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Journal of Clinical Sleep Medicine :... Jul 2024Despite its widespread use in patients with isolated rapid eye movement sleep behavior disorder (iRBD), the cognitive effect of clonazepam is uncertain. This study aimed...
STUDY OBJECTIVES
Despite its widespread use in patients with isolated rapid eye movement sleep behavior disorder (iRBD), the cognitive effect of clonazepam is uncertain. This study aimed to investigate the effect of cumulative clonazepam on cognitive function in patients with iRBD.
METHODS
Demographic characteristics, baseline cognitive test, and most recent cognitive test information were collected retrospectively. Based on cumulative clonazepam doses, patients were classified into 4 subgroups: group 1, < 365 mg (1 mg × 1 year); group 2, 365 mg to < 1,095 mg (1 mg × 3 years); group 3, 1,095 mg to < 2,190 mg (1 mg × 6 years); and group 4, 2,190 mg or more. Cognitive test scores were calculated as scores adjusted for age, education, and sex.
RESULTS
This study included 101 patients with iRBD (63 males). Groups 1, 2, 3, and 4 had 14, 20, 32, and 35 patients, respectively. In within-group comparisons, follow-up Digit Span Backward test and the Trail Making Test A scores decreased in group 3, and follow-up Trail Making Test A and the Trail Making Test B scores decreased significantly in group 4. In the multiple regression analysis to determine influential factors on cognitive decline, cumulative clonazepam dose did not show a significant correlation with any cognitive domain. Follow-up cognitive function showed significant correlation only with baseline cognitive function.
CONCLUSIONS
Memory and executive functions tended to decline in patients with iRBD. However, there was no significant effect of cumulative clonazepam. There was no evidence that long-term use of clonazepam was related to cognitive decline in patients with iRBD.
CITATION
Lee M, Kim TK, Hong JK, Yoon I-Y. Minimal effect of long-term clonazepam on cognitive function in patients with isolated rapid eye movement sleep behavior disorder. . 2024;20(7):1173-1182.
Topics: Humans; Clonazepam; Male; Female; REM Sleep Behavior Disorder; Retrospective Studies; Cognition; Middle Aged; Aged; Neuropsychological Tests; Cognitive Dysfunction
PubMed: 38494993
DOI: 10.5664/jcsm.11126 -
Brain and Behavior Mar 2024Rapid eye movement behavior disorder (RBD) is a parasomnia characterized by the loss of skeletal muscle atonia during the rapid eye movement (REM) sleep phase. On the... (Review)
Review
Rapid eye movement sleep behavior disorder and its relation to Parkinson's disease: The potential of graph measures as brain biomarkers to identify the underlying physiopathology of the disorder.
Rapid eye movement behavior disorder (RBD) is a parasomnia characterized by the loss of skeletal muscle atonia during the rapid eye movement (REM) sleep phase. On the other hand, idiopathic RDB (iRBD) is considered the prelude of the various α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Consequently, over 40% of patients eventually develop PD. Recent neuroimaging studies utilizing structural magnetic resonance imaging (s-MRI), diffusion-weighted imaging (DWI), and functional magnetic resonance imaging (fMRI) with graph theoretical analysis have demonstrated that patients with iRBD and Parkinson's disease have extensive brain abnormalities. Thus, it is crucial to identify new biomarkers that aid in determining the underlying physiopathology of iRBD group. This review was conducted systematically on the included full-text articles of s-MRI, DWI, and fMRI studies using graph theoretical analysis on patients with iRBD, per the procedures recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search was conducted through the PubMed and Google scholar databases concentrating on studies from September to January 2022. Based on the three perspectives of integration, segregation, and centrality, the reviewed articles demonstrated that iRBD is associated with segregation disorders in frontal and limbic brain regions. Moreover, this study highlighted the need for additional longitudinal and multicenter studies to better understand the potential of graph metrics as brain biomarkers for identifying the underlying physiopathology of iRBD group.
Topics: Humans; REM Sleep Behavior Disorder; Parkinson Disease; Brain; Synucleinopathies; Biomarkers
PubMed: 38494747
DOI: 10.1002/brb3.3460 -
Journal of Clinical Neuroscience :... Apr 2024The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS). Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables.
METHODS
Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318).
RESULTS
Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0-100, i.e., low-high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0-100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0-100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of -0.78, -0.57 and -0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women.
CONCLUSION
Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.
Topics: Humans; Female; Quality of Life; Restless Legs Syndrome; Surveys and Questionnaires; Physical Examination
PubMed: 38489955
DOI: 10.1016/j.jocn.2024.02.027 -
Neurology Apr 2024Cognitive impairments are common in idiopathic REM sleep behavior disorder (iRBD), in which the cholinergic degeneration of nucleus basalis of Meynert (NBM) may play an...
BACKGROUND AND OBJECTIVES
Cognitive impairments are common in idiopathic REM sleep behavior disorder (iRBD), in which the cholinergic degeneration of nucleus basalis of Meynert (NBM) may play an important role. However, the progressive changes of NBM, the relationship between progressive NBM degeneration and progression of cognitive impairments, and whether degeneration of the NBM can predict cognitive decline in patients with iRBD remain unclear. This study aimed to investigate the cross-sectional and longitudinal microstructural alterations in the NBM of patients with iRBD using free-water imaging and whether free water in the NBM is related to cognitive, mood, and autonomic function.
METHODS
We compared the baseline free-water values in the NBM between 59 healthy controls (HCs), 57 patients with iRBD, 57 patients with Parkinson disease (PD) with normal cognition (PD-NC), and 64 patients with PD with cognitive impairment (PD-CI). Thirty patients with iRBD and 40 HCs had one longitudinal data. In patients with iRBD, we explored the associations between baseline and longitudinal changes of free-water values in the NBM and clinical characteristics and whether baseline free-water values in the NBM could predict cognitive decline.
RESULTS
IRBD, PD-NC, and PD-CI groups had significantly increased free-water values in the NBM compared with HCs, whereas PD-CI had higher free-water values compared with iRBD and PD-NC. In patients with iRBD, free-water values in the NBM were progressively elevated over follow-up and correlated with the progression of cognitive impairment and depression. Free-water values in the NBM could predict cognitive decline in the iRBD group. Furthermore, we found that patients with iRBD with cognitive impairment had higher relative change of free-water value in the NBM compared with patients with iRBD with normal cognition over follow-up.
DISCUSSION
This study proves that free-water values in the NBM are elevated cross-sectionally and longitudinally and are associated with the progression of cognitive impairment and depression in patients with iRBD. Moreover, the free-water value in the NBM can predict cognitive decline in patients with iRBD. Whether free-water imaging of the NBM has the potential to be a marker for monitoring progressive cognitive impairment and predicting the conversion to dementia in synucleinopathies needs further investigation.
Topics: Humans; Parkinson Disease; REM Sleep Behavior Disorder; Basal Nucleus of Meynert; Cross-Sectional Studies; Cognitive Dysfunction; Water
PubMed: 38489578
DOI: 10.1212/WNL.0000000000209220 -
Journal of Parkinson's Disease 2024The movement toward prevention trials in people at-risk for Parkinson's disease (PD) is rapidly becoming a reality. The authors of this article include a genetically... (Review)
Review
The movement toward prevention trials in people at-risk for Parkinson's disease (PD) is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019 S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with PD. These authors participated as speakers, panelists, and moderators in the "Planning for Prevention of Parkinson's: A Trial Design Forum" hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson's (PwP) and retired family physician, an expert in patient engagement in Parkinson's, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson's community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.
Topics: Humans; Parkinson Disease; REM Sleep Behavior Disorder; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Genetic Predisposition to Disease; Male; Biomedical Research
PubMed: 38489198
DOI: 10.3233/JPD-230436 -
Dental and Medical Problems 2024This commentary on sleep medicine explores whether the potential relationship between sleep bruxism (SB), masticatory muscle pain (MMP) and sleep breathing disorders...
This commentary on sleep medicine explores whether the potential relationship between sleep bruxism (SB), masticatory muscle pain (MMP) and sleep breathing disorders (SBDs)contributes to improving the management of co-occurring conditions.The paper is divided into 2 sections: (1) reviewing the debate on SB nosology; and (2) based on the publications from the Martynowicz & Wieckiewicz research group, exploringthe role of intermittent hypoxia as a putative mechanism endotype that may link such co-occurrence among individuals for whom characteristics are not yet clear.
Topics: Humans; Sleep Bruxism; Masticatory Muscles; Sleep; Pain; Hypoxia
PubMed: 38488764
DOI: 10.17219/dmp/175686 -
The American Journal of Medicine Jun 2024
Topics: Humans; Restless Legs Syndrome; COVID-19; SARS-CoV-2; Adult; Male; Female
PubMed: 38485109
DOI: 10.1016/j.amjmed.2024.03.004 -
Sleep Jun 2024This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep...
Electroencephalographic spectro-spatial covariance patterns related to phenoconversion in isolated rapid eye movement sleep behavior disorder and their longitudinal trajectories in α-synucleinopathies.
STUDY OBJECTIVES
This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies.
METHODS
We assessed 47 participants, including 35 patients with iRBD and 12 healthy controls (HC), through baseline eye-closed resting EEGs. Patients with iRBD underwent follow-up EEG assessments and 18 patients with iRBD converted (12 to Parkinson's disease (PD), 6 to dementia with Lewy bodies [DLB]) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined.
RESULTS
At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve [AUC] = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman's rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters.
CONCLUSIONS
Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.
Topics: Humans; Male; Female; REM Sleep Behavior Disorder; Aged; Electroencephalography; Parkinson Disease; Lewy Body Disease; Synucleinopathies; Middle Aged; Longitudinal Studies; Disease Progression
PubMed: 38482885
DOI: 10.1093/sleep/zsae052 -
Expert Opinion on Drug Metabolism &... Mar 2024Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In... (Review)
Review
INTRODUCTION
Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated.
AREAS COVERED
The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options.
EXPERT OPINION
α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.
Topics: Humans; Dopamine Agonists; Calcium Channels; Restless Legs Syndrome; Ligands; Gabapentin
PubMed: 38482850
DOI: 10.1080/17425255.2024.2329738 -
Nature and Science of Sleep 2024Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst...
BACKGROUND
Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD).
METHODS
A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups.
RESULTS
Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures.
CONCLUSION
The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.
PubMed: 38482468
DOI: 10.2147/NSS.S435201