Correlation of glymphatic system abnormalities with Parkinson's disease progression: a clinical study based on non-invasive fMRI.

BACKGROUND: The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). METHODS: Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. RESULTS: The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. CONCLUSION: The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.

Factors that contribute to trait mindfulness level among hospitalized patients with major depressive disorder.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets.

Effect of cognitive behavioral intervention on anxiety, depression, and quality of life in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on quality of life, anxiety, and depression in patients with epilepsy. METHODS: Each study subject was randomly assigned to a CBT (n=46) or control (n=49) group (1:1 ratio), and the first group underwent an 8-week CBT treatment. Anxiety, depression, and quality of life (QOLIE-31) were assessed at both baseline and endpoint using the Self-Rating Anxiety Scale (SAS), Hamilton Depression Scale (HDMA) and quality of life in Epilepsy-31 (QOLIE-31) scales. The statistical analyses included between-and within-group comparisons of the effects of CBT on these measures and associations with demographic and clinical variables. RESULTS: No differences were found between variables at baseline (P>0.05). The repeated-measures analyses found that CBT group had greater improvement in depression score compared to the control group (P<0.05). The analysis of anxiety score showed that compared to the control group, CBT intervention had no statistical significance in the total anxiety population. However, the CBT intervention decreased anxiety in women and Combined-drug group (P<0.05). The CBT group had greater improvement in overall score, medication effect, and seizure worry score than the control group (P<0.05). Stratified analysis found total and medication effects score of CBT intervention group for the combined-drug group were higher than those of the single drug group (P<0.05). CONCLUSION: Increases in overall scores, seizure worry, cognitive functioning, and medication effect were better in the CBT group. CBT can improve anxiety, depression, and quality of life in patients with epilepsy. Women and combined-drug patients with epilepsy benefit most from CBT.

Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson's Disease.

Parkinson's disease (PD) is the most common movement disorder and the second most prevalent neurodegenerative disease after Alzheimer's disease. Despite decades of research, there is still no cure for PD and the complicated intricacies of the pathology are still being worked out. Much of the research on PD has focused on neurons, since the disease is characterized by neurodegeneration. However, neuroglia has become recognized as key players in the health and disease of the central nervous system. This review provides a current perspective on the interactive roles that α-synuclein and neuroglial senescence have in PD. The self-amplifying and cyclical nature of oxidative stress, neuroinflammation, α-synucleinopathy, neuroglial senescence, neuroglial chronic activation and neurodegeneration will be discussed. Finally, the compelling role that senolytics could play as a therapeutic avenue for PD is explored and encouraged.

A tract-based spatial statistics study of white matter integrity in epilepsy.

OBJECTIVE: To explore the changes of cerebral white matter diffusion tensor in epilepsy. METHODS: This study was a retrospective study based on diffusion tensor imaging (DTI). Twenty-six epileptic patients and 42 normal controls matched for sex, age and handedness were enrolled in our research. Based on the method of tract-based spatial statistics (TBSS), we analyzed the changes of each relevant parameter index of DTI in white matter of the brain in all subjects, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). RESULTS: In comparison with the control group, epileptic patients had decreased FA and elevated MD, AD, and RD in the anterior thalamic radiation, corticospinal tract, forceps major, forceps minor, cingulum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus and uncinate fasciculus (P < 0.05). CONCLUSION: Widespread white matter integrity was observed in epileptic patients, which may be the structural basis for the development of affective disorders, impaired cognition, and motor abnormalities.

Baseline beliefs about medication are associated with outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance.

The aim of the present study was to explore the effect of baseline beliefs about medication on therapeutic outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance. Ninety-seven inpatients with first-diagnosed depression were included to collect their baseline demographic data to evaluate the Hamilton depression rating scale (HAMD) scores and the beliefs about medicine questionnaire-specific (BMQ-S) scores at baseline and the end of the eight-week treatment. Additionally, we explored the relationship between inpatients' medication beliefs and therapeutic effect of antidepressants. The inpatients were divided into remitted depression and unremitted depression groups according to outcomes at the end of the eight-week treatment. There was no significant difference in the baseline HAMD between the two groups (P > 0.050). The scores on the BMQ-S of the unremitted group were significantly lower than those of the remitted group (P < 0.001). The HAMD scores were significantly reduced in both groups after the eight-week treatment (P < 0.001). There was no significant difference in the BMQ-S scores before and after the treatment (P > 0.050). The medication beliefs of the unremitted inpatients after the treatment were still lower than those of the remitted inpatients (P < 0.001). Logistic-regression analysis showed that low BMQ-S scores at the baseline were an independent risk factor for antidepressant efficacy. Beliefs about medication at baseline may be correlated with the therapeutic efficacy in inpatients with first-diagnosed depression under supervised therapeutic compliance.

Clinical characteristics of the first known cases of death caused by COVID-19 pneumonia.

Severe pneumonia caused by COVID-19 has resulted in many deaths worldwide. Here, we analyzed the clinical characteristics of the first 17 reported cases of death due to COVID-19 pneumonia in Wuhan, China. Demographics, initial symptoms, complications, chest computerized tomography (CT) images, treatments, and prognoses were collected and analyzed from the National Health Committee of China data. The first 17 reported deaths from COVID-19 were predominately in older men; 82.35% of patients were older than 65 years, and 76.47% were males. The most common initial symptoms were fever or fatigue (14 cases, 82.35%), respiratory symptoms, such as cough (12 cases, 70.59%), and neurological symptoms, such as headache (3 cases, 17.65%). The most common finding of chest CT was viral pneumonia (5 cases, 29.41%). Anti-infectives (11 cases, 64.71%) and mechanical ventilation (9 cases, 52.94%) were commonly used for treatment. Most of the patients (16 cases, 94.12%) died of acute respiratory distress syndrome (ARDS). Our findings show that advanced age and male gender are effective predictors of COVID-19 mortality, and suggest that early interventions to reduce the incidence of ARDS may improve prognosis of COVID-19 pneumonia patients.

Triiodothyronine levels were positively correlated with opening of collateral circulation in cerebral infarction patients with large artery atherosclerosis.

INTRODUCTION: Non-thyroidal illness syndrome (NTIS) is one of the signs for poor prognosis of cerebral infarction (CI), but its risk factors had never been explored. In this study, we analyzed the potential effect of collateral circulation on prognosis prediction of triiodothyronine for large artery atherosclerosis cerebral infarction (LAA-CI) patients. MATERIAL AND METHODS: Clinical data of CI patients between 2012 and 2014 were collected. Imaging inspection was used for determining TOAST classification and evaluating collateral circulation. One-year follow-up was conducted for mRS score by telephone. RESULTS: T3 level in the NTIS group (p = 0.001) was significantly decreased while TSH level (p < 0.001) was increased. Patients in the NTIS group had a poorer prognosis (p = 0.008) and the main reason was the high mortality (p = 0.002). NTIS predicted poor collateral circulation (p = 0.026) and good collateral circulation tended to be less likely concomitant with NTIS (p = 0.001). Logistic regression analysis showed that triiodothyronine concentrations (OR = 4.760, 95% CI: 1.981-11.456, p < 0.001) were positively correlated with but advanced age (OR = 0.756, 95% CI: 0.645-0.886, p = 0.001) negatively with opening of collateral circulation. CONCLUSIONS: Poor opening of collateral circulation was likely to mediate the prediction of NTIS for prognosis of LAA-CI patients.

Nutrition, Physical Exercise, and the Prevalence of Sarcopenia in Elderly Residents in Nursing Homes in China.

BACKGROUND This study aimed to investigate the factors associated with sarcopenia in elderly residents in three nursing homes in Suzhou City, East China including the association with nutrition and physical exercise. MATERIAL AND METHODS Elderly residents (n=316) from three nursing homes included 112 men and 204 women. The appendicular skeletal muscle index (ASMI), grip strength, and movements were measured to diagnose sarcopenia. The correlation between sarcopenia with age, sex, body mass index (BMI), ASMI, upper arm circumference, calf circumference, muscle content, grip strength, dietary intake, degree and duration of movement were also assessed. RESULTS The prevalence of sarcopenia was 28.8% (30.4% for men and 27.9% for women). Patients with sarcopenia were older compared with controls. Height, BMI, upper arm circumference, calf circumference and arm muscle mass, lower limb muscle mass, limb skeletal muscle index and ASMI, grip strength, and pace of movement were lower than controls. The prevalence of sarcopenia correlated with the intake of meat, fish, eggs, and milk, and duration of weekly aerobic and resistance exercise. Logistic regression analysis showed a positive correlation between the prevalence of sarcopenia and age, and a negative correlation between BMI and consumption of meat, eggs, and milk. CONCLUSIONS The prevalence of sarcopenia in elderly residents in three nursing homes in Suzhou City was 28.8%. Increasing age was a risk factor for sarcopenia. Increased BMI and a diet containing meat, eggs, and milk were protective factors. The findings from this study provide support that adequate dietary protein can prevent sarcopenia in the elderly.

T-lymphocyte subsets as a predictive biomarker for stroke-associated pneumonia.

The aim of this study was to facilitate the clinical treatment and prognosis of stroke-associated pneumonia (SAP) by examining changes in T-lymphocyte subsets. Stroke patients admitted in Suzhou Hospital between 2014 and 2016 participated in the study. Patients were divided into a pneumonia group (50 patients) and a non-pneumonia group (254 patients) based on a diagnosis of pneumonia. Information regarding risk factors for ischemic stroke was collected from all patients using a questionnaire. Compared with non-SAP patients, SAP patients were older, dysphagic, smokers, had higher NIH stroke scale (NIHSS) scores and neutrophil: lymphocyte ratio, had higher leukocyte, neutrophil, and CD8 levels, had lower CD3, CD4, and lymphocyte levels, and had a lower CD4:CD8 ratio. Patients with a higher NIHSS score had higher CD8 levels, lower CD3 and CD4 levels, and a lower CD4:CD8 ratio. No significant differences in T-lymphocyte subsets were found between the left and right cerebral hemispheres. After adjusting for other variables, smoking, dysphagia, NIHSS score, and CD4:CD8 ratio were positively associated with SAP. The areas under the receiver operating characteristic curve for dysphagia, NIHSS score, CD4:CD8 ratio, CD4:CD8 ratio + NIHSS score, and Dysphagia+ CD4:CD8 ratio + NIHSS score were 0.583 (95% CI: 0.490-0.675), 0.791 (95% CI: 0.724-0.859), 0.676 (95% CI: 0.593-0.759), 0.846 (95% CI: 0.790-0.902), and 0.867 (95% CI: 0.815-0.918), respectively. A few T-lymphocyte subsets may increase susceptibility to pneumonia after acute ischemic stroke. Thus, the detection of T-lymphocyte subsets may predict the risk of SAP in such patients.

Influence of renal function on the association between homocysteine level and risk of ischemic stroke.

We examined whether the association between total homocysteine (tHCY) and risk of ischemic stroke (IS) varies depending on renal function to gain insight into why tHCY-lowering vitamins do not reduce the incidence of cardiovascular disease in clinical trials. We analyzed data from 542 IS patients with large artery atherosclerosis (LAA) or small artery occlusion (SAO) after stratification by estimated glomerular filtration rate (eGFR) to evaluate renal function. We found that tHCY level was positively associated with the occurrence of IS in both LAA (OR: 1.159, 95% CI: 1.074-1.252, P<0.001) and SAO (OR: 1.143, 95% CI: 1.064-1.228, P<0.001) patients and in LAA (OR: 1.135, 95% CI: 1.047-1.230, P=0.002) and SAO (OR: 1.159, 95% CI: 1.060-1.268, P=0.001) subgroups with normal renal function but not in LAA or SAO subgroups with renal insufficiency. eGFR level was positively associated with IS in LAA (OR: 1.022, 95% CI: 1.010-1.034, P<0.001) and SAO (OR: 1.024, 1.012-1.037, P<0.001) subgroups with normal renal function but was negatively associated with IS in LAA (OR: 0.875, 95% CI: 0.829-0.925, P<0.001) and SAO (OR: 0.890, 95% CI: 0.850-0.932, P<0.001) subgroups with renal insufficiency. Folic acid level was negatively associated with IS in LAA (OR: 0.734, 95% CI: 0.606-0.889, P=0.002) and SAO (OR: 0.861, 95% CI: 0.767-0.967, P=0.012) subgroups with renal insufficiency. Therefore, renal function as evaluated by eGFR exerts a significant influence on the association between tHCY and risk of IS.

Association between hyperhomocysteinemia and stroke with atherosclerosis and small artery occlusion depends on homocysteine metabolism-related vitamin levels in Chinese patients with normal renal function.

This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.

Low T3 syndrome predicts severe neurological deficits of cerebral infarction inpatients with large artery artherosclerosis in internal carotid artery system.

OBJECTIVES: The low triiodothyronine (T3) syndrome indicates poor prognosis for patients with cerebral infarction. It is unknown, however, whether basic conditions or severities in the patients with the low T3 syndrome are different compared to those without the low T3 syndrome. METHODS: We compared the risk factors and the severity of the disease using the National Institutes of Health stroke scale (NIHSS) score at the worst condition for cerebral infarction in patients with or without the low T3 syndrome in order to better understand the characteristics underlying the worse prognosis in patients with the low T3 syndrome. RESULTS: We found that cerebral infarction patients with the low T3 syndrome were significantly older (p<0.001) and significantly more likely to be female (p=0.002) and had hypertension (p=0.04) or homocystinemia (p=0.001), but less likely to smoke (p=0.008), compared to patients without the low T3 syndrome. The proportion of NIHSS score ≥8 in the patients with LAA-ICA-associated cerebral infarction accompanied by the low T3 syndrome was significantly higher than in those without the low T3 syndrome (p=0.001). CONCLUSION: We concluded that increased numbers of risk factors for cerebral infarction and more severe neurological deficits may be important causes for worse prognosis in the patients with the low T3 syndrome which may more likely occur in patients with LAA-ICA cerebral infarction. Intense secondary prevention in cerebral infarction especially in older women are needed.