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

NCT05094271 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 200228
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (OSA) is common in older adults and has recently been implicated in pathogenesis of Alzheimer's disease (AD). Research has shown that sleep disruptions have caused memory impairment. Sleep apnea is a form of sleep disruption. We would like to examine how obstructive sleep apnea may contribute to the progression of Alzheimer's disease.

Conditions

OSA; Sleep Apnea; Obstructive Sleep Apnea; Alzheimer Disease

Keywords

sleep; OSA; Sleep Apnea; Obstructive Sleep Apnea; Alzheimer Disease; Sleep Disorder; Alzheimer

Outcome Measures

Primary Outcomes (3)

• Apnea Hypopnea Index - Crossover

  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

  Over 8 hours on each of the two crossover treatment nights

• Loop Gain (LG) - Crossover

  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

  Over 8 hours on each of the two crossover treatment nights

• Neuroimaging - BRAAK12 tauPET

  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

  Two 1-hour long scans

Secondary Outcomes (3)

• Epworth Sleepiness Scale (ESS) - Parallel

  12 weeks

• Pittsburgh Sleep Quality Index (PSQI) - Parallel

  12 weeks

• Insomnia Severity Index (ISI) - Parallel

  12 weeks

Study Arms (4)

Supplemental Oxygen during PSG

ACTIVE COMPARATOR

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Other: Supplemental Oxygen

Room Air during PSG

PLACEBO COMPARATOR

Subjects will be instrumented with a nasal cannula to receive 2L/min of pressurized room air. The room air will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Other: Room Air

Supplemental Oxygen for 3 Months

EXPERIMENTAL

Over a 12-week period, participants randomized to receive supplemental Oxygen for treatment of OSA will be contacted weekly to be asked about their adherence. Participants' adherence will also be monitored remotely through cloud-based monitoring.

Other: Supplemental Oxygen

PAP Therapy for 3 Months

EXPERIMENTAL

Over a 12-week period, participants randomized to receive supplemental PAP therapy for treatment of OSA will be contacted weekly to be asked about their adherence. Participants' adherence will also be monitored remotely through cloud-based monitoring.

Device: Continuous Positive Airway Pressure Machine

Interventions

Room Air OTHER

Subjects will be instrumented with a nasal cannula to receive 2L/min pressurized room air. The room air will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Also known as: Placebo

Room Air during PSG

Supplemental Oxygen OTHER

Subjects will be instrumented with a nasal cannula to receive 2L/min supplemental oxygen. The oxygen will be kept at a fixed rate, however, the participant will be titrated to receive a max of 4 liters per min to maintain sats \>90% based on oximetry readings.

Also known as: Oxygen, O2

Supplemental Oxygen during PSG; Supplemental Oxygen for 3 Months

Continuous Positive Airway Pressure Machine DEVICE

Continuous positive airway pressure is a form of positive airway pressure ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person.

Also known as: CPAP, PAP

PAP Therapy for 3 Months

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-85 years
• Gender: Men or Women
• MOCA \> 26
• Independently living and able to drive
• OSA (AHI ≥ 15/h) or no OSA
• Subjects must consent to waiving their right to obtain their PHS score (since the score is not yet actionable and could lead to social stress and ethical dilemmas)

You may not qualify if:

• Currently smoking
• History of COPD or asthma
• Heart Failure Class III or IV, unstable cardiovascular disease, or uncontrolled hypertension
• Neuromuscular Disease
• Drowsy Driving (ESS \> 18/24)
• Inability to complete study procedures, such as questionnaire that are only available/validated in English
• Lack of decisional capacity to provide informed consent
• Participants in whom magnetic resonance imaging Magnetic Resonance Imaging \[MRI\] is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant
• Presence of a brain tumor or lobar stroke
• Current drug or alcohol abuse/dependence
• Prisoners

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Sleep Research

La Jolla, California, 92037, United States

Location

Related Publications (2)

• Harding CD, Holloway BM, DeYoung PN, Kwan C, Djonlagic I, Ancoli-Israel S, Banks SJ, Malhotra A. Subjective daytime sleepiness, not sleep quality or hypoxia, predicts sleep-dependent memory consolidation in a cohort of older adults. J Clin Sleep Med. 2025 Jul 1;21(7):1217-1226. doi: 10.5664/jcsm.11648.

  PMID: 40135690 RESULT

• Holloway BM, Harding CD, DeYoung P, Kwan CG, Avetisyan L, Lui KK, Ancoli-Israel S, Banks SJ, Djonlagic I, Malhotra A. Comorbid insomnia and sleep apnea is associated with worse verbal episodic memory in older females. J Clin Sleep Med. 2025 Dec 1;21(12):2129-2138. doi: 10.5664/jcsm.11902.

  PMID: 41025403 DERIVED

MeSH Terms

Conditions

Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Alzheimer Disease; Sleep Wake Disorders

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Nervous System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Results Point of Contact

• Title: Atul Malhotra
• Organization: University of California, San Diego

sleepresearch@health.ucsd.edu

8582462154

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: If subjects have been randomized to receive room air, subjects will have a nasal cannula with pressurized room air to avoid unblinding.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: October 26, 2021
• Study Start: October 8, 2021
• Primary Completion: June 12, 2025
• Study Completion: June 12, 2025
• Last Updated: May 11, 2026
• Results First Posted: May 11, 2026

Record last verified: 2026-03

Locations

US (1)