CPAP to Treat Cognitive Dysfunction in MS

Inclusion Criteria

• Age of 18-70 years at screening
• Diagnosis of clinically definite MS
• Willingness to undergo in-lab baseline polysomnography (PSG) and positive airway pressure (PAP) titration (if needed)
• Willingness to undergo 2 separate 90-minute cognitive testing sessions
• Either one of the following:

Score of >=2 sleep apnea risk factors on the "STOP-Bang" sleep apnea screening questionnaire. The STOP-Bang questionnaire is a screening tool consisting of eight items which reflect OSA risk factors. STOP-Bang scores of ≥3 indicate elevated risk for moderate-severe OSA in the general population, and scores as low as 2 are frequently seen in MS patients with OSA, based on previous data from the PI).

OR

Have a pre-existing diagnosis of OSA based on a previous overnight sleep study (either home study or in-lab) but have not yet started using PAP therapy on a compliant basis. *If OSA was NOT diagnosed by a U-M in-lab sleep study within the past year prior to screening, subjects must be willing to get new baseline in-lab U-M PSG as part of study.

• Willingness to start treatment with PAP if OSA present

Exclusion Criteria

• Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, PAP use, or reliable longitudinal follow-up
• Cardiopulmonary conditions that may increase sleep apnea risk
• Current treatment, such as PAP, for obstructive or central sleep apnea
• History of surgical treatment for OSA
• Nervous system diseases other than MS that may predispose subjects to OSA (such as Parkinson's disease, amyotrophic lateral sclerosis, or recent stroke)
• History of concomitant central nervous system disease that could influence cognition, such as large vessel territory stroke, Alzheimer's disease, Parkinson's disease, or Lewy body dementia
• Concomitant systemic autoimmune disease with secondary central nervous system involvement (including CNS lupus or neurosarcoidosis).
• Pregnancy
• Evidence of clinical MS relapse within the last 30 days prior to enrollment
• Systemic high dose steroid use (1 gram IV methylprednisolone daily for 3-5 days or equivalent)for an MS relapse within the last 30 days prior to enrollment
• Unwillingness to initiate PAP therapy if clinically indicated
• Severe depression at screening per the Patient Health Questionnaire-8 (PHQ-8) (The PHQ-8 is a brief, self-administered questionnaire that evaluates core symptoms associated with major depressive disorder. Scores range from 0 to 24 based on the frequency and severity of depressive symptoms over the previous two weeks.)
• Anticipated initiation, dosage change, or discontinuation in medications that could, per the opinion of the investigators, influence cognitive test scores from baseline to follow-up, including MS disease modifying therapies, hypnotic agents, narcotic-based medications, benzodiazepines, antispasmodics, or 4-aminopyridine
• ESS scores >= 16 on baseline visit
• Subjects with extreme OSA accompanied by signs of cardiopulmonary compromise (RDI>60 respiratory events per hour with severe nocturnal hypoxia or unstable ECG rhythms on PSG), will be excluded unless they are randomized to immediate PAP arm
• Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility