Search Results (80)

REM sleep behavioral disorder (RBD) is of increasing interest in Parkinson’s disease (PD). Previous studies exploring the association between REM sleep without atonia (RWA) and clinical PD features or other objective sleep metrics are scarce and have used PSG findings. A mobile electroencephalography (EEG)/electrooculography (EOG) recording system with two channels can objectively measure sleep parameters, including RWA, during natural sleep at home. We investigated whether RWA measured on a portable recording device at home could be associated with clinical PD features or other sleep metrics using baseline data from the ZEAL study. Differences between patients with and without RWA was analyzed using ANCOVA test. REM sleep length was significantly longer in patients with RWA than in those without RWA. A multivariate comparison using ANCOVA showed a significant difference in log-transformed REM sleep duration of patients with RWA after adjustment for potential confounders (adjusted mean difference of 1.203; 95% confidence interval 0.468 to 1.937; p = 0.003). The strength of this study was that it evaluated the association between RWA during natural sleep at home and clinical variables as well as other sleep metrics. The major result was that patients with and without RWA did not differ in their clinical variables, and there was no relation between RWA and objective sleep metrics other than REM sleep. The duration of REM sleep may be associated with RWA during natural sleep at home. Full article

REM sleep behavior disorder (RBD) represents a prodromal manifestation of Parkinson’s disease (PD), reflecting the breakdown of inhibitory networks extending from the brainstem to the cortex. This review synthesizes pathological, physiological, and behavioral evidence to illustrate how early α-synuclein pathology disrupts REM-sleep atonia and motor automaticity through degeneration of pontomedullary and cholinergic–inhibitory circuits. The resulting failure of inhibitory precision links nocturnal REM sleep without atonia to daytime gait and postural abnormalities, framing RBD as a dynamic systems disorder rather than a purely sleep-related phenomenon. By examining this continuum across neurophysiological, behavioral, and clinical domains, the review highlights current knowledge gaps, particularly regarding the temporal dynamics of degeneration and compensation. It further integrates multimodal biomarkers that capture these transitions in vivo and discusses therapeutic strategies aimed at preserving inhibitory network integrity and delaying phenoconversion to overt Parkinsonian syndromes. Full article

L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles (EVs) are being explored as a potential source of biomarkers for Parkinson’s disease (PD) in peripheral blood. However, their utility remains controversial. In this study, we sought to investigate the proteome composition of L1CAM⁺-EVs isolated from human blood plasma and evaluate their potential as biomarkers for PD. L1CAM⁺-EVs were extracted from blood plasma using direct immunoprecipitation by employing magnetic beads coupled to an anti-L1CAM antibody. The Proximity Extension Assay platform, Olink Explore 3072, was used to analyze samples from 60 individuals: 20 healthy controls (HC), 20 patients with isolated REM sleep behavior disorder (iRBD), and 20 PD patients. Targeted proteomic analysis identified 2841 proteins in L1CAM⁺-EVs, of which 203 exhibited differential expression across groups. Although these changes were not statistically significant, after correction for multiple testing, a combination of 12 proteins could discriminate between PD and HC. Moreover, several proteins displayed trends toward upregulation or downregulation in PD and iRBD when compared with HC. These preliminary findings suggest that L1CAM⁺-EVs proteins show some potential as biomarkers for PD; however, further investigation and validation studies are required. Full article

Objective: To explore the value of multimodal molecular imaging in diagnosing and differentiating dementia with Lewy bodies (DLB). Methods: A retrospective analysis was conducted on clinical data and multimodal molecular imaging of 40 probable DLB patients treated at Peking Union Medical College Hospital (August 2017–December 2024). All 40 had ¹⁸F-FDG PET/CT; 15 had ¹³¹I-MIBG imaging; 11 had ¹⁸F-FP-CIT PET/CT. A total of 12 patients with poor cognition or atypical ¹⁸F-FDG PET/CT underwent ¹⁸F-AV45 PET/CT (2 also had ¹⁸F-PM-PBB3 imaging). A sex- and age-matched control group (cognitively normal, same-period health checkup ¹⁸F-FDG PET/CT) was included. ¹⁸F-FDG PET/CT images were visually and semi-quantitatively analyzed (ROI, SPM). ¹⁸F-AV45 PET/CT was assessed both visually and semi-quantitatively; ¹³¹I-MIBG imaging and ¹⁸F-FP-CIT PET/CT were visually evaluated. Results: The 40 DLB patients (29 males, 11 females; mean age 72 years) had distinct initial symptoms: 8 (20%) presented with cognitive decline as the first symptom, 23 (57.5%) with parkinsonian symptoms as the first symptom, and 9 (22.5%) with both symptoms occurring simultaneously. Mean intervals: 16.25 months from initial cognitive decline to parkinsonian symptoms, and 24.43 months from initial parkinsonian symptoms to cognitive decline. All had parkinsonian symptoms and cognitive impairment; 38 (95%) had visual hallucinations; and 26 (65%) had REM sleep behavior disorder. ¹⁸F-FDG PET/CT: 30(75%) showed typical occipital hypometabolism and posterior cingulate island sign; 10 (25%) had atypical findings. ¹³¹I-MIBG (15/15, 100%): cardiac sympathetic denervation. ¹⁸F-FP-CIT (10/11, 90.9%): basal ganglia dopaminergic damage. ¹⁸F-AV45 (9/12, 81.8%): positive. Semi-quantitative ¹⁸F-FDG analysis revealed parietal, occipital, and lateral temporal hypometabolism in DLB (left more severe than right). Conclusions: Dementia with Lewy bodies (DLB) presents with pre-onset parkinsonism and cognitive impairment, plus high rates of visual hallucinations and sleep disorders. Key imaging features—occipital hypometabolism/island sign on ¹⁸F-FDG PET/CT, cardiac sympathetic denervation on ¹³¹I-MIBG, and basal ganglia dopaminergic damage on ¹⁸F-FP-CIT—aid DLB diagnosis. ¹⁸F-AV45 PET/CT detects Aβ pathology in severely cognitively impaired patients, suggesting these DLB patients may have underlying AD pathology beyond DLB. Full article

Platelets are increasingly recognized as multifunctional cells with roles extending beyond hemostasis to immune regulation, inflammation, and neurodegeneration. Here, we performed RNA-Seq profiling of platelets from patients with idiopathic REM sleep behavior disorder (IRBD), dementia with Lewy bodies (DLB), Parkinson disease (PD), Alzheimer disease (AD), and healthy controls (CTRLs) to explore disease-specific transcriptomic signatures. Across all groups, the RNA class distribution was similar, dominated by mRNAs (78–80%) and long non-coding RNAs (lncRNAs; 15–16%). DLB platelets displayed a reduced proportion of lncRNAs, suggesting an impaired RNA regulation, whereas IRBD concentrated the highest number of disease-specific lncRNAs, half of which were Y-linked, consistent with the male predominance observed in alpha-synucleinopathies. Differential expression analysis (DEA) revealed extensive transcriptomic remodeling in IRBD and DLB, particularly affecting RNA processing, cytoskeletal organization, and platelet activation pathways, while PD and AD showed minimal changes. These findings suggest a progressive impairment of platelet activation and signaling across the DLB continuum, potentially mirroring neuronal dysfunction. The limited transcriptional deregulation in PD may reflect its pronounced biological heterogeneity, consistent with recent multidimensional disease models. Overall, our study highlights platelets as accessible indicators of early and disease-stage-specific molecular alterations in α-synucleinopathies. Full article

Parkinson’s disease (PD) is a multisystem disorder, with early changes extending beyond basal ganglia circuitries and involving non-dopaminergic pathways, including cerebellar networks. Whether cerebellar dysfunction reflects a compensatory mechanism or an intrinsic hallmark of disease progression remains unresolved. In this cross-sectional study, we examined how cerebellar γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx) systems, as well as their excitatory/inhibitory (E/I) balance, are modulated along the disease course. As to ascertain how these mechanisms contribute to motor and non-motor features in the premotor and early stages of PD, 18 individuals with isolated REM sleep behavior disorder (iRBD), 20 de novo, drug-naïve PD (dnPD), and 18 matched healthy controls underwent clinical, cognitive, and neuropsychiatric assessments alongside cerebellar magnetic resonance spectroscopy (MRS, MEGA-PRESS, 3T). While cerebellar neurotransmitter levels did not differ significantly across groups, dnPD patients exhibited a shift toward hyperexcitability in the E/I ratio, without correlation to clinical or cognitive measures. In contrast, in iRBD, an inverse relationship between heightened GABAergic activity and neuropsychiatric symptoms emerged. These findings suggest an early, dynamic cerebellar involvement, potentially reflecting compensatory modulation of altered basal ganglia output. Our results support cerebellar GABA MRS as a promising biomarker and open perspectives for targeting non-dopaminergic pathways in PD. Full article

Background: This study aims to investigate the association between the presence and severity of non-motor symptoms (constipation, REM sleep behavior disorder [RBD], hyposmia, and depression) and the severity of motor impairment in Parkinson’s disease (PD). Methods: We used data from Parkinson’s Progression Markers Initiative (PPMI), comprising patients with established PD, prodromal PD, and healthy controls. Motor disability was evaluated with the MDS-UPDRS part III. Non-motor symptoms were assessed with standardized scales for constipation (MDS-UPDRS part I sub-item), depression (15-item GDS), RBD questionnaire (RBDQ), and hyposmia (UPSIT). The relationships between non-motor symptoms and motor severity were explored using linear regression models (adjusted for age/sex). Results: Constipation was significantly more prevalent in PD and prodromal PD and independently associated with greater motor severity in both groups (p < 0.001). Constipation also correlated with increased freezing and falls. Depressive symptoms were similar across groups, but in prodromal PD, higher GDS scores were associated with worse UPDRS III scores (p = 0.02), as well as higher freezing and fall scores. Hyposmia was strongly reduced in PD and prodromal PD compared with controls but was not independently associated with motor severity. Higher RBDQ scores were associated with worse motor impairment in PD, but not in prodromal PD after adjustment. Conclusions: Constipation and REM sleep behavioral disorder were independent correlates of worse motor severity in prodromal and established PD, whereas depressive symptoms predicted more severe parkinsonism only within the prodromal phase. Full article

Background: Sleep bruxism (SB) is increasingly recognized not merely as a movement disorder but as a multifactorial condition in which physiological, behavioral, and contextual factors converge. Objective: To comprehensively characterize SB in young adults, integrating polysomnography (PSG) and surface electromyography (sEMG) to describe sleep architecture, periodic limb movements (PLMs), and masticatory muscle activity; compare these parameters with matched controls; and explore clinical correlations relevant to dental practice and individualized management. Methods: Forty university adults (20 PSG-confirmed SB; 20 controls) underwent PSG assessment of total sleep time, sleep stages, arousals, apnea, oximetry, and PLMs. EMG activity of the masseter and temporalis muscles was recorded in 37 participants (18 SB, 19 controls). Statistical analyses included t-tests, Mann–Whitney U tests, and multivariate logistic regression to identify independent predictors of SB. Results: SB participants exhibited higher bruxism event counts (p ≤ 0.001; PS = 0.94), increased PLMs (p ≤ 0.01; PS = 0.75), shorter REM sleep duration (p = 0.04; d = 0.69), and higher bruxism-related arousal indices (p ≤ 0.001; PS = 83.4). Left masseter activity differed significantly (p = 0.03; d = 0.50), while other muscle measures showed no significant differences. Logistic regression identified age (OR = 0.59, p = 0.02), PLMs (OR = 0.96, p = 0.03), and REM sleep duration (OR = 0.98, p = 0.05) as independent predictors, explaining 58% of the variance. Conclusions: These findings provide a comprehensive profile of SB in young adults. Integrating PSG, sEMG, and oral assessments supports early diagnosis, personalized management, and interdisciplinary collaboration to prevent complications. Full article

Background/Objectives: We present a novel approach for detecting generalized sleep pathologies through the fractal analysis of single-channel electroencephalographic (EEG) signals. We propose that the fractal scaling exponent of permutation entropy time series serves as a robust biomarker of pathological sleep patterns, capturing alterations in brain dynamics across multiple disorders. Methods: Using two public datasets (Sleep-EDF and CAP Sleep Database) comprising 200 subjects (112 healthy controls and 88 patients with various sleep pathologies), we computed the fractal scaling of the permutation entropy of these signals. Results: The results demonstrate significantly reduced scaling exponents in pathological sleep compared to healthy controls (mean = 1.24 vs. 1.06, $p<0.001$), indicating disrupted long-range temporal correlations in neural activity. The method achieved 90% classification accuracy for rapid-eye-movement (REM) sleep behavior disorder (F1-score: 0.89) and maintained 74% accuracy when aggregating all pathologies (insomnia, narcolepsy, sleep-disordered breathing, etc.). Conclusions: The advantages of this approach, including compatibility with single-channel EEG (enabling potential wearable applications), independence from sleep-stage annotations, and generalizability across recording montages and sampling rates, stablish a framework for non-specific sleep pathology detection. This is a computationally efficient method that could transform screening protocols and enable earlier intervention. The robustness of this biomarker could enable straightforward clinical applications for common sleep pathologies as well as diseases associated with neurodegenerative conditions. Full article

Hyperechogenicity of the substantia nigra (SN) is observed using transcranial ultrasonography in patients with Parkinson’s Disease. In this study, we investigated whether monogenic forms of PD are more prevalent in these patients and clinically defined their characteristics. Eighty-eight PD patients were part of the analysis. All patients received clinical diagnoses from experienced movement disorder specialists. Each patient underwent transcranial ultrasonography and genetic testing for mutations in the SNCA, PRKN, LRRK2, DJ1, and PINK1 genes. SN hyperechogenicity was identified in 48 patients. Compared to the non-hyperechogenicity group, these patients did not have monogenic forms of PD more frequently, but they did have REM sleep behavior disorder significantly more often, lived in rural areas, and experienced a later age of disease onset. Our study indicated no association between substantia nigra echogenicity and the presence of mutations in the SNCA, LRRK2, DJ1, PRKN, and PINK1 genes. Hyperechogenicity of the substantia nigra, however, remains a common finding in patients with Parkinson’s Disease, correlating with certain features of the disease. Full article

Parkinson’s disease involves widespread neurodegeneration that extends far beyond the basal ganglia, giving rise to a diverse range of non-motor symptoms that frequently emerge before motor onset. These include autonomic dysfunction, cognitive decline, neuropsychiatric disturbances, sleep-related disorders, and sensory deficits. Here, we synthesize current evidence on the anatomical, neurochemical, and network-level mechanisms that drive these symptoms, and we examine how they shape disease progression and clinical heterogeneity. We highlight the limitations of dopamine-centric models and advocate for a framework that treats non-motor symptoms as the disorder’s primary, mechanistically distinct features. We also discuss how emerging technologies—such as multi-omic profiling, artificial intelligence, and network neuroscience—enable earlier identification, stratification of non-motor phenotypes, and the development of precision-based therapeutic strategies. Recognizing non-motor symptoms as central to Parkinson’s disease redefines how the disorder should be diagnosed, studied, and treated. Full article

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsive behavior. In recent years, studies have shown that patients with ADHD often experience sleep problems, raising clinical interest in the potential role of polysomnography (PSG) in the diagnosis and management of ADHD. This study examines polysomnographic findings in children with ADHD who present with diverse sleep complaints. Methods: A cohort of children aged younger than 18 years, diagnosed with ADHD based on DSM-5 criteria, underwent overnight polysomnography. The study assessed various sleep parameters, including sleep latency, sleep efficiency, total sleep time, and the presence of sleep-disordered breathing. Results: A retrospective analysis was conducted on 36 children (29 boys and 7 girls) aged 6 to 14 years, diagnosed with ADHD, who underwent polysomnography between 2021 and 2024. Polysomnographic findings revealed that 77.78% of the children demonstrated significant snoring. Furthermore, 50.0% were diagnosed with obstructive sleep apnea syndrome (OSAS). In addition, eight children exhibited parasomnias. Among them, six had bruxism, three were diagnosed with periodic limb movement disorder (PLMD), and two experienced sleep talking. Other notable sleep-related conditions included two cases of narcolepsy, one case of prolonged sleep onset latency, and one case of central apnea syndrome. Total sleep time (TST) was significantly longer in females compared to males (400.71 ± 32.68 min vs. 361.24 ± 41.20 min, p = 0.0215), whereas rapid eye movement (REM) latency was longer in males compared to females (118.62 ± 55.60 min vs. 78.57 ± 27.82 min, p = 0.0194). These findings highlight the high prevalence of sleep-disordered breathing (SDB) in children with ADHD who present with sleep disturbances. Furthermore, sleep quality, as indicated by longer TST and shorter REM latency, appears to be better in females with ADHD. Conclusions: The findings of this study underscore the critical role of polysomnography (PSG) in the assessment of children with ADHD. PSG provides an objective evaluation of sleep abnormalities commonly associated with ADHD, which may influence symptom manifestation and treatment outcomes. Notably, the results suggest that females with ADHD exhibit better sleep quality, as indicated by longer total sleep time (TST) and shorter rapid eye movement (REM) latency compared to males. We recommend incorporating polysomnography (PSG) into the comprehensive assessment of children with ADHD who present with significant sleep disturbances. Further research is warranted to investigate the impact of targeted interventions for sleep abnormalities on ADHD symptoms, prognosis, and potential sex-specific differences. Full article

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is recognized as a precursor to neurodegenerative diseases. This study aimed to develop predictive models for the timing and subtype of phenoconversion in iRBD. We analyzed comprehensive clinical data from 178 individuals with iRBD over a median follow-up of 3.6 years and applied machine learning models to predict when phenoconversion would occur and whether progression would present with motor- or cognition-first symptoms. During follow-up, 30 patients developed a neurodegenerative disorder, and the extreme gradient boosting survival embeddings–Kaplan neighbors (XGBSE-KN) model demonstrated the best performance for timing (concordance index: 0.823; integrated Brier score: 0.123). Age, antidepressant use, and Movement Disorder Society–Unified Parkinson’s Disease Rating Scale Part III scores correlated with higher phenoconversion risk, while coffee consumption was protective. For subtype classification, the RandomForestClassifier achieved the highest performance (Matthews correlation coefficient: 0.697), indicating that higher Montreal Cognitive Assessment scores and younger age predicted motor-first progression, whereas longer total sleep time was associated with cognition-first outcomes. These findings highlight the utility of machine learning in guiding prognosis and tailored interventions for iRBD. Future research should include additional biomarkers, extend follow-up, and validate these models in external cohorts to ensure generalizability. Full article

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia and abnormal behaviors occurring during REM sleep. Idiopathic RBD (iRBD) is recognized as the strongest prodromal hallmark of α-synucleinopathies, with an established conversion rate to a neurodegenerative condition that reaches up to 96.6% at 15 years of follow-up. Moreover, RBD-converters display a more severe clinical trajectory compared to those that do not present with RBD. However, the extent to which iRBD represents a distinct genetic entity or an early manifestation of neurodegeneration remains unclear. To address this, we applied Genomic Structural Equation Modeling (GenomicSEM) using a GWAS-by-subtraction approach to disentangle the genetic architecture of iRBD from the shared genomic liability across α-synucleinopathies. Our findings highlight the SNCA locus as a key genetic regulator of iRBD susceptibility. While iRBD exhibits a partially distinct genetic signature, residual genomic overlap with neurodegenerative traits suggests that its genetic architecture exists along a continuum of α-synucleinopathy risk. In this scenario, the associations with neuroanatomical correlates may serve as early indicators of a trajectory toward future neurodegeneration. These findings provide a framework for identifying biomarkers that could aid in disease stratification and risk prediction, potentially improving early intervention strategies. Full article

Background/Objectives: Genetic factors play an important role in idiopathic rapid eye movement sleep behavior disorder (iRBD) but have not been fully studied. This study aimed to analyze the Parkinson’s disease (PD)-related genetic loci in iRBD in the southern Chinese population. Methods: In this study, we recruited 292 individuals with PD, 62 with iRBD, and 189 healthy controls (HC). Candidate genes were identified primarily from the Parkinson’s Progression Markers Initiative (PPMI) database. Genotypic and allele frequency analyses were conducted to compare the distribution across HC, iRBD, and PD groups. The effects of significant single-nucleotide polymorphisms (SNPs) on gene expression were examined. Clinical manifestations associated with different genotypes were also analyzed. The receiver operating characteristic (ROC) curve and Kaplan–Meier plots were utilized to further verify the diagnostic and predictive value of these SNPs. Results: We identified two significant SNPs associated with iRBD: rs13294100 of SH3GL2 and rs165599 of COMT. Clinical scale and polysomnography data analysis indicated that iRBD patients with the GA or AA genotype at the COMT rs165599 locus have lower RBDSQ scores and higher sleep efficiency. Moreover, we identified that COMT rs165599 and MCCC1 rs12637471 may play an important role in both PD and iRBD, while SNCA rs356181 was different between iRBD and PD. Conclusions: Our research revealed that in the southern Chinese demographic, genetic loci in SH3GL2 and COMT were linked to iRBD and may act as potential biomarkers for iRBD risk. Additionally, there is evidence suggesting a partial genetic overlap between iRBD and PD, indicating a shared genetic predisposition. Full article