Associations between insomnia and large vessel occlusion acute ischemic stroke: An observational study.

OBJECTIVES: This study explored the association between insomnia and the clinical outcome of large vessel occlusion Acute Ischemic Stroke (AIS) and attempted to explore its potential mechanisms from the perspectives of inflammation and oxidative stress. METHODS: AIS patients who underwent endovascular treatment for large vessel occlusion at Binzhou Central Hospital from 2018 to 2022 (n = 508) were included. Patients were divided into an insomnia group and a non-insomnia group. Insomnia was judged by self-reported Athens Insomnia Scale score. Regression analysis was used to compare the differences in the 24-hour and 7-day National Institutes of Health Stroke Scale (NIHSS) score, Early Neurological Deterioration (END), early adverse event incidence, 90-day prognosis and mortality, and serum biomarkers levels. RESULTS: The incidence of insomnia in the study population was 39.6% (n = 144, insomnia group; n = 364, non-insomnia group). Compared with the non-insomnia group, a worse prognosis outcome (63% vs. 49%, adjusted rate ratio: 1.8, 95% Confidence Interval: 1.2-3.7; p = 0.016), higher 24-h and 7-day NIHSS score (17 [9-36] vs. 13 [5-20]; p = 0.024, and 11 [4‒24) vs. 8 [2‒14]; p = 0.031, respectively), higher END (24% vs. 15%, p = 0.022), and higher incidence of adverse events were observed in the insomnia group (79% vs. 59%, p = 0.010). The 90-day mortality was higher in the insomnia group than that in the non-insomnia group (22% vs. 17%), however, such a difference was not statistically significant. CONCLUSION: Insomnia is closely related to the clinical outcome of AIS with large vessel occlusion, and inflammation and oxidative stress mechanisms may be involved.

Cortical connectivity of cholinergic basal forebrain in Parkinson's disease with mild cognitive impairment.

Background: Cholinergic basal forebrain (BF) pathology is a hallmark of Parkinson's disease (PD) with mild cognitive impairment (PD-MCI). Assessment of functional connectivity (FC) of different cholinergic BF nuclei may deepen the understanding of PD-MCI pathogenesis. Methods: Seed-based FC analysis was performed with bilateral medial septal nucleus, the nucleus of the vertical limb of the diagonal band, nucleus of the horizontal limb of the diagonal band (Ch1-3), and the nucleus basalis of Meynert (NBM/Ch4) to explore the BF functional alterations in different frequency bands. Correlations between FC values of abnormal regions and scores of cognitive domains and depression in the PD group were also assessed. Results: For the right Ch4, in the conventional frequency band, the PD-MCI group exhibited lower FC values in the right middle cingulate and paracingulate gyri, middle frontal gyrus, left inferior parietal gyrus, and superior frontal gyrus compared with healthy controls (HC), and in the left calcarine fissure and surrounding cortex compared with PD with normal cognition (PD-NC). For the slow 4 subbands, the PD-MCI group showed significantly lower FC values in the left putamen, middle frontal gyrus, right middle frontal gyrus, and precuneus compared with HC, and in right middle frontal gyrus cingulate and paracingulate gyri compared with the PD-NC group. For the slow 5 subbands, the PD-MCI group showed increased FC values in the right calcarine fissure and surrounding cortex, and left cerebellum. For the left Ch1-3, FC values in the right middle cingulate and paracingulate gyri were lower in patients with PD-MCI than in the PD-NC group in slow 4 subbands. Furthermore, altered FC values in the cortical regions for Ch4 seed were possibly correlated with depression and different cognitive domain scores. Conclusions: The study identified an imbalanced association between different cholinergic BF nuclei and cortical regions in patients with PD-MCI, and showed that FC changes are frequency-specific, which may provide new insights into functional alterations within the cholinergic system in cognitive impairment associated with PD.

Associations between insomnia and large vessel occlusion acute ischemic stroke: An observational study

Abstract Objectives: This study explored the association between insomnia and the clinical outcome of large vessel occlusion Acute Ischemic Stroke (AIS) and attempted to explore its potential mechanisms from the perspectives of inflammation and oxidative stress. Methods: AIS patients who underwent endovascular treatment for large vessel occlusion at Binzhou Central Hospital from 2018 to 2022 (n = 508) were included. Patients were divided into an insomnia group and a non-insomnia group. Insomnia was judged by self-reported Athens Insomnia Scale score. Regression analysis was used to compare the differences in the 24-hour and 7-day National Institutes of Health Stroke Scale (NIHSS) score, Early Neurological Deterioration (END), early adverse event incidence, 90-day prognosis and mortality, and serum bio-markers levels. Results: The incidence of insomnia in the study population was 39.6% (n = 144, insomnia group; n = 364, non-insomnia group). Compared with the non-insomnia group, a worse prognosis outcome (63% vs. 49%, adjusted rate ratio: 1.8, 95% Confidence Interval: 1.2-3.7; p = 0.016), higher 24-h and 7-day NIHSS score (17 [9-36] vs. 13 [5-20]; p = 0.024, and 11 [4‒24) vs. 8 [2‒14]; p = 0.031, respectively), higher END (24% vs. 15%, p = 0.022), and higher incidence of adverse events were observed in the insomnia group (79% vs. 59%, p = 0.010). The 90-day mortality was higher in the insomnia group than that in the non-insomnia group (22% vs. 17%), however, such a difference was not statistically significant. Conclusion: Insomnia is closely related to the clinical outcome of AIS with large vessel occlusion, and inflammation and oxidative stress mechanisms may be involved.

Metabolite changes in prefrontal lobes and the anterior cingulate cortex correlate with processing speed and executive function in Parkinson disease patients.

Background: Processing speed and executive function can be impaired in patients with Parkinson disease (PD). However, the neural factors related to the slowdown in processing speed and dysexecutive function in PD are not completely understood. The objective of this study is to investigate the metabolic changes of the frontal and anterior cingulate cortex (ACC) through the use of 1H magnetic resonance spectroscopy and to explore the association between cognitive function and metabolic ratios. Methods: In this retrospective case-control study, we conducted neuropsychological assessments of executive function and information processing speed in healthy controls (HCs) and in patients with PD. Chemical information was obtained for the of N-acetyl-aspartate (NAA):creatine (Cr) ratio and the choline-containing compounds (Cho):Cr ratio within the bilateral prefrontal cortex and ACC. Using hierarchical multiple regression analysis, we analyzed the relationship between cognitive function and metabolic ratios in the bilateral prefrontal lobe and ACC in patients with PD. Results: In all, 59 patients with PD and 30 HCs were recruited. Patients with PD showed worse performance in executive function and processing speed compared with HCs (P<0.001). In patients with PD, the Cho:Cr ratios in the ACC (Z=2.20, P=0.028) and the right prefrontal cortex (t=2.16, P=0.034) were significantly increased. The hierarchical multiple regressions in patients with PD showed that the NAA:Cr ratio in the ACC correlated with the Stroop A completion times (P<0.05) and that the NAA:Cr ratio of the right prefrontal cortex correlated with the scores of the Wechsler Adult Intelligence Scale (WAIS)-Digit symbol test (P<0.05). Conclusions: Information processing speed and executive function are impaired in patients with PD. Neuronal integrity and membrane turnover in the ACC and the right prefrontal cortex may be important factors in the slowdown of the information processing speed in patients with PD.

Abnormal Neural Activity in Different Frequency Bands in Parkinson's Disease With Mild Cognitive Impairment.

Background: Abnormal spontaneous neural activity is often found in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps. Methods: Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups. Results: In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III). Conclusion: Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI.

Meynert nucleus-related cortical thinning in Parkinson's disease with mild cognitive impairment.

BACKGROUND: Cognitive impairment in Parkinson's disease (PD) involves the cholinergic system and cholinergic neurons, especially the nucleus basalis of Meynert (NBM/Ch4) located in the basal forebrain (BF). We analyzed associations between NBM/Ch4 volume and cortical thickness to determine whether the NBM/Ch4-innervated neocortex shows parallel atrophy with the NBM/Ch4 as disease progresses in PD patients with cognitive impairment (PD-MCI). METHODS: We enrolled 35 PD-MCI patients, 48 PD patients with normal cognition (PD-NC), and 33 age- and education-matched healthy controls (HCs), with all participants undergoing neuropsychological assessment and structural magnetic resonance imaging (MRI). Correlation analyses between NBM/Ch4 volume and cortical thickness and correlation coefficient comparisons were conducted within and across groups. RESULTS: In the PD-MCI group, NBM/Ch4 volume was positively correlated with cortical thickness in the bilateral posterior cingulate, parietal, and frontal and left insular regions. Based on correlation coefficient comparisons, the atrophy of NBM/Ch4 was more correlated with the cortical thickness of right posterior cingulate and precuneus, anterior cingulate and medial orbitofrontal lobe in PD-MCI versus HC, and the right medial orbitofrontal lobe and anterior cingulate in PD-NC versus HC. Further partial correlations between cortical thickness and NBM/Ch4 volume were significant in the right medial orbitofrontal (PD-NC: r=0.3, P=0.045; PD-MCI: r=0.51, P=0.003) and anterior cingulate (PD-NC: r=0.41, P=0.006; PD-MCI: r=0.43, P=0.013) in the PD groups and in the right precuneus (r=0.37, P=0.04) and posterior cingulate (r=0.46, P=0.008) in the PD-MCI group. CONCLUSIONS: The stronger correlation between NBM/Ch4 and cortical thinning in PD-MCI patients suggests that NBM/Ch4 volume loss may play an important role in PD cognitive impairment.

Different iron deposition patterns in Parkinson's disease subtypes: a quantitative susceptibility mapping study.

BACKGROUND: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with various subtypes and uncertain pathogenesis. Iron deposition is considered to be involved in the pathological mechanisms of PD. The present study aimed to investigate the iron deposition in deep gray matter in patients with different PD subtypes using quantitative susceptibility mapping (QSM). METHODS: Forty-six PD patients and 22 healthy controls (HCs) were recruited for the study. PD patients were allocated to the tremor-dominant (TD) group (n=22), postural instability and gait disorder-dominant (PIGD) group (n=19), and intermediate group (n=5). Susceptibility values in deep gray matter nuclei measured by QSM among the PD-TD and PD-PIGD groups and the HCs, as well as the relationship between iron accumulation and clinical motor features, were investigated. RESULTS: Susceptibility values in the dentate nucleus (DN) were greater in the PD-TD (118.73±70.45) group than in the PD-PIGD (72.14±39.85, P=0.02) group and HCs (78.26±41.38, P=0.042). Further, a significant positive correlation was observed between the DN susceptibility values and tremor scores (r=0.324, P=0.028). Compared with the HCs (182.60±85.35), both the PD-TD (282.00±102.49, P=0.006) and PD-PIGD groups (284.91±118.54, P=0.007) exhibited greater susceptibility values in the substantia nigra (SN) pars reticulata. The susceptibility values in the SN pars compacta were also greater in the PD-PIGD group (164.51±89.44) than in the HCs (107.78±63.11, P=0.048). CONCLUSIONS: The present study demonstrated various iron deposition patterns in different PD phenotypes. These findings give insight into the pathophysiology underlying different PD phenotypes, and potentially illustrate the involvement of iron deposition in the PD-TD and PD-PIGD subtypes.

An SBM-based machine learning model for identifying mild cognitive impairment in patients with Parkinson's disease.

OBJECTIVE: To identify Parkinson's disease with mild cognitive impairment (PD-MCI) through surface-based morphometry (SBM) based machine learning model. METHODS: 93 patients with parkinson's disease (35 PD with normal cognition, 58 PD-MCI) were examined, obtaining 276 SBM variables per subject. 20 healthy control subjects were used as the reference. After extracting features with statistically significance, support vector machine (SVM) model with grid search method was applied to identify patients with PD-MCI. Accuracy, matthews correlation coefficient (MCC), receiver operating characteristic curve (ROC), precision-recall curve (PR), AUC-ROC, AUC-PR and leave-one-out cross validation (LOOCV) strategy were employed for model evaluation. RESULTS: PD-MCI is characterized by widespread structural abnormality. SVM model with SBM features achieved an accuracy of 80.00% and area under the ROC of 0.86 for identifying PD-MCI. MCC, AUC-PR, and LOOCV classification accuracy were 0.56, 0.89, and 78.08%, respectively. CONCLUSION: Automatic identification of PD-MCI could be realized by SBM-based machine learning model.

Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials.

BACKGROUND: Several recent randomized clinical trials have preliminarily demonstrated that initial targeted therapy with combined BRAF and MEK inhibition is more effective in metastatic melanoma (MM) than single agent. To guide therapeutic decisions, we did a comprehensive network meta-analysis to identify evidence to robustly support whether combined BRAF and MEK inhibition is the best initial targeted therapeutic strategy for patients with MM. METHODS: The databases of PubMed and trial registries were researched for randomized clinical trials of targeted therapy. Data of outcome were extracted on progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Network meta-analysis using a Bayesian statistical model was performed to evaluate relative hazard ratio (HR) for PFS and OS, odds ratio (OR) for ORR. RESULTS: Finally, 16 eligible trials comprising 5976 participants were included in this meta-analysis. PFS were significantly prolonged in patients who received combined BRAF-MEK inhibition compared with those who received BRAF inhibition (HR: 0.58, 95%CI: 0.51-0.67, P < 0.0001) or MEK inhibition alone (HR: 0.29, 95%CI: 0.22-0.37, P < 0.0001). Combined BRAF-MEK inhibition also improved the OS over BRAF inhibition (HR: 0.67, 95%CI: 0.56-0.81, P < 0.0001) or MEK inhibition alone (HR: 0.48, 95%CI: 0.36-0.65, P < 0.0001). The ORR was superior in combined BRAF and MEK inhibition comparing with BRAF inhibition (OR: 2.00, 95%CI: 1.66-2.44, P < 0.0001) or MEK inhibition alone (OR: 20.66, 95%CI: 12.22-35.47, P < 0.0001). CONCLUSIONS: This study indicates that concurrent inhibition of BRAF and MEK improved the most effective therapeutic modality as compared as single BRAF or MEK inhibition for patients with MM.