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) n=9 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) n=4 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) n=5 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Pittsburgh Sleep Quality Index (PSQI) - Parallel	—	—	—	-1.29 questionnaire sum score Standard Deviation 2.36	-0.71 questionnaire sum score Standard Deviation 3.50	0.78 questionnaire sum score Standard Deviation 2.99	-1.57 questionnaire sum score Standard Deviation 3.42	-1.50 questionnaire sum score Standard Deviation 3.42	0.80 questionnaire sum score Standard Deviation 2.49

SECONDARY outcome

Timeframe: 12 weeks

Population: Only participants involved in the parallel portion of the trial were assessed for this Outcome Measure

A 7-item self-report form to assess insomnia severity. Total score categories: 0-7 = No clinically significant insomnia, 8-14 = Subthreshold insomnia, 15-21 = Clinical insomnia (moderate severity), 22-28 = Clinical insomnia (severe). Result specified as change from week 1 to week 12 during the parallel treatment trial

Outcome measures

Outcome measures
Measure	Oxygen Oxygen treatment night data for participants who took part in the crossover trial	Room Air Room air treatment night data for participants who took part in the crossover trial	Crossover Only (Air > Oxygen) This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) n=9 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) n=7 Participants This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) n=4 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Parallel Only (Oxygen) n=5 Participants This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.
Insomnia Severity Index (ISI) - Parallel	—	—	—	-1.43 questionnaire sum score Standard Deviation 0.98	-3.14 questionnaire sum score Standard Deviation 4.74	-0.89 questionnaire sum score Standard Deviation 2.42	-4.00 questionnaire sum score Standard Deviation 2.83	-0.50 questionnaire sum score Standard Deviation 3.11	0.60 questionnaire sum score Standard Deviation 2.30

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Parallel Only (Oxygen) n=5 participants at risk This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen.	Parallel Only (Positive Airway Pressure) n=5 participants at risk This arm included participants who took part in the parallel treatment trial portion of the study only. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Non-OSA Controls n=10 participants at risk Participants determined not to have obstructive sleep apnea based on their baseline sleep study. These individuals will not take part in randomized treatment trials but will be used as a healthy control group for neuroanatomical scan analyses.	Crossover Only (Oxygen > Air) n=18 participants at risk This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night.	Crossover Only (Air > Oxygen) n=20 participants at risk This arm included participants who took part in the crossover treatment trial portion of the study only. In the single-night crossover treatment trial, subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night.	Crossover (Oxygen > Air) and Parallel (Positive Airway Pressure) n=7 participants at risk This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received positive airway pressure therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Oxygen > Air) and Parallel (Oxygen) n=7 participants at risk This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects were instrumented with a nasal cannula to receive 2 liters/min supplemental oxygen on the first night and room air on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.	Crossover (Air > Oxygen) and Parallel (Positive Airway Pressure) n=9 participants at risk This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented to received PAP therapy automatically titrated between 4 cmH2O 20 cmH2O.	Crossover (Air > Oxygen) and Parallel (Oxygen) n=7 participants at risk This arm included participants who took part in both the crossover treatment trial and parallel treatment trial portions of the study. In the single-night crossover treatment trial, subjects subjects were instrumented with room air on the first night and a nasal cannula to receive 2 liters/min supplemental oxygen on the second night. In the 12-week parallel treatment trial, subjects were instrumented with a nasal cannula to receive 2L/min supplemental oxygen.
Injury, poisoning and procedural complications Pain	0.00% 0/5 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/5 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/10 • from enrollment until end of follow-up, median duration 5 weeks	5.6% 1/18 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/20 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/7 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/7 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/9 • from enrollment until end of follow-up, median duration 5 weeks	0.00% 0/7 • from enrollment until end of follow-up, median duration 5 weeks

Additional Information

Atul Malhotra

University of California, San Diego

Phone: 8582462154

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place