The Effect of OSA on Brain Waste Clearance

Launched by WOOLCOCK INSTITUTE OF MEDICAL RESEARCH · Oct 30, 2022

Keywords

ClinConnect Summary

Dementia is a neurodegenerative disease characterized by cognitive dysfunction affecting aspects of memory and learning. Although the mechanisms that underlie the pathophysiology of dementia are still unclear, in the past decade there has been a focus on the adverse impact of sleep disturbance on brain waste disposal via the glymphatic system. The glymphatic system is a recently discovered brain-wide perivascular passageway that transports toxic neuro-metabolites (e.g.: amyloid beta, or Aβ) out of the brain to the blood via the cerebrospinal fluid. Newer research has shown that the glymphat...

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Eligibility criteria

• Inclusion Criteria:
• • Community dwelling adults aged 35-65 years.
• • Polysomnography-confirmed severe OSA with apnea hypopnea index (AHI) ≥ 30/hour, with Non-Rapid Eye Movement (NREM) AHI ≥ 15/hour.
• • Established CPAP use for treatment of OSA with compliance of \> 3 months, with ≥ 5 hours use per night for \> 5 nights per week.
• • Willing to withdraw from CPAP use for 14 nights.
• • Able to give informed verbal and written consent.
• • Fluent in spoken, and comprehension of English.
• Exclusion Criteria:
• • Commercial drivers (e.g.: drivers of heavy vehicles, public passenger vehicles, or vehicles requiring dangerous goods driver license).
• • History of severe cardiovascular disease (e.g.: stroke, myocardial infarction, atrial fibrillation).
• • Presence of cognitive impairment and/or established diagnosis of dementia.
• • Regular use of medications which affect sleep (e.g.: benzodiazepines, opioids, stimulants, sedating antihistamines).
• • Regular 24-hour shift workers, presence of jetlag, or history of trans-meridian travel (crossing 2 or more time zones) in the past 2 weeks.
• • Advice against withdrawal of CPAP treatment, as determined by the participant's treating physician or study physician.
• • Vulnerable to driving impairment without CPAP therapy/upon withdrawal of CPAP therapy, as assessed by: (a) positive response(s) to screening questions in the modified ASTN-Motor Vehicle Accident Questionnaire, reporting driving accidents and/or impairments prior to established CPAP therapy; AND/OR (b) the participant's treating physician.
• • Prior history of severe COVID-19 infection involving significant neurological symptoms (e.g.: reduced level of consciousness, delirium, encephalopathy) - warranting hospitalization.
• • Current COVID-19 infection and/or experience of ongoing symptoms/sequelae following a recent COVID-19 infection.
• * Not up to date with the COVID-19 vaccination schedule - as per the current Australian Technical Advisory Group on Immunization (ATAGI) definition for individuals aged 16 years and over - at the time of writing this Protocol, defined as having:
• • 1. Received 2 primary doses of any Therapeutic Goods Administration (TGA)-approved or TGA-recognized COVID-19 vaccine at least 14 days apart (except for the Janssen COVID-19 vaccine, where only 1 primary dose is required); PLUS
• • 2. A booster dose of a TGA-approved COVID-19 vaccine (Pfizer, Moderna or AstraZeneca) at a recommended interval of 3-6 months after the receipt of 2nd primary dose; OR
• • 3. For severely immunocompromised individuals: received 3 primary doses of any TGA-approved or TGA-recognized COVID-19 vaccine, with dose 3 administered within 6 months of receiving dose 2.
• • Other medical conditions deemed by study physicians to warrant exclusion.