The Latest Articles on Sleep Behavior Disorder and Neurodegeneration
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Sleep Behavior Disorder and Neurodegeneration.
Title: Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder
Authors: Jiri Nepozitek, Zsoka Varga, Simona Dostalova, Pavla Perinova, Jiri Keller, Simon Robinson, Veronika Ibarburu, Iva Prihodova, Ondrej Bezdicek, Evzen Ruzicka, Karel Sonka & Petr Dusek
Type: Research Article
Abstract:
REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.
Access this article: https://doi.org/10.1038/s41531-023-00557-2
Title: Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study
Authors: Stephen Joza, Michele T. Hu, Ki-Young Jung, Dieter Kunz, Dario Arnaldi, Jee-Young Lee, Luigi Ferini-Strambi, Elena Antelmi, Friederike Sixel-Döring, Valérie Cochen De Cock, Jacques Y. Montplaisir, Jessica Welch, Han-Joon Kim, Frederik Bes, Pietro Mattioli, Kyung Ah Woo, Sara Marelli, Giuseppe Plazzi, Brit Mollenhauer, Amelie Pelletier, Jamil Razzaque, Jun-Sang Sunwoo, Nicola Girtler, Claudia Trenkwalder, Jean-François Gagnon, Ronald B. Postuma, for the International REM Sleep Behavior Disorder Study Group
Type: Research article
Abstract:
Introduction
Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia.
Methods
IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing.
Results
Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes.
Discussion
In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion.
Access this article: https://doi.org/10.1002/alz.13386
Title: Constipation is linked to accelerated cognitive and motor decline in isolated REM sleep behavior disorder
Authors: Kyung Ah Woo, Seoyeon Kim, Hyunwoo Nam, Yu Kyeong Kim, Beomseok Jeon, Jee-Young Lee
Type: Short Communication
Abstract:
Introduction
Constipation is associated with higher clinical severity and predicts cognitive decline in Parkinson's disease (PD). Whether the non-motor marker is associated with unfavorable motor and cognitive trajectories from the prodromal stage remains unclear.
Methods
In a longitudinal prospective cohort of subjects with isolated REM sleep behavior disorders (iRBD), subjects underwent repeated MDS-UPDRS and Mini-Mental Status Examination (MMSE) assessments. Generalized-estimating-equations (GEE) regression model was used to compare the time-dependent trajectories of MDS-UPDRS-III and MMSE scores between subjects with and without constipation at baseline.
Results
Twenty-nine subjects with constipation at baseline (iRBD+constipation) and 24 without (iRBD-constipation) were followed over 4.085 ± 2.645 years. The iRBD+constipation group presented faster decline of both MDS-UPDRS-III and MMSE scores, with additional estimated annual progression of +1.242 and −0.713 points, respectively, compared to the iRBD-constipation group (time*group p < 0.05).
Conclusion
Constipation in isolated RBD is associated with accelerated progression of cognitive impairment and motor symptoms.
Access this article: https://doi.org/10.1016/j.parkreldis.2023.105775
Title: Pharmacological interventions targeting α-synuclein aggregation triggered REM sleep behavior disorder and early development of Parkinson's disease
Authors: Lida Du, Xiaoli He, Xiaonuo Fan, Xiaoya Wei, Linhao Xu, Tuo Liang, Chunbo Wang, Ya Ke, Wing-ho Yung
Type: Review
Abstract:
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the diagnosis of Parkinson's disease (PD). As RBD could serve as a biomarker for early PD developments, pharmacological interventions targeting α-synuclein aggregation triggered RBD could be applied toward early PD progression. However, robust therapeutic guidelines toward PD-induced RBD are lacking, owing in part to a historical paucity of effective treatments and trials. We reviewed the bidirectional links between α-synuclein neurodegeneration, progressive sleep disorders, and RBD. We highlighted the correlation between RBD development, α-synuclein aggregation, and neuronal apoptosis in key brainstem regions involved in REM sleep atonia maintenance. The current pharmacological intervention strategies targeting RBD and their effects on progressive PD are discussed, as well as current treatments for progressive neurodegeneration and their effects on RBD are discussed. We also evaluated emerging and potential pharmacological solutions to sleep disorders and developing synucleinopathies. This review provides insights into the mechanisms and therapeutic targets underlying RBD and PD, and explores bidirectional treatment effects for both diseases, underscoring the need for further research in this area.
Access this article: https://doi.org/10.1016/j.pharmthera.2023.108498
Title: Rapid eye movement sleep loss associated cytomorphometric changes and neurodegeneration
Authors: Amit Ranjan, Sudipta Biswas, Birendra Nath Mallick
Type: Review
Abstract:
Rapid eye movement sleep (REMS) is essential for leading normal healthy living at least in higher-order mammals, including humans. In this review, we briefly survey the available literature for evidence linking cytomorphometric changes in the brain due to loss of REMS. As a mechanism of action, we add evidence that REMS loss elevates noradrenaline (NA) levels in the brain, which affects neuronal cytomorphology. These changes may be a compensatory mechanism as the changes return to normal after the subjects recover from the loss of REMS or if during REMS deprivation, the subjects are treated with NA-adrenoceptor antagonist prazosin (PRZ). We had proposed earlier that one of the fundamental functions of REMS is to maintain the level of NA in the brain. We elaborate on this idea to propose that if REMS loss continues without recovery, the sustained level of NA breaks down neurophysiologically active compensatory mechanism/s starting with changes in the neuronal cytomorphology, followed by their degeneration, leading to acute and chronic pathological conditions. Identification of neuronal cytomorphological changes could prove to be of significance for predicting future neuronal (brain) damage as well as an indicator for REMS health. Although current brain imaging techniques may not enable us to visualize changes in neuronal cytomorphology, given the rapid technological progress including use of artificial intelligence, we are optimistic that it may be a reality soon. Finally, we propose that maintenance of optimum REMS must be considered a criterion for leading a healthy life.
Access this article: https://doi.org/10.1016/j.sleep.2023.07.022
