Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166070 | GEO | 2024/01/16
REPOSITORIES: GEO
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Project description:Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease
| PRJNA699177 | ENA
Project description:Parkinson's disease (PD) lacks reliable, non-invasive biomarker tests for early intervention and management. Thus, a minimally invasive test for the early detection and monitoring of PD and REM sleep behavior disorder (iRBD) is a highly unmet need for developing drugs and planning patient care. Extracellular vehicles (EVs) are found in a wide variety of biofluids, including plasma. EV-mediated functional transfer of microRNAs (miRNAs) may be viable candidates as biomarkers for PD and iRBD. Next-generation sequencing (NGS) of EV-derived small RNAs was performed in 60 normal controls, 56 iRBD patients and 53 PD patients to profile small non-coding RNAs (sncRNAs). Moreover, prospective follow-up was performed for these 56 iRBD patients for an average of 3.3 years. Full-scale miRNA profiles of plasma EVs were evaluated by machine-learning methods. After optimizing the library construction method for low RNA inputs (named EVsmall-seq), we built a machine learning algorithm that identified diagnostic miRNA signatures for distinguishing iRBD patients (AUC 0.969) and PD patients (AUC 0.916) from healthy individuals; and PD patients (AUC 0.929) from iRBD patients. We illustrated all the possible expression patterns across healthy-iRBD-PD hierarchy. We also showed 20 examples of miRNAs with consistently increasing or decreasing expression levels from controls to iRBD to PD. In addition, four miRNAs were found to be correlated with iRBD conversion. Distinct characteristics of the miRNA profiles among normal, iRBD and PD samples were discovered, which provides a panel of promising biomarkers for the identification of PD patients and those in the prodromal stage iRBD.
| S-EPMC10781790 | biostudies-literature
Project description:Background and purpose: Growing evidence suggests that Machine Learning (ML) models can assist the diagnosis of neurological disorders. However, little is known about the potential application of ML in diagnosing idiopathic REM sleep behavior disorder (iRBD), a parasomnia characterized by a high risk of phenoconversion to synucleinopathies. This study aimed to develop a model using ML algorithms to identify iRBD patients and test its accuracy. Methods: Data were acquired from 32 participants (20 iRBD patients and 12 controls). All subjects underwent a video-polysomnography. In all subjects, we measured the components of heart rate variability (HRV) during 24 h recordings and calculated night-to-day ratios (cardiac autonomic indices). Discriminating performances of single HRV features were assessed. ML models based on Logistic Regression (LR), Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) were trained on HRV data. The utility of HRV features and ML models for detecting iRBD was evaluated by area under the ROC curve (AUC), sensitivity, specificity and accuracy corresponding to optimal models. Results: Cardiac autonomic indices had low performances (accuracy 63-69%) in distinguishing iRBD from control subjects. By contrast, the RF model performed the best, with excellent accuracy (94%), sensitivity (95%) and specificity (92%), while XGBoost showed accuracy (91%), specificity (83%) and sensitivity (95%). The mean triangular index during wake (TIw) was the best discriminating feature between iRBD and HC, with 81% accuracy, reaching 84% accuracy when combined with VLF power during sleep using an LR model. Conclusions: Our findings demonstrated that ML algorithms can accurately identify iRBD patients. Our model could be used in clinical practice to facilitate the early detection of this form of RBD.
| S-EPMC9689751 | biostudies-literature
Project description:ObjectiveNightmare disorder consists of the appearance of unpleasant and vivid, repeated dreams, with a situation of discomfort and anguish on awakening. Its prevalence is 3%-4% in adults. They do not associate muscle mobilization during this phase. REM sleep behavior disorder (RSBD) is a rare parasomnia (0.5% of people older than 60 years of age), characterized by the presence of unpleasant dreams, with violent content, and vigorous movements of limbs (kicks and punches), reflecting a loss of muscle atony typical of the REM phase of sleep. Language (screams and words) can also be emitted. The same clinical manifestations of RSBD can appear in other sleep disorders. The diagnosis requires the performance of a polysomnography.MethodsWe present the case of a 41-year-old man referred for vivid and unpleasant dreams, beginning in the last year, related to work stress.ResultsThe polysomnography showed the loss of atony in the REM phase and emission of a prolonged howl after which the patient continues in the REM phase.DiscussionProlonged howling is a very rare symptom in sleep disorders, and very atypical in RSBD, so polysomnography is essential to confirm the diagnosis and rule out other parasomnias.
| S-EPMC9987201 | biostudies-literature
Project description:Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to ?-synuclein-dependent degeneration in RBD patients.
| S-EPMC5799338 | biostudies-literature
Project description:Study objectivesREM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD.DesignWe comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables.SettingTertiary-care sleep center.ParticipantsParticipants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls.InterventionsN/A.Measurements and resultsRSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01).ConclusionsAntidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD.
| S-EPMC4434557 | biostudies-literature
Project description:As factors associated with injury in rapid eye movement (REM) sleep behavior disorder (RBD) remain largely unknown, we aimed to identify such factors.We surveyed consecutive idiopathic (iRBD) or symptomatic RBD patients seen between 2008 and 2010 regarding RBD-related injuries. Associations between injuries and clinical variables were determined with odds ratios (OR) and multiple logistic regression analyses. The primary outcome variables were injury and injury severity.Fifty-three patients (40%) responded. Median age was 69?years, and 35 (73.5%) were men. Twenty-eight (55%) had iRBD. Twenty-nine (55%) reported injury, with 37.8% to self and 16.7% to the bed partner. 11.3% had marked injuries requiring medical intervention or hospitalization, including two (4%) subdural hematomas. iRBD diagnosis (OR = 6.8, p = 0.016) and dream recall (OR = 7.5, p = 0.03) were associated with injury; and iRBD diagnosis was independently associated with injury and injury severity adjusting for age, gender, DEB frequency, and duration. Falls (p = 0.03) were also associated with injury severity. DEB frequency was not associated with injury, injury severity, or falls.Injuries appear to be a frequent complication of RBD, although the relatively low response rate in our survey could have biased results. iRBD patients are more likely to suffer injury--and more severe injuries--than symptomatic RBD patients. In addition, recall of dreams was also associated with injury, and dream enactment behavior (DEB)-related falls were associated with more severe injuries. One in nine patients suffered injury requiring medical intervention. The frequency of DEB did not predict RBD-related injuries, highlighting the importance of timely initiation of treatment for RBD in patients having even rare DEB episodes. Future prospective studies will be necessary to define predictors of injury in RBD.
| S-EPMC4253642 | biostudies-literature
Project description:ObjectiveTo determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion.MethodsFor this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values.ResultsPDRP expression was elevated in both groups of subjects with RBD (cohort 1: p < 0.04; cohort 2: p < 0.005). Of the 17 subjects with long-term follow-up, 8 were diagnosed with Parkinson disease or dementia with Lewy bodies; the others did not phenoconvert. For individual subjects with RBD, final phenoconversion status was predicted using a logistical regression model based on PDRP expression and subject age at the time of imaging (r(2) = 0.64, p < 0.0001).ConclusionsLatent network abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.
| S-EPMC3963420 | biostudies-literature
Project description:OBJECTIVE:To examine how urate concentrations are related to the risk of having possible REM sleep behavior disorder (pRBD) in a community-based cohort. METHODS:The study included 12,923 Chinese adults of the Kailuan Study, free of Parkinson disease (PD) and dementia. Plasma urate concentrations were measured in 2006, 2008, and 2010. Cumulative average urate concentration was used as primary exposure. In 2012, we determined pRBD status using a validated RBD questionnaire-Hong Kong (RBDQ-HK). Logistic regression analysis was performed to estimate the association between urate concentrations during 2006-2010 and odds of having pRBD in 2012 or pRBD case with symptom onset within 1 year. RESULTS:Higher average urate concentrations were associated with a lower odds of pRBD (P-trend <0.001). The adjusted odds ratio (OR), for the highest versus lowest urate quintiles, was 0.43 (95% confidence intervals (CIs) 0.32-0.57). Significant association was consistently observed when we examined the association of a single urate assessment (2006 or 2010) or the rate of change in urate concentrations during 2006-2010 with pRBD (P-trend <0.001 for all). However, restricting to pRBD onset during 2011-2012, we observed a nonsignificant trend between high urate concentration and high odds of pRBD (P-trend = 0.09). INTERPRETATION:Higher average urate concentrations were associated with a lower likelihood of having pRBD, but not new-onset pRBD. Because of its observational study design, the result should be interpreted with caution due to the possibility of residual confounding.
| S-EPMC6917330 | biostudies-literature
Project description:Non-motor symptoms can be present in essential tremor (ET). We intend to assess the frequency of rapid eye movement (REM) sleep behavior disorder (RBD) and dysautonomic symptoms in ET patients and evaluate the differences between patients with ET and RBD (ET-RBD and ET without RBD [ET-nonRBD]).All ET patients were contacted by telephone. Autonomic symptoms were assessed using the Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) questionnaire, and RBD symptoms with the RBD screening questionnaire (RBDSQ) using ≥5 as a cut-off for probable RBD (pRBD).From 92 ET patients contacted, 53 (55% female) were included. The mean age at assessment was 73.6±19 years, and the average disease duration was 19.9±17.3 years. Fourteen patients (26.4%) had pRBD and 52 (98.1%) reported at least one autonomic symptom, the most prevalent being urinary symptoms (96%). The ET-RBD group had higher SCOPA-total and thermoregulatory scores than ET-nonRBD patients (13.9±9.6 vs. 7.7±5.1, p=0.017 and 2.5±2.0 vs. 0.9±1.6, p=0.001). There were no other differences between groups.Our results suggest that pRBD is common in ET, and its presence is associated with dysautonomic symptoms. As these symptoms are known to be prodromal symptoms of Parkinson's disease (PD), we question if this patient subgroup has a higher risk of developing a synucleinopathy.
| S-EPMC5840316 | biostudies-other