Adherence to continuous positive airway pressure for the treatment of obstructive sleep apnea in neurodegenerative diseases: A systematic review

Abstract

Obstructive sleep apnea (OSA) is prevalent in patients with neurodegenerative diseases and is associated with worse outcomes. Positive airway pressure therapy has the potential to benefit these patients but can be challenging in this population. Our primary aim was to describe positive pressure therapy adherence. Secondarily, we aimed at identifying identify predictors of adherence to treatment in adults with neurodegenerative diseases and OSA, and report the effect of PAP adherence on outcomes such as cognitive function, quality of life and patient/caregiver satisfaction. We performed a systematic review of the literature and identified seventeen studies, eight reporting on adults with obstructive sleep apnea and mild cognitive impairment (MCI) and/or Alzheimer's disease (AD), 6 with Parkinson's disease (PD), and 3 with multiple system atrophy (MSA). Meta-analyses were not performed due to lack of systematic and standardized reporting of the primary outcome. Study duration ranged from 6 weeks to an average of 3.3 years. PAP adherence definition was widely variable between studies. Attrition rates ranged from 12% to 75%. In MCI/AD, adherence rates ranged from 28% to 61% (study duration range: 3 weeks to 3.3 years). Younger age, race (white) and better CPAP confidence scores at 1 week were associated with more CPAP use while APOE4 positive and unmarried individuals were more likely to abandon CPAP. In most studies, adherent patients had improvement in excessive daytime sleepiness, depressive symptoms, sleep quality, ability to manage daily activities and certain aspects of cognition (composite score or global cognition, psychomotor speed, executive function), as well as less cognitive decline over time. Caregiver satisfaction was also better in PAP adherent patients in one study. In PD, 15-25% of individuals refused treatment with PAP upfront, and attrition ranged from 8 to 75%. Adherent patients used their device for an average of 3h27 to 5h12 per night (study duration range: 6 weeks to 12 months). Longer disease duration, worse motor symptoms or sleep quality and lower % of REM sleep were identified as predictors of lower PAP adherence in a preliminary study, while race (non-white) and sex (women) were linked to lower adherence in a large retrospective study. In the study reporting the highest attrition rate (75%), individuals had lower educational levels. PAP adherence improved daytime sleepiness, anxiety symptoms, sleep architecture and quality and global non-motor symptoms. However, in one short-term (3 weeks) study, there was no improvement in neuropsychological testing composite score. Three studies on MSA patients suffering from sleep-disordered breathing showed that most patients are accepting of PAP (69-72%) with an average nightly use of 4h42 to 6h18. Floppy epiglottis was more frequently seen in patients discontinuing PAP in one study. In one study, four adults with MSA and long-term PAP use reported better sleep and improved vigilance. Survival time was no different between treated and untreated individuals. In conclusion, PAP therapy is challenging in patients with OSA and NDD, as evidenced by the considerable attrition and low adherence rates reported in this systematic review. There is emerging evidence proposing OSA a treatable target to prevent clinical and functional deterioration in patients with neurodegenerative diseases and addressing potential barriers to PAP adherence is paramount to maximize adherence. Our systematic review outlines several of these potential barriers, underscoring the need for future studies to standardize the definition of and explore long-term adherence to PAP therapy and assess interventions that can optimize adherence in this patient population.

Keywords: Cognitive impairment; Neurodegenerative disease; Obstructive sleep apnea; Positive airway pressure therapy; Sleep disordered breathing.