Rapid eye movement sleep without atonia constitutes increased risk for neurodegenerative disorders

Abstract

Objectives REM (rapid eye movement) sleep without atonia (RSWA) is a polysomnographic finding used in diagnosis of REM sleep behavior disorder (RBD). Clinical significance of idiopathic RSWA (iRSWA) unaccompanied by RBD is not known. We designed a prospective study to investigate whether iRSWA constitutes an increased risk for developing neurodegenerative disorders. Materials and methods Between January 2010 and December 2014, a total of 4362 patients underwent a full‐night video‐polysomnography. Upon detailed clinical and polysomnographical examination, patients with iRSWA and idiopathic RBD (iRBD) were enrolled into this study and followed up at every six months for at least 4 years up to 9 years. Results We had a total of 31 patients with iRBD and 67 patients with iRSWA. Mean age was higher in iRBD group than those in iRSWA group (P = .016). Restless legs syndrome/Willis‐Ekbom disease was significantly more common in patients with iRBD than those in patient with iRSWA (P < .001). Eighteen patients with iRSWA (26.8%) developed iRBD after 2.6 + 2.2 years. Six patients with iRSWA (8.9%) developed neurodegenerative disorders following 2.4 + 1.5 years; four were diagnosed as Parkinson's disease (PD) and two developed probable Alzheimer‐type dementia. In patients with iRBD, eight patients (25.8%) developed neurodegenerative disorders—all was Parkinson's disease—following 2.6 + 2.2 years. Development of neurodegenerative diseases was positively correlated with age (P < .001) and periodic leg movements in sleep in both groups (P < .010). Conclusions These results show that iRSWA may also be accepted as a risk factor in the development of PD or neurodegenerative diseases. Advanced age and periodic leg movements in sleep seem to be correlated with higher risk.

Predictors of RBD progression and conversion to synucleinopathies

“…By contrast, Dede and colleagues, studying 67 iRSWA patients for at least 4 years, reported that 26.8% developed RBD and 8.9% developed a neurodegenerative disorder. This study, however, lacked a control group to ascertain whether the progression was due to aging or by a genuine increased risk of iRSWA [ 38 ].…”

“…Risk influenced by the severity of the mutation [ 27 , 28 , 29 ••, 30 ] TMEM175 gene mutations The p.Q65P variant associated with increased rate of phenoconversion to a synucleinopathy [ 31 ••] SNCA gene CpG hypomethylation Associated with increased risk of progression of iRBD symptoms and phenoconversion [ 32 •] Neurophysiological RSWA Percentage of RSWA at baseline is a predictor of future phenoconversion. Tonic RSWA associated with higher risk of future conversion to parkinsonism, phasic RSWA associated with risk of future phenoconversion to dementia [ 33 , 34 •, 35 ] Isolated RSWA Conflicting results on its predicting role of future phenoconversion [ 36 , 37 , 38 ] EEG abnormalities Higher δ and θ power in the cortex and higher slow-to-fast power ratio in converters. Diffuse slowing of electrical activity associated with DLB; EEG slowing in temporal and occipital lobes associated with PD [ 39 , 40 ] Cyclic Alternating Pattern (CAP) CAP rate reduction in future converters to a neurodegenerative disease [ 41 ] Fluid p-tau/total tau ratio in CSF Reduced ratio in iRBD associated with phenoconversion at five years [ 31 ••] Imaging Presynaptic striatal dopamine terminals [ 123 I]FP-CIT SPECT and [ 99m TC]TRODAT-1 SPECT Progressive loss of presynapric dopamine terminals in the striatum associated with high risk of short-term conversion [ 42 , …”

Isolated dream‐enactment behaviours as a prodromal hallmark of rapid eye movement sleep behaviour disorder

“…Over recent decades, several studies have explored the ‘prodrome’ of RBD by using different definitions and terms (e.g., ‘prodromal’, ‘subclinical’, and ‘isolated’). The data supported that the emergence of isolated RBD features, such as documentation of RBE or RSWA during v‐PSG studies, would signify the presence of prodromal RBD (Dede et al, 2019; Eisensehr et al, 2003; Hogl et al, 2018; Kang et al, 2013; Sasai‐Sakuma et al, 2014; Sixel‐Doring et al, 2016; Stefani et al, 2015; Swetlik et al, 2020). Stefani et al (2015) followed 14 subjects with isolated RSWA (without DEB) for 8.6 years and found that 7.3% subjects converted to RBD and 71.4% presented with at least one neurodegenerative biomarker, respectively.…”

Morbidity, Mortality, and Conversion to Neurodegenerative Diseases in Patients with REM Sleep Behavior Disorder and REM Sleep without Atonia

“…Some patients may therefore not have fulfilled the criteria of dream enactment. However, we believe it is still relevant to include this group of patients in our study, especially since recent population studies have proposed that not only iRBD but also RSWA patients are in risk of converting to a neurodegenerative disorder [58, 59]. However, the cause of RSWA is not fully understood; some studies have found RSWA to be a prodromal marker of neurodegeneration, perhaps by preceding iRBD, whereas other studies have found RSWA as an incidental finding in the healthy population [59-63].…”