The cholinergic system may play a role in the pathophysiology of residual excessive sleepiness in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12-14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.