Pseudo[n]-pillar[5]arenes: Synthesis, Structures, and Host-Guest Binding Properties.

[1n]Paracyclophane has been known for nearly 40 years, but its derivatives and properties are understudied in comparison to those of other macrocyclic compounds. By the modification of pillar[5]arene, we successfully obtained five electron-rich pentagonal macrocycles (pseudo[n]-pillar[5]arenes, n = 1-4) with the decrease of substituted phenylenes one after another, achieving the partial derivatization of [15]paracyclophane skeleton at its phenylene sites. Pseudo[n]-pillar[5]arenes (P[n]P[5]s) served as a kind of macrocyclic host to form complexes with various guests, such as dinitriles, dihaloalkanes, and imidazolium salt, in a 1:1 host-guest stoichiometric ratio. The binding constants with the guest gradually reduce along the decrease of substituted phenylene segments from host P[1]P[5] to P[4]P[5]. It is worthy to note that P[n]P[5]s can adjust their conformations to the "pillar-like" shape effectively when binding with succinonitrile in the solid state.

Relationship between sarcopenia and sleep status in female patients with mild to moderate Alzheimer's disease.

BACKGROUND: Sleep disorders and sarcopenia could contribute to the development of Alzheimer's disease (AD), which are risk factors that rapidly deteriorate cognitive functions. However, few studies have evaluated the relationship between sarcopenia and sleep disorders in female AD patients, who have a higher prevalence than male patients. This study aimed to investigate the relationship between sarcopenia and sleep status in female patients with mild to moderate AD. METHODS: This cross-sectional study recruited 112 female outpatients aged between 60 and 85 years. Demographic characteristics, appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were assessed. Sarcopenia was diagnosed according to criteria of the Asian Working Group for Sarcopenia. Pittsburgh Sleep Quality Index (PSQI) assessed sleep variables. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessed cognitive function. Binary logistic regression models explored the relationship between sleep variables and cognitive function and sarcopenia, adjusting for potential cofounders. RESULTS: The outpatients were divided into 36 AD patients with sarcopenia (ADSa) and 76 AD patients without sarcopenia (ADNSa), with a prevalence of 32.1%. ADSa had lower ASMI, weaker grip strength, slower gait speed, a higher incidence of poor sleep quality and poorer cognitive function. Multivariate binary logistic regression analysis showed that high total scores of PSQI (odds ratio (OR) = 1.13), poor sleep quality (OR = 2.73), poor subjective sleep quality (OR = 1.83), low MMSE (OR = 0.77) and MoCA (OR = 0.76) scores were associated with high odds of sarcopenia. Compared to sleep time ≤ 15 min, >60 min (OR = 5.01) were associated with sarcopenia. Sleep duration <6 h (OR = 3.99), 8-9 h (OR = 4.48) and ≥9 h (OR = 6.33) were associated with sarcopenia compared to 7-8 h. CONCLUSIONS: More sleep symptoms and cognitive impairment exist in female patients with sarcopenia. The higher total scores of PSQI, poorer subjective sleep quality, longer sleep latency, excessive and insufficient sleep duration and poorer cognitive function are associated with higher odds of sarcopenia in female patients with mild to moderate AD.

Restless legs syndrome and perceived olfactory and taste dysfunction: A community-based study.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction. METHODS: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history. RESULTS: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases. CONCLUSIONS: RLS was associated with increased odds of perceived olfactory and taste dysfunction.

Bilateral facial colliculus syndrome caused by pontine tegmentum infarction: a case report.

BACKGROUND: Bilateral facial colliculus syndrome is a rare clinical presentation in patient with pontine infarction. We herein described a case of bilateral facial paralysis and complete horizontal gaze palsy possibly caused by paradoxical embolization from patent foramen ovale related stroke. CASE PRESENTATION: A 55-year-old male presented with sudden onset of complete peripheral facial palsy and horizontal gaze palsy after Valsava maneuver. MRI revealed symmetric involvement of bilateral pontine tegmentum in accordance with the location of facial colliculus. CSF analysis and follow-up MRI showed no evidence of central demyelinating disease. Subsequent echocardiography revealed patent foramen ovale and closure surgery was performed. CONCLUSIONS: Facial colliculus syndrome with symmetric dorsal pontine tegmentum involvement may a rare manifestation in posterior circulation stroke.

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BACKGROUND: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. OBJECTIVE: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). METHODS: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. RESULTS: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. CONCLUSION: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis.

BACKGROUND: Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method. METHODS: The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome. CONCLUSIONS: After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.

Synthesis of i-Corona[6]arenes for Selective Anion Binding: Interdependent and Synergistic Anion-π and Hydrogen-Bond Interactions.

i-Corona[3]arene[3]tetrazines were synthesized from the nucleophilic aromatic substitution reaction of resorcinol and its derivatives with 3,6-dichlorotetrazine in a one-pot fashion under mild conditions. All of the resulting macrocycles adopted 1,3,5-alternate conformation irrespective of the nature of the substituents on both upper- and lower-rims. i-Corona[3]arene[3]tetrazine was found to self-regulate its macrocyclic conformation and cavity to recognize anions with binding constants spanning from 26 M-1 to 2.2×103  M-1 depending on the structure of the anions. The selective binding resulted from a significant interdependent and synergistic effect between multiple tetrazine π/anion and Caryl -H/anion hydrogen bond interactions. Taking advantage of synergistic effect revealed, a cyanobenzene-embedded i-corona[3]arene[3]tetrazine was designedly synthesized and highly selective and very strong affinity toward nitrate with a binding constant of 2.2×105  M-1 was achieved.

Modular Strategy for Constructing para-Cage[n]arenes, meta-Cage[n]arenes, and meta-Bimacrocyclic-Arenes.

Here, we present a versatile modular strategy for crafting novel covalent organic cages (para-cage[n]arenes and meta-cage[n]arenes, n = 3,4) and bimacrocycles (meta-bimacrocyclic-arenes) with stable backbones and modifiable rims. These structures can be synthesized from commercially available aromatic multialdehydes in a three-step process: quantitative bromination, Suzuki-Miyaura reaction (yielding over 60%), and a rapid one-pot Friedel-Crafts reaction with paraformaldehyde. Notably, the cage[n]arenes exhibit a well-defined prismatic shape, and the bimacrocyclic-arenes display both dimeric and monomeric configurations.

Macrocycles and Acyclic Cucurbit[n]urils as Pseudo[2]catenane Partners for Long-Acting Neuromuscular Blocks and Rapid Reversal In Vivo.

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.

Higher cortical excitability to negative emotions involved in musculoskeletal pain in Parkinson's disease.

OBJECTIVE: Changes in brain structure and neurotransmitter systems are involved in pain in Parkinson's disease (PD), and emotional factors are closely related to pain. Our study applied electroencephalography (EEG) to investigate the role of emotion in PD patients with chronic musculoskeletal pain. METHODS: Forty-two PD patients with chronic musculoskeletal pain and 38 without were enrolled. EEG data were recorded under resting conditions, and while viewing pictures with neutral, positive, and negative content. We compared spectrum power, functional connectivity, and late positive potential (LPP), an event-related potential (ERP), between the groups. RESULTS: PD patients with pain tended to have higher scores for the Hamilton Rating Scale for Depression (HRSD). In the resting EEG, mean ß-band amplitude was significantly higher in patients with pain than in those without. Logistic regression analysis showed that higher HRSD scores and higher mean ß-band amplitude were associated with pain. ERP analysis revealed that the amplitudes of LPP difference waves (the absolute difference between positive and negative condition LPP and neutral condition LPP) at the central-parietal region were significantly reduced in patients with pain (P = 0.029). Spearman correlation analysis showed that the amplitudes of late (700-1000 ms) negative versus neutral condition LPP difference waves were negatively correlated with pain intensity, assessed by visual analogue scale, (r = -0.393, P = 0.010) and HRSD scores (r = -0.366, P = 0.017). CONCLUSION: Dopaminergic and non-dopaminergic systems may be involved in musculoskeletal pain in PD by increasing ß-band activity and weakening the connection of the θ-band at the central-parietal region. PD patients with musculoskeletal pain have higher cortical excitability to negative emotions. The changes in pain-related EEG may be used as electrophysiological markers and therapeutic targets in PD patients with chronic pain.

miR-29 mediates TGFß1-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts.

TGFß1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR-29 plays an important role in this process. To explore the interactions of miR-29 family members and TGFß1, the effects of transforming growth factor TGFß1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFß1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFß1 caused a decrease in expression of miR-29a/b/c by real-time PCR analysis. TGFß1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFß1-induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFß1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p-PI3K, p-AKT, and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFß1 treatment. The results indicate that TGFß1 beta uses the PI3k-Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K-Akt pathway in IMR90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts.

Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China.

BACKGROUND: Studies suggest seasonal fluctuations of symptoms in Parkinson's disease (PD) patients in Western countries. However, the association between seasonal change and variation in nonmotor symptoms (NMS) in Chinese PD patients is unclear. Here, we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China. METHODS: We studied 1005 PD patients between April 2008 and October 2020. Patients were classified into four seasons according to the 24 Chinese solar terms, based on assessment date. We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity. RESULTS: Among the 1005 patients studied, the mean age was 64.2 ±â€Š9.7 years and 569 (56.6%) of them were men. Relative to the summer group, patients assessed during winter had higher Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction (SCOPA-AUT) scores ( P  = 0.045). The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer ( P  = 0.009). Among patients who completed polysomnography during the same period ( n  = 135), compared with summer follow-ups, we observed a higher percentage of NREMS1 in winter and spring follow-ups ( P  = 0.042, P  = 0.011), a higher NREMS1 time in spring follow-ups ( P  = 0.0024), a lower NREMS2 time in winter follow-ups ( P  = 0.007), and a higher percentage of phasic rapid eye movement (REM)-sleep without atonia in autumn and winter follow-ups ( P  = 0.026 and P  = 0.020, respectively). In a subset of patients with PD and REM sleep behavior disorder (RBD; n  = 182), those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1 (dream-related sub-score) than those visited during summer ( P  = 0.034, P  = 0.020). We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis. CONCLUSIONS: PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter, and less sleep disturbance than those in spring and winter, suggesting that seasonal change and NMS fluctuation are related, especially in patients with early stage PD.

Circadian disruption and sleep disorders in neurodegeneration.

Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.

Prospective study of sleep duration, snoring and risk of heart failure.

OBJECTIVE: To investigate whether nighttime sleep duration and snoring status were associated with incident heart failure (HF). METHODS: A prospective study was conducted based on Kailuan cohort including 93 613 adults free of pre-existing cardiovascular diseases. Sleep duration and snoring status were assessed by self-reported questionnaire. Incident HF cases were ascertained by medical records. Cox proportional hazards model was applied to calculate the HR and 95% CI of risk of developing HF. Mediation analysis was used to understand whether hypertension and diabetes mediated the association between sleep duration, snoring and HF. Data analysis was performed from 1 June 2021 to 1 June 2022. RESULTS: During a median follow-up of 8.8 years, we documented 1343 incident HF cases. Relative to sleep duration of 7.0-7.9 hour/night, short sleep duration was associated with higher risk of developing HF: adjusted HR was 1.24 (95% CI 1.01 to 1.55) for <6 hours/night and 1.29 (95% CI 1.06 to 1.57) for 6.0-6.9 hours/night, after adjustment for potential confounders such as age, sex, smoking, hypertension and diabetes. A similar 20%-30% higher risk of incident HF was found in individuals reporting occasional or frequent snoring relative to never/rare snorers: adjusted HR was 1.32 for occasional snoring (95% CI 1.14 to 1.52) and 1.24 (95% CI 1.06 to 1.46) for frequent snoring. Presence of diabetes significantly mediated the association between both short sleep duration and snoring and HF risk and hypertension significantly mediated the snoring-HF relationship. CONCLUSION: Short sleep duration and snoring were associated with high risk of HF.

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy.

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.

Prediction of the potentially suitable areas of Ligularia virgaurea and Ligularia sagitta on the Qinghai-Tibet Plateau based on future climate change using the MaxEnt model.

Ligularia virgaurea and Ligularia sagitta are two species of poisonous plants with strong invasiveness in natural grasslands in China that have caused considerable harm to animal husbandry and the ecological environment. However, little is known about their suitable habitats and the key environmental factors affecting their distribution. Although some studies have reported the distributions of poisonous plants on the Qinghai-Tibet Plateau (QTP) and predicted their potential distributions at local scales in some regions under climate change, there have been few studies on the widespread distributions of L. virgaurea and L. sagitta. In this study, we recorded 276 and 118 occurrence points of L. virgaurea and L. sagitta on the QTP using GPS, and then used the MaxEnt model to predict the distribution of suitable habitats. Results showed that (1) under current climate conditions, L. virgaurea and L. sagitta are mainly distributed in southern Gansu, eastern Qinghai, northwestern Sichuan, eastern Tibet, and southwestern Yunnan, accounting for approximately 34.9% and 39.8% of the total area of the QTP, respectively; (2) the main environmental variables affecting the distribution of suitable habitats for L. virgaurea and L. sagitta are the Human Footprint Index (52.8%, 42.2%), elevation (11%, 4.4%), soil total nitrogen (18.9%, 4.2%), and precipitation seasonality (5.1%, 7.3%); and (3) in the future, in the 2050s and 2070s, the area of habitat of intermediate suitability for L. virgaurea will spread considerably in northwest Sichuan, while that of high suitability for L. sagitta will spread to eastern Tibet and western Sichuan.

Effects of repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex on excessive daytime sleepiness in patients with Parkinson's disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common sleep disorder in Parkinson's disease (PD), which seriously affects patients' quality of life. Repetitive transcranial magnetic stimulation (rTMS) can be used as an add-on therapy to a variety of non-motor symptoms of PD. However, little is known on the treatment of EDS in PD patients. OBJECTIVE: To explore the effects of low frequency rTMS over right dorsolateral prefrontal cortex (DLPFC) in the treatment of EDS in PD. METHODS: We conducted a sham-controlled, parallel study including 25 individuals of PD with possible EDS based on Epworth Sleepiness Scale (ESS ≥8 points) and randomly divided them into active group (n = 15) and sham group (n = 10). 1 Hz rTMS was administrated over right DLPFC for 10 consecutive days. In the active group, we further classified them into responsive group and non-responsive group according to change of ESS score in comparison with baseline. Clinical assessments on motor and non-motor symptoms were completed at baseline, at the end of treatment and 1 month after treatment. RESULTS: Compared to baseline, active group showed significant improvement on ESS score 10 days and 1 month after treatment (P < 0.05 for both). The percentage change of ESS score was positively related to disease duration during follow-up. No significant changes were observed on ESS score change in the sham group. Further analysis of individuals in the active group showed that, relative to those with non-response to rTMS, individuals with therapeutic response exhibited longer disease duration and lower baseline levodopa equivalent dose. CONCLUSION: Low frequency rTMS over right DLPFC may improve symptoms of EDS in PD.

REM sleep without atonia and vestibular-evoked myogenic potentials: clinical brainstem dysfunction in early-stage Parkinson's disease and isolated REM sleep behavior disorder.

OBJECTIVE: To determine whether the onset of rapid eye movement (REM) sleep behavior disorder (RBD) is associated with changes in brainstem neuronal pathway dysfunction as reflected by vestibular-evoked myogenic potentials (VEMPs) and to evaluate associations between VEMPs and REM sleep without atonia (RSWA) in patients with early-stage Parkinson's disease (PD) and isolated RBD (iRBD). METHODS: Eighty-two early-stage PD patients, 40 iRBD patients, and 41 healthy control individuals underwent one-night video-polysomnography (vPSG) and VEMPs examination. We compared cervical (cVEMP), ocular (oVEMP), and masseter (mVEMP) VEMP parameters among PD with RBD (PD + RBD), PD without RBD (PD-RBD), iRBD, and control groups and analyzed correlations between VEMPs and RSWA in PD and iRBD groups. RESULTS: The PD + RBD group showed delays in bilateral cVEMP (Lp13, Ln23, Rn23: all p < 0.05) and oVEMP (Ln10, Rn10, Rp15: all p < 0.05) peak latencies compared with the PD-RBD group. Total cVEMP scores were higher in the PD + RBD group than in the iRBD group (p = 0.033). In PD patients, phasic RSWA was correlated with total cVEMP scores (p = 0.003), and tonic RSWA was correlated with left oVEMP scores (p = 0.013). CONCLUSIONS: Brainstem neurophysiology as evidenced by altered VEMPs in patients with PD and iRBD could reflect disease evolvement. Moreover, VEMPs alterations may vary depending on the presence of RBD in PD patients. The associations between altered RSWA and VEMP parameters highlight the meaningfulness of detecting brainstem dysfunction in early-stage PD.

Generalized EEG Slowing Across Phasic REM Sleep, Not Subjective RBD Severity, Predicts Neurodegeneration in Idiopathic RBD.

Purpose: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is the prodromal marker of α-synuclein degeneration with markedly high predictive value. We aim to evaluate the value of electroencephalography (EEG) data during rapid eye movement (REM) sleep and subjective RBD severity in predicting the conversion to neurodegenerative diseases in iRBD patients. Methods: At the baseline, iRBD patients underwent clinical assessment and video-polysomnography (PSG). Relative spectral power for nine frequency bands during phasic and tonic REM sleep in three regions of interest, slow-to-fast ratios, clinical and PSG variables were estimated and compared between iRBD patients who converted to neurodegenerative diseases (iRBD-C) and iRBD patients who remained disease-free (iRBD-NC). Receiver operating characteristic (ROC) curves evaluated the predictive performance of slow-to-fast ratios, and subjective RBD severity as assessed with RBD Questionnaire-Hong Kong. Results: Twenty-two (33.8%) patients eventually developed neurodegenerative diseases. The iRBD-C group showed shorter total sleep time (p < 0.001), lower stage 2 sleep percentage (p = 0.044), more periodic leg-movement-related arousal index (p = 0.004), increased tonic chin electromyelographic activity (p = 0.040) and higher REM density in the third REM episode (p = 0.034) than the iRBD-NC group. EEG spectral power analyses revealed that iRBD phenoconverters showed significantly higher delta and lower alpha power, especially in central and occipital regions during the phasic REM state compared to the iRBD-NC group. Significantly higher slow-to-fast ratios were observed in a more generalized way during the phasic state in the iRBD-C group compared to the iRBD-NC group. ROC analyses of the slowing ratio in occipital areas during phasic REM sleep yielded an area under the curve of 0.749 (p = 0.001), while no significant predictive value of subjective RBD severity was observed. Conclusion: Our study shows that EEG slowing, especially in a more generalized manner during the phasic period, may be a promising marker in predicting phenoconversion in iRBD, rather than subjective RBD severity.