Arousal characteristics in patients with Parkinson’s disease and isolated rapid eye movement sleep behavior disorder

Abstract

Study objectives Patients diagnosed with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and Parkinson’s disease (PD) have altered sleep stability reflecting neurodegeneration in brainstem structures. We hypothesize that neurodegeneration alters the expression of cortical arousals in sleep. Methods We analyzed polysomnography data recorded from 88 healthy controls (HC), 22 iRBD patients, 82 de novo PD patients without RBD and 32 with RBD (PD+RBD). These patients were also investigated at a 2-year follow-up. Arousals were analyzed using a previously validated automatic system, which used a central EEG lead, electrooculography, and chin electromyography. Multiple linear regression models were fitted to compare group differences at baseline and change to follow-up for arousal index (ArI), shifts in electroencephalographic signals associated with arousals, and arousal chin muscle tone. The regression models were adjusted for known covariates affecting the nature of arousal. Results In comparison to HC, patients with iRBD and PD+RBD showed increased ArI during REM sleep and their arousals showed a significantly lower shift in α-band power at arousals and a higher muscle tone during arousals. In comparison to HC, the PD patients were characterized by a decreased ArI in NREM sleep at baseline. ArI during NREM sleep decreased further at the 2-year follow-up, although not significantly Conclusions Patients with PD and iRBD present with abnormal arousal characteristics as scored by an automated method. These abnormalities are likely to be caused by neurodegeneration of the reticular activation system due to alpha-synuclein aggregation.

Sleep stability in isolated rapid eye movement sleep behavior disorder, Parkinson's disease, and dementia with Lewy bodies

“…This suggests higher susceptibility of PD patients to cortical activation during the lighter stages of sleep. Although it is difficult to make comparisons, because of different methodologies, this finding seems in discordance with studies reporting an inferior number of arousals in NREM sleep in PD compared with controls 18,23 . On one hand, if we could consider, as Sommerauer et al, 23 that the response to arousing stimuli is pathologically low in PD, possibly due to a failure in autonomic control caused by neurodegeneration of pontine nuclei, our finding could suggest that PD patients are less altered, in this regard, than patients with iRBD and DLB.…”

“…Although it is difficult to make comparisons, because of different methodologies, this finding seems in discordance with studies reporting an inferior number of arousals in NREM sleep in PD compared with controls. 18,23 On one hand, if we could consider, as Sommerauer et al, 23 that the response to arousing stimuli is pathologically low in PD, possibly due to a failure in autonomic control caused by neurodegeneration of pontine nuclei, our finding could suggest that PD patients are less altered, in this regard, than patients with iRBD and DLB. On the other hand, a higher frequency of arousals could be connected to an increase of arousing stimuli in PD patients, suggesting that other factors, particular to this disorder, like motor dysfunction or the effects of dopaminergic drugs, could be contributing to more severe sleep fragmentation, as discussed below.…”

“…This goes against a previous study that has found a higher frequency of arousals during REM sleep in iRBD and PD patients with RBD. 18 On the contrary, differences in arousal indices were no longer significant after adjusting for medication differences. This could mean that dopaminergics, more frequently used in PD, could promote arousals in this disorder, while acetylcholinesterase inhibitors, more frequently used in DLB, could have a protective effect on arousal in this population.…”

“…Christensen et al 17 have found REM and NREM sleep stability to be diminished in PD and iRBD patients compared with controls. Abnormal arousal characteristics were found in PD and iRBD 18 . However, we have found no studies that can provide a direct comparison between these three disorders regarding non‐REM sleep features.…”

“…Abnormal arousal characteristics were found in PD and iRBD. 18 However, we have found no studies that can provide a direct comparison between these three disorders regarding non-REM sleep features. Because not all PD and DLB patients have RBD, it is also important to understand to which categorical division sleep structure changes should be ascribed: presence/absence of RBD versus disease type (iRBD, PD, DLB).…”