The Effects of Successful OSA Treatment on Memory and AD Biomarkers in Older Adults Study

Inclusion criteria

• Cognitively normal (TiCS ≥29)
• Age 55-85 years
• Moderate - severe OSA defined as AHI4 ≥20 events/hour or AHI3A\>40/hr using a hypopnea criterion of a 4% oxygen desaturation (AHI4) or 3% oxygen desaturation and/or EEG arousal (AHI3A), or equivalent based on in-home testing - Testing must have been completed in past 12 months or confirmed by repeat test
• Not currently on therapy for OSA and has not received treatment for OSA for at least 6months
• Able and willing to be treated for OSA (Treatment group)
• Fluency in English or Spanish

Exclusion criteria

• Documented diagnosis of chronic insomnia, or sleep onset insomnia based on Insomnia Severity Index - an answer of severe or very severe in the screening form
• Documented diagnosis of circadian rhythm disorder
• Any current use of supplemental oxygen
• Other sleep-related breathing disorders (central sleep apnea, etc) based on AASM criteria
• Current shift work involving night shift (regular work between 12am and 6am or night shift) within the past 6 mo
• Anticipated scheduled bariatric surgery within the next 3 months
• Chronic regular (\> 2 nights per week) of cannabis for sleep
• Chronic regular use (\> 2 nights per week) of sedatives/hypnotics for sleep
• Diagnosis of uncontrolled psychiatric disease in the last six months , and/or history of schizophrenia or bipolar disorder. Controlled conditions will include major depressive disorder, panic disorder, generalized anxiety disorder, OCD, substance use disorders, and alcohol abuse/dependence. Personality disorders and neurodevelopmental disorders (e.g. autism, ADHD) are allowed if cognition is within normal limits.
• Taking methylphenidate for ADHD. Unless on stable dose which will be reviewed by the PI to determine.
• Taking GLP-1 agonist semaglutide (Ozempic, Wegovy, Rybelsus), or tirzepatide (Mounjaro, Zepbound), or similar for weightloss, and planning to lose an additional 20lbs or more at the time of enrollment. PI Discretion for determination of why they are taking the drug based on conversation with subject and medical chart, will be documented in form of Note-to-file in the subject's records
• Presence of other comorbid condition that would lead to inability to complete the study protocol (including follow-up for 2 years), or that would affect cognition (e.g. clinically relevant endocrine or hematological conditions).
• Does not have a regular sleeping environment (i.e., sleeps in a different setting \> 2 nights per week).
• Currently pregnant or planning to become pregnant.
• Prior diagnosis of a Central nervous system (CNS) disease, such as multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, a loss of consciousness \> 24 hours, or traumatic brain injury as identified by the Cumulative Illness Rating Scale for Geriatrics (CIRS). Participants who are diagnosed with MCI or Alzheimer's disease based on neuropsychological testing will be excluded. Delirium in the last 12 months.
• Near-miss or prior automobile accident "due to sleepiness" within the past 12 months.
• Employed as a commercial driver during the study (for example, bus drivers, train engineers, airplane pilots).
• Any use of neuroleptics, benzodiazepines, barbiturates, opiates or anti-amyloid therapies.
• Use of other cognitive enhancing drugs will also be excluded if initiated in the last 3 months, or not on stable dose.
• Consumption of \>14 alcohol drinks per week, unless alcohol consumption can be reduced if initiated in the last 3 months.