Is REM sleep behavior disorder a friend or foe of obstructive sleep apnea? Clinical and etiological implications for neurodegeneration

Abstract

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during rapid eye movement sleep, associated with complex motor enactment of dreams. Obstructive sleep apnea (OSA) is a relatively common sleep disorder characterized by repetitive episodes of upper airway obstruction while sleeping, which can result in hypoxemia and sleep fragmentation. Even though the nature of RBD and OSA is different, OSA may sometimes be accompanied by RBD symptoms. Accordingly, it is reasonable to distinguish these 2 sleep disorders in people with dream enactment behaviors. Although RBD and OSA share similar sleep phenomena, their association has yet to be elucidated. Herein we draw attention to various RBD-mimicking conditions, RBD combined with OSA, and the relationship between RBD and OSA. Furthermore, the clinical implications of OSA in neurodegeneration and the optimized management of RBD combined with OSA are also discussed in this review.

Keywords: REM sleep behavior disorder; dream enactment behavior; neurodegeneration; obstructive sleep apnea.

Figure 1. Hypothetical mechanistic relationship between REM sleep behavior disorder, obstructive sleep apnea, and neurodegeneration.

A direct pathway from the sublaterodorsal nucleus and an indirect pathway from the magnocellular reticular formation to the spinal interneurons might contribute to muscle atonia during REM sleep. Lesions in the caudal brainstem involving these pathways are thought to eliminate atonia during REM sleep, leading to RBD. In RBD, a neurodegenerative process already occurs and OSA may hypothetically play an additive role in accelerating neurodegeneration via several mechanisms induced by repetitive hypoxia and sleep fragmentation. OSA is likely to have a deleterious impact on multiple brain areas, especially on the locus coeruleus, and promote the accumulation of abnormal proteins, such as α-synuclein, amyloid-β, or tau. NF-κB = nuclear factor-kappa B, OSA = obstructive sleep apnea, RBD = rapid eye movement sleep behavior disorder, REM = rapid eye movement, ROS = reactive oxygen species, TNF-α = tumor necrosis factor-alpha.