NCT05094271

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 260 (estimated)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 65 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Aim 1: We will assess the endotypes (mechanisms) underlying OSA in elderly individuals known to be high risk for AD (vs. non-OSA matched controls) using novel recently validated simplified techniques which do not require burdensome complex overnight experiments to assess endotypes (primary outcome loop gain). We will further assess the predicted response to O2 therapy in terms of respiratory outcomes among elderly OSA patients with varying levels of loop gain and pharyngeal collapsibility. Hypothesis 1: A substantial proportion of high AD risk patients with OSA should be O2 responsive as predicted using pathophysiological assessments. Aim 2: We will perform an overnight mechanistic study of oxygen therapy vs. room air in high AD risk patients with OSA (recruited from Aim 1 and others if necessary). Given the frequent intolerance of PAP in elderly patients, we anticipate that oxygen therapy may be a viable therapeutic approach in this fragile population. We will focus on respiratory outcomes (primary outcome: apnea hypopnea index) but also assess sleep dependent memory consolidation on word pairs task given the major impact in the elderly. Hypothesis 2: O2, compared to room air, will improve OSA and neurocognitive outcomes in select elderly OSA patients at risk of AD. Aim 3: Preclinical AD with OSA and non-OSA controls, from Aim 1 will have structural and molecular brain imaging focusing on hippocampal atrophy as a predictor of memory consolidation. We will also assess amyloid and tau in the medial temporal region as function of OSA severity and as a predictor of neurocognitive function. This aim will lay the groundwork for designing a robust clinical trial using neuroimaging outcomes. Hypothesis 3: Impairment in memory consolidation is a function of hippocampal size in OSA patients at risk of AD. Aim 4: We will perform a pilot randomized trial of oxygen vs. PAP therapy in OSA patients with preclinical AD. Hypothesis 4: In preclinical AD with OSA, oxygen will be a viable therapeutic strategy to improve memory.

Conditions

• OSA
• Sleep Apnea
• Obstructive Sleep Apnea
• Alzheimer Disease

Interventions

Type	Name	Description
OTHER	Supplemental Oxygen	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.
DEVICE	Continuous Positive Airway Pressure Machine	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.
OTHER	Room Air	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.

Timeline

• Start date: 2021-06-30
• Primary completion: 2025-05-20
• Completion: 2025-05-20
• First posted: 2021-10-26
• Last updated: 2024-12-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study