for people ages 65-85 (full criteria)
at La Jolla, California
study started
completion around
Principal Investigator
by Atul Malhotra
Headshot of Atul Malhotra
Atul Malhotra



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.


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.


OSA, Sleep Apnea, Obstructive Sleep Apnea, Alzheimer Disease, sleep, Sleep Disorder, Alzheimer, Apnea, Sleep Apnea Syndromes, Supplemental Oxygen, Continuous Positive Airway Pressure Machine, Room Air, Supplemental Oxygen during PSG, Room Air during PSG, Supplemental Oxygen for 3 Months, PAP Therapy for 3 Months


You can join if…

Open to people ages 65-85

  1. Age 65-85 years
  2. Gender: Men or Women
  3. MOCA > 26
  4. Independently living and able to drive
  5. OSA (AHI ≥ 15/h) or no OSA
  6. 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 CAN'T join if...

  1. Currently smoking
  2. History of COPD or asthma
  3. Heart Failure Class III or IV, unstable cardiovascular disease, or uncontrolled hypertension
  4. Neuromuscular Disease
  5. Drowsy Driving (ESS > 18/24)
  6. Inability to complete study procedures, such as questionnaire that are only available/validated in English
  7. Lack of decisional capacity to provide informed consent
  8. 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
  9. Presence of a brain tumor or lobar stroke
  10. Current drug or alcohol abuse/dependence
  11. Prisoners


  • UCSD Sleep Research accepting new patients
    La Jolla California 92037 United States

Lead Scientist at UCSD

  • Atul Malhotra
    Professor, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 733 research publications


accepting new patients
Start Date
Completion Date
University of California, San Diego
Phase 1 research study
Study Type
Expecting 260 study participants
Last Updated