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Parkinsonism & Related Disorders Jun 2024Alpha-synucleinopathies are prevalent neurological disorders that cause significant disability, leading to progressive clinical deterioration that is currently managed...
Alpha-synucleinopathies are prevalent neurological disorders that cause significant disability, leading to progressive clinical deterioration that is currently managed solely through symptomatic treatment. Efforts to evaluate disease-modifying therapies during the established stage of the disease have not yielded positive outcomes in terms of clinical or imaging efficacy endpoints. However, alpha-synucleinopathies have a long prodromal phase that presents a promising opportunity for intervention with disease-modifying therapies. The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the most reliable risk factor for identifying individuals in the prodromal stage of alpha-synucleinopathy. This paper discusses the rationale behind targeting idiopathic/isolated RBD in disease-modifying trials and outlines possible study designs, including strategies for patient stratification, selection of biomarkers to assess disease progression and patient eligibility, as well as the identification of suitable endpoints. Additionally, the potential targets for disease-modifying treatment in alpha-synucleinopathies are summarized.
PubMed: 38943771
DOI: 10.1016/j.parkreldis.2024.107042 -
Sleep Jun 2024Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this...
STUDY OBJECTIVES
Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication.
METHODS
Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition.
RESULTS
All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018).
CONCLUSION
Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.
PubMed: 38943546
DOI: 10.1093/sleep/zsae141 -
Trials Jun 2024Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier...
Cognitive training and promoting a healthy lifestyle for individuals with isolated REM sleep behavior disorder: study protocol of the delayed-start randomized controlled trial CogTrAiL-RBD.
BACKGROUND
Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson's disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD.
METHODS
The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD. The intervention consists of a 5-week digital cognitive training accompanied by a module promoting a healthy, active lifestyle. In this monocentric, single-blinded, delayed-start randomized controlled trial, the intervention's effectiveness will be evaluated compared to an initially passive control group that receives the intervention in the second, open-label phase of the study. Eighty individuals with iRBD confirmed by polysomnography will be consecutively recruited from the continuously expanding iRBD cohort at the University Hospital Cologne. The evaluation will focus on cognition and additional neuropsychological and motor variables. Furthermore, the study will examine the feasibility of the intervention, effects on physical activity assessed by accelerometry, and interrogate the intervention's neural effects using magnetic resonance imaging and polysomnography. Besides, a healthy, age-matched control group (HC) will be examined at the first assessment time point, enabling a cross-sectional comparison between individuals with iRBD and HC.
DISCUSSION
This study will provide insights into whether cognitive training and psychoeducation on a healthy, active lifestyle have short- and long-term (neuro-)protective effects for individuals with iRBD.
TRIAL REGISTRATION
The study was prospectively registered in the German Clinical Trial Register (DRKS00024898) on 2022-03-11, https://drks.de/search/de/trial/DRKS00024898 .
PROTOCOL VERSION
V5 2023-04-24.
Topics: Humans; Single-Blind Method; REM Sleep Behavior Disorder; Healthy Lifestyle; Randomized Controlled Trials as Topic; Executive Function; Cognition; Time Factors; Polysomnography; Treatment Outcome; Cognitive Behavioral Therapy; Male; Germany; Middle Aged; Exercise; Female; Aged; Feasibility Studies; Cognitive Training
PubMed: 38943191
DOI: 10.1186/s13063-024-08265-9 -
The Lancet. Neurology Jun 2024Sleep disorders are common in people with Parkinson's disease. These disorders, which increase in frequency throughout the course of the neurodegenerative disease and... (Review)
Review
Sleep disorders are common in people with Parkinson's disease. These disorders, which increase in frequency throughout the course of the neurodegenerative disease and impair quality of life, include insomnia, excessive daytime sleepiness, circadian disorders, obstructive sleep apnoea, restless legs syndrome, and rapid eye movement (REM) sleep behaviour disorder. The causes of these sleep disorders are complex and multifactorial, including the degeneration of the neural structures that modulate sleep, the detrimental effect of some medications on sleep, the parkinsonian symptoms that interfere with mobility and comfort in bed, and comorbidities that disrupt sleep quality and quantity. The clinical evaluation of sleep disorders include both subjective (eg, questionnaires or diaries) and objective (eg, actigraphy or video polysomnography) assessments. The management of patients with Parkinson's disease and a sleep disorder is challenging and should be individualised. Treatment can include education aiming at changes in behaviour (ie, sleep hygiene), cognitive behavioural therapy, continuous dopaminergic stimulation at night, and specific medications. REM sleep behaviour disorder can occur several years before the onset of parkinsonism, suggesting that the implementation of trials of neuroprotective therapies should focus on people with this sleep disorder.
PubMed: 38942041
DOI: 10.1016/S1474-4422(24)00170-4 -
IEEE Transactions on Neural Systems and... Jun 2024Sleep quality is an essential parameter of a healthy human life, while sleep disorders such as sleep apnea are abundant. In the investigation of sleep and its...
Sleep quality is an essential parameter of a healthy human life, while sleep disorders such as sleep apnea are abundant. In the investigation of sleep and its malfunction, the gold-standard is polysomnography, which utilizes an extensive range of variables for sleep stage classification. However, undergoing full polysomnography, which requires many sensors that are directly connected to the heaviness of the setup and the discomfort of sleep, brings a significant burden. In this study, sleep stage classification was performed using the single dimension of nasal pressure, dramatically decreasing the complexity of the process. In turn, such improvements could increase the much needed clinical applicability. Specifically, we propose a deep learning structure consisting of multi-kernel convolutional neural networks and bidirectional long short-term memory for sleep stage classification. Sleep stages of 25 healthy subjects were classified into 3-class (wake, rapid eye movement (REM), and non-REM) and 4-class (wake, REM, light, and deep sleep) based on nasal pressure. Following a leave-one-subject-out cross-validation, in the 3-class the accuracy was 0.704, the F1-score was 0.490, and the kappa value was 0.283 for the overall metrics. In the 4-class, the accuracy was 0.604, the F1-score was 0.349, and the kappa value was 0.217 for the overall metrics. This was higher than the four comparative models, including the class-wise F1-score. This result demonstrates the possibility of a sleep stage classification model only using easily applicable and highly practical nasal pressure recordings. This is also likely to be used with interventions that could help treat sleep-related diseases.
PubMed: 38941194
DOI: 10.1109/TNSRE.2024.3420715 -
Frontiers in Sleep 2024Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with...
INTRODUCTION
Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5-4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance.
METHODS
Participants were adults ages 55-80 with diary-reported sleep efficiency <90% and wake after sleep onset (WASO) >20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention ( = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing.
RESULTS
Subjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5-4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention.
CONCLUSION
A TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.
PubMed: 38938690
DOI: 10.3389/frsle.2023.1265006 -
Journal of Sleep Research Jun 2024Laboratory polysomnography provides gold-standard measures of sleep physiology, but multi-night investigations are resource intensive. We assessed the night-to-night...
Laboratory polysomnography provides gold-standard measures of sleep physiology, but multi-night investigations are resource intensive. We assessed the night-to-night stability via reproducibility metrics for sleep macrostructure and electroencephalography oscillations in a group of cognitively normal adults attending two consecutive polysomnographies. Electroencephalographies were analysed using an automatic algorithm for detection of slow-wave activity, spindle and K-complex densities. Average differences between nights for sleep macrostructure, electroencephalography oscillations and sleep apnea severity were assessed, and test-retest reliability was determined using two-way intraclass correlations. Agreement was calculated using the smallest real differences between nights for all measures. Night 2 polysomnographies showed significantly greater time in bed, total sleep time (6.3 hr versus 6.8 hr, p < 0.001) and percentage of rapid eye movement sleep (17.5 versus 19.7, p < 0.001). Intraclass correlations were low for total sleep time, percentage of rapid eye movement sleep and sleep efficiency, moderate for percentage of slow-wave sleep and percentage of non-rapid eye movement 2 sleep, good for slow-wave activity and K-complex densities, and excellent for spindles and apnea-hypopnea index with hypopneas defined according to 4% oxygen desaturation criteria only. The smallest real difference values were proportionally high for most sleep macrostructure measures, indicating moderate agreement, and proportionally lower for most electroencephalography microstructure variables. Slow waves, K-complexes, spindles and apnea severity indices are highly reproducible across two consecutive nights of polysomnography. In contrast, sleep macrostructure measures all demonstrated poor reproducibility as indicated by low intraclass correlation values and moderate agreement. Although there were average differences in percentage of rapid eye movement sleep and total sleep time, these were numerically small and perhaps functionally or clinically less significant. One night of in-laboratory polysomnography is enough to provide stable, reproducible estimates of an individual's sleep concerning measures of slow-wave activity, spindles, K-complex densities and apnea severity.
PubMed: 38937887
DOI: 10.1111/jsr.14281 -
PloS One 2024Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion...
Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion maps for a more accurate detection of respiratory arrest points. Conventional change-point detection methods are limited when dealing with complex nonlinear data structures, and the proposed method overcomes these limitations. The proposed method embeds subsequence data in a low-dimensional space while considering the global and local structures of the data and uses the distance between the data as the score of the change point. Experiments using synthetic and real-world contact-free sensor data confirmed the superiority of the proposed method when dealing with noise, and it detected apnea events with greater accuracy than conventional methods. In addition to improving sleep monitoring, the proposed method can be applied in other fields, such as healthcare, manufacturing, and finance. This study will contribute to the development of advanced monitoring systems that adapt to diverse conditions while protecting privacy.
Topics: Humans; Sleep Apnea Syndromes; Polysomnography; Algorithms; Monitoring, Physiologic
PubMed: 38935677
DOI: 10.1371/journal.pone.0306139 -
Journal of Clinical Sleep Medicine :... Jun 2024Postoperative respiratory adverse events (PRAE) occurred more frequently in children having adenotonsillectomy than the general surgical population, and can require...
STUDY OBJECTIVES
Postoperative respiratory adverse events (PRAE) occurred more frequently in children having adenotonsillectomy than the general surgical population, and can require escalation of care. This study aims to assess the usefulness of post-induction fentanyl-test to predict PRAE in children with obstructive sleep apnea (OSA) after adenotonsillectomy.
METHODS
Two hundred and forty patients with OSA undergoing adenotonsillectomy were included in this study. The oxygen saturation during sleep was monitored the night before adenotonsillectomy. Fentanyl-test was conducted under spontaneous breath after anesthesia induction with sevoflurane. Fentanyl-induced reduction in respiratory rate (FRR) was defined as the percentage of reduction in respiratory rate after 1 mcg/kg fentanyl administration. PRAE in the post-anesthesia care unit (PACU) included both respiratory complications and medical interventions. Receiver operating characteristic (ROC) analysis was used to assess the usefulness of fentanyl-test in predicting PRAE.
RESULTS
Of the 240 children undergoing elective adenotonsillectomy, 38 children (16%) experienced PRAE in PACU. The areas under ROC curve for FRR and Nadir SpO were 0.756 and 0.692, respectively. FRR greater than 53% best predicted PRAE in PACU, with a sensitivity of 68% and a specificity of 72%. Patients with FRR > 53% exhibited a significantly longer duration of desaturation requiring supplementary oxygen than those with FRR ≦ 53% (p < 0.001).
CONCLUSIONS
We suggest that post-induction fentanyl-test is a feasible evaluation for children undergoing adenotonsillectomy to predict early PRAE, especially for those who have not undergone polysomnography.
CLINICAL TRIAL REGISTRATION
Registry: ClinicalTrials.gov; Name: Effects of Individualized Opioid Analgesia Versus Conventional Opioid Analgesia After Adenotonsillectomy in Children; URL: https://clinicaltrials.gov/study/NCT04527393; Identifier: NCT04527393.
PubMed: 38935059
DOI: 10.5664/jcsm.11262 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of...
OBJECTIVE
Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of automatic positive pressure in the airways therapy (aPAP therapy) in patients with obstructive sleep apnea syndrome (OSA).
MATERIAL AND METHODS
59 men participated in the study, the average age was 51.9±2.4 years. The main group (MG1) consisted of 30 patients with a verified diagnosis of moderate OSA. 29 men of comparable age and body weight made up the control group (CG) without an objectively confirmed diagnosis of OSA. After the stage of introduction into the study, the type of respiratory support with individual pressure settings was selected for patients with MG1. After 6 months of aPAP therapy with high compliance (at least 85%), the same patients who made up MG2 after treatment underwent repeated polysomnography (PSG) and the GDF 15 content was evaluated. Methods: questionnaire, examination, polysomnography, enzyme immunoassay of blood serum to determine the content of GDF 15.
RESULTS
A 6-month course of aPAP therapy with a high degree of compliance significantly improved the sleep structure and breathing pattern: the representation of NREM 3 increased from 79.2±15.6 to 102.6±21.6 minutes and the REM phase from 56.9± 13.6 to 115.6±26.8. Episodes of apnea were eliminated - apnea-hypopnea index decreased from 21.1 [17.3; 39.1] to 2.5 [1.8; 4.6] and the average values of SaO increased from 85.9% to 91.5%. At the same time, a statistically significant excess of GDF 15 was revealed in MG1 - 20.4 [14.16; 31.71] and MG2 - 17.2 [13.63; 24.44]) in comparison with CG - 13.65 [10.7; 17.09]. Despite the lack of statistical significance, a change in the level of GDF 15 was revealed in the form of a decrease in its concentration after a 6-month course of aPAP therapy.
CONCLUSION
A 6-month course of aPAP therapy made it possible to eliminate intermittent nocturnal hypoxia and improve sleep structure in patients with OSA, as well as reduce the content of GDF 15 protein in blood serum in patients with OSA. However, the tendency to decrease the content of this protein, despite the lack of statistical reliability, confirms the effectiveness of OSA therapy and the possibility of preventing early and pathological aging from the standpoint of somnology and molecular biogerontology.
Topics: Humans; Male; Middle Aged; Growth Differentiation Factor 15; Pilot Projects; Sleep Apnea, Obstructive; Polysomnography; Continuous Positive Airway Pressure; Sleep Apnea Syndromes; Adult
PubMed: 38934676
DOI: 10.17116/jnevro2024124052118