Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Predictors for early-onset psychotic symptoms in patients newly diagnosed with Parkinson's disease without psychosis at baseline: A 5-year cohort study.

AIMS: To investigate the risk factors for early-onset psychosis in Parkinson's disease (PD) in a cohort of patients from the Parkinson's Progression Markers Initiative. METHODS: Longitudinal data on motor and non-motor features, dopamine transporter (DAT) imaging, and cerebrospinal fluid (CSF) measurements were collected. The survival probability of psychotic symptoms, potential risk factors for psychosis development over a 5-year follow-up period, and the performance of the prediction model were evaluated. RESULTS: Among the 338 newly diagnosed patients with PD, 83 developed psychotic symptoms. Gastrointestinal autonomic dysfunction, presence of probable rapid-eye-movement sleep behavior disorder, and the ratio Aß42: total-tau could independently predict onset of psychosis in PD (hazard ratio (HR) = 1.157, 95% confidence interval (CI) 1.022-1.309, p = 0.021, HR = 2.596, 95% CI 1.287-5.237, p = 0.008, and HR = 0.842, 95% CI 0.723-0.980, p = 0.027, respectively). The combined model integrating baseline clinical predictors, DAT imaging, and CSF measurements achieved better sensitivity than the clinical predictors alone (area under the curve = 0.770 [95% CI 0.672-0.868] vs. 0.714 [95% CI 0.625-0.802], p = 0.098). CONCLUSION: We identified clinical and CSF predictors of early-onset psychosis in patients with PD. Our study provides evidence and implications for prognostic stratification and therapeutic approaches for PD psychosis.

Correlation of slow-wave sleep with motor and nonmotor progression in Parkinson's disease.

OBJECTIVE: This study aimed to explore the association between slow-wave sleep and the progression of motor and nonmotor symptoms in patients with PD. METHODS: Data were collected from the Parkinson's Progression Markers Initiative study. Slow-wave sleep, also known as deep non-rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated-measures analysis of variance and linear regression. RESULTS: A total of 102 patients with PD were included in the study, with a median follow-up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow-up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (ß = -0.251, p = 0.021; 95% confidence interval = -0.465 to -0.038). INTERPRETATION: The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway.

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

Long-term safety and efficacy of stenting on correcting internal jugular vein and cerebral venous sinus stenosis.

OBJECTIVES: To compare the long-term safety and efficacy of stenting in correcting cerebral venous sinus stenosis (CVSS) and internal jugular venous stenosis (IJVS). METHODS: Patients confirmed with CVSS or IJVS by imaging were enrolled in this real-world study from 2014 through 2021. Clinical characteristics and long-term outcomes of these two diseases entities post-stenting were followed up and compared. RESULTS: Three hundred and nineteen patients were enrolled in this study, with a mean age of 48.83 years and a BMI of 25.08 on average. In which, 144 patients underwent stenting, the stenotic segments were corrected and the venous blood flow was restored immediately post-stenting. At 6.15 ± 1.67 days follow-up, significant improvement was observed in headache, tinnitus, insomnia, ICP, and mean pressure gradient in both groups (all p < 0.05). At 30.53 ± 4.41 months follow-up post-stenting, the headache, tinnitus, visual loss, papilledema, and insomnia were attenuated remarkably or even completely disappeared. The Frisen papilledema grade scores declined from 2 (0-4) to 1 (0-3) in IJVS group and from 4 (1-5) to 1 (0-4) in CVSS group compared to the baseline. One hundred and twenty-seven out of the 144 patients (95.5%) maintained sufficient blood flow verified by followed up computed tomographic venography or contrast-enhanced magnetic resonance angiography. Adverse events related to stenting included three cases of intraluminal restenosis and three cases of in-stent thrombosis, no intracranial hemorrhage, venous thromboembolisms, stent-adjacent stenosis, and stent displacement occurred. INTERPRETATION: Using stents to correct IH and related neurological issues has shown to be a safe and effective approach for both IJVS and CVSS.

The performance of patients with cerebral microbleeds in different cognitive tests: A cross-sectional study.

Background: The clinical features and pathological process of cerebral microbleed (CMB)-related cognitive impairment are hot topics of cerebral small vessel disease (CSVD). However, how to choose a more suitable cognitive assessment battery for CMB patients is still an urgent issue to be solved. This study aimed to analyze the performance of CMB patients on different cognitive tests. Methods: This study was designed as a cross-sectional study. The five main markers of CSVD (including the CMB, white matter hyperintensities, perivascular spaces, lacunes and brain atrophy) were assessed according to magnetic resonance imaging. The burden of CMB was categorized into four grades based on the total number of lesions. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Trail-Making Test (TMT, Part A and Part B), Stroop color-word test (Stroop test, Part A, B and C), Verbal Fluency Test (VF, animal), Digit-Symbol Substitution Test (DSST), Digit Cancellation Test (DCT) and Maze. Multiple linear regression analysis was conducted to analyze the association between CMB and cognitive findings. Results: A total of 563 participants (median age of 69 years) were enrolled in this study, including 218 (38.7%) CMB patients. CMB patients showed worse performance than non-CMB subjects in each cognitive test. Correlation analysis indicated the total number of CMB lesions had positive correlations with the time of TMT, Maze and Stroop test, and negative correlations with the performance of MMSE, VF, DSST, and DCT. After the adjustment for all the potential confounders by linear regression, the CMB burden grade was correlated with the performance of VF, Stroop test C, Maze and DCT. Conclusion: The presence of CMB lesions was associated with much worse cognitive performances. In VF, Stroop test C, Maze and DCT, the correlations between CMB severity and assessment results were more significant. Our study further confirmed that the attention/executive function domain was the most commonly evaluated in CMB, which provided a picture of the most utilized tools to analyze the prognostic and diagnostic value in CMB.

The disruption of white matter integrity of systemic striatal circuits in alcohol-dependent males with physiological cue reactivity.

Alcohol dependence (AD) is a chronic and relapsing disorder. Conditioned cues associated with the rewarding properties of drugs could trigger motivational/physiological reactions and render subjects vulnerable to relapse. Striatal circuit dysfunction has been implicated in alcohol addiction behaviours. However, little is known about the striatal tracts structural connectivity changes underlying cue induced reactivity in AD. In our present study, we recruited 51 patients with AD; 31 individuals had physiological response. We used seed-based classification by probabilistic tractography with nine target masks to explore the white matter integrity of striatal circuits in physiological responders (N = 31), non-responders (N = 20), and healthy controls (N = 27). Compared with healthy controls, physiological responders showed lower fractional anisotropy (FA) and/or higher mean diffusivity in the striatum-dorsolateral prefrontal cortex (dlPFC), striatum-ventral lateral prefrontal cortex, striatum-supplementary motor area (SMA), and striatum-insular. Considering age and smoking are potential nuisances to diffusion parameters, an analysis of covariance also was conducted and similar results were found. We also found the cue-induced physiological response was negatively associated with the FA of the striatum-SMA (r = -0.287; p = 0.045) and left striatum-dlPFC (r = -0.253; p = 0.079) in AD. In our study, we found abnormal integrity of striatal circuit structural connectivity in AD with physiological cue reactivity, especially trajectory from prefrontal cortex and insular. We also found the FA of striatal tracks was negatively associated with the degree of cue reactivity. Our findings provide further evidence for reduced white matter integrity of striatal circuits for cue reactivity in male individuals with AD.

Predictors of cognitive impairment in newly diagnosed Parkinson's disease with normal cognition at baseline: A 5-year cohort study.

Background and objective: Cognitive impairment (CI) is a substantial contributor to the disability associated with Parkinson's disease (PD). We aimed to assess the clinical features and explore the underlying biomarkers as predictors of CI in patients with newly diagnosed PD (NDPD; less than 2 years). Methods: We evaluated the cognitive function status using the Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological tests at baseline and subsequent annual follow-up for 5 years from the Parkinson's Progression Markers Initiative (PPMI) database. We assessed the baseline clinical features, apolipoprotein (APO) E status, ß-glucocerebrosidase (GBA) mutation status, cerebrospinal fluid findings, and dopamine transporter imaging results. Using a diagnosis of CI (combined mild cognitive impairment and dementia) developed during the 5-year follow-up as outcome measures, we assessed the predictive values of baseline clinical variables and biomarkers. We also constructed a predictive model for the diagnosis of CI using logistic regression analysis. Results: A total of 409 patients with NDPD with 5-year follow-up were enrolled, 232 with normal cognitive function at baseline, and 94 patients developed CI during the 5-year follow-up. In multivariate analyses, age, current diagnosis of hypertension, baseline MoCA scores, Movement disorder society Unified PD Rating Scale part III (MDS-UPDRS III) scores, and APOE status were associated with the development of CI. Predictive accuracy of CI using age alone improved by the addition of clinical variables and biomarkers (current diagnosis of hypertension, baseline MoCA scores, and MDS-UPDRS III scores, APOE status; AUC 0.80 [95% CI 0.74-0.86] vs. 0.71 [0.64-0.77], p = 0.008). Cognitive domains that had higher frequencies of impairment were found in verbal memory (12.6 vs. 16.8%) and attention/processing speed (12.7 vs. 16.9%), however, no significant difference in the prevalence of CI at annual follow-up was found during the 5-year follow-up in NDPD patients. Conclusion: In NDPD, the development of CI during the 5-year follow-up can be predicted with good accuracy using a model combining age, current diagnosis of hypertension, baseline MoCA scores, MDS-UPDRS III scores, and APOE status. Our study underscores the need for the earlier identification of CI in NDPD patients in our clinical practice.

A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

SIRT3 Enhances the Protective Role of Propofol in Postoperative Cognitive Dysfunction via Activating Autophagy Mediated by AMPK/mTOR Pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery and anesthesia. In this study, we aimed to determine the neuroprotective mechanism of Sirtuin 3 (SIRT3) and propofol in POCD. METHODS: The cognitive dysfunction models in C57BL/6J mice were induced and treated, then cognitive function of mice were tested using morris water maze and novel object recognition tests. Primary neurons were stimulated by lipopolysaccharide (LPS) to mimic neuroinflammation during POCD. Meanwhile, cells were treated with propofol. 3-methyladenine (3-MA) was administrated to inhibit autophagy in neurons. SIRT3 overexpression vector was constructed to upregulate SIRT3. Biomarker changes in inflammation, oxidative stress and autophagy were determined in vivo and in vitro. RESULTS: Propofol enhanced the spatial cognitive ability and novel objective recognition of POCD mice. Inflammation and oxidative stress were observed in the hippocampus, which were inhibited by propofol treatment. During POCD, SIRT3 expression and autophagy in the hippocampus was decreased; propofol activated autophagy and upregulated SIRT3. In LPS-stimulated neurons, SIRT3 upregulation enhanced the anti-inflammation and anti-oxidative stress roles of propofol; SIRT3 elevated propofol-activated autophagy in neurons undergoing LPS administration. Moreover, 3-MA reversed propofol-induced biomarker changes in inflammation, oxidative stress and autophagy in LPS-stimulated neurons. In POCD mice, SIRT3 upregulation enhanced the cognitive function during propofol treatment; SIRT3 overexpression elevated the inhibitory role of propofol in inflammation, oxidative stress and autophagy. AMPK/mTOR pathway was activated in response to propofol treatment and SIRT3 enhanced the signaling activation. CONCLUSIONS: SIRT3 enhances the protective effect of propofol on POCD by triggering autophagy that eliminates oxidative stress and inhibits the production of pro-inflammatory cytokines.

Temporal Variation in Disease Onset and Clinical Features of Lewy Body Disease in China.

BACKGROUND: Lewy body dementia is the second most common neurodegenerative dementia, but data concerning the onset age and clinical features in the prodromal stage remain limited in China. OBJECTIVE: To investigate the associations between onset age and clinical manifestations of cognitive impairment with Lewy bodies in a large-sample cohort. METHODS: We included 74 patients with mild cognitive impairment with Lewy bodies (MCI-LB), 533 patients with dementia with Lewy bodies (DLB), 118 patients with Parkinson's disease with MCI (PD-MCI), and 313 patients with Parkinson's disease dementia (PDD) in this multicenter cohort from 22 memory clinics of China from 1 January 2018 to 31 March 2022. The onset age, clinical manifestations, and neuropsychological assessments were recorded and analyzed after reviewing the medical records. RESULTS: The average onset age of memory loss was 68.28 (±7.00) years, and parkinsonism happened 2.00 (±1.24) years later for patients with MCI-LB. The average onset age of parkinsonism was 60.56 (±8.96) years, and the memory loss happened 3.49 (±3.02) years later for patients with PD-MCI. Rapid eye movement sleep behavior disorder and visual hallucinations were frequently reported in MCI-LB, DLB, and PDD, while visual hallucinations were least frequently reported in PD-MCI. Lower scores of MMSE and depression, and higher scores of activities of daily living and delusions, were independently associated with older onset age in DLB. CONCLUSION: The onset of PD-MCI precedes MCI-LB, and memory loss occurs 3 years after parkinsonism. The onset age is associated with cognition and neuropsychiatric symptoms in process.

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study.

BACKGROUND: Research on sex ratios of Lewy body dementia is controversial, established in small samples, and rarely focused on prodromal stage. The objective is to investigate the clinical sex ratios (men/women) and their associations with clinical features among individuals with mild cognitive impairment with Lewy bodies (MCI-LB), dementia with Lewy bodies (DLB), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) in China. METHODS: We conducted a multicenter cohort study, including 1038 individuals with probable MCI-LB, DLB, PD-MCI, or PDD diagnosis from 22 memory clinics in China from January 2018 to March 2022, and recorded their demographic and clinical data by reviewing medical records. Descriptive and regression analyses were used to calculate the sex ratio (men/women), and its associations with demographic and clinical data. RESULTS: In this study, men comprised 35.14% (men/women sex ratio = 0.54) for MCI-LB, 46.72% (men/women sex ratio = 0.88) for DLB, 63.56% (men/women sex ratio = 1.74) for PD-MCI, and 52.40% (men/women sex ratio = 1.10) for PDD. Sex ratios roughly increased with age. Men had more parkinsonism (p = 0.000) and less fluctuating cognition (p = 0.024) in MCI-LB, and those with PD-MCI had more RBD (p = 0.001). Women with PD-MCI had lower MMSE scores (ß ± standard error = - 1.24 ± 0.58, p = 0.04), more irritability (0.95 ± 0.46, p = 0.04) and fluctuating cognition (- 3.41 ± 1.31, p = 0.01), and less parkinsonism (- 2.10 ± 0.97, p = 0.03) than men after adjusting for demographic and cardiometabolic conditions. CONCLUSION: There were more women in DLB and MCI-LB, and more men in PD-MCI and PDD. The sex distribution, demographic, and clinical characteristics differed, which strengthened the independence and heterogeneity of the four diseases, and indicated sex-sensitive strategies for management of dementia necessary.

Impulsive trait mediates the relationship between white matter integrity of prefrontal-striatal circuits and the severity of dependence in alcoholism.

Background: Alcohol dependence (AD) remains one of the major public health concerns. Impulsivity plays a central role in the transfer from recreational alcohol use to dependence and relapse. White matter dysfunction has been implicated in alcohol addiction behaviors and impulsivity. However, little is known about the role of systematic striatal structural connections underlying the mechanism of impulsive traits in AD. Methods: In our study, we used seed-based classification by probabilistic tractography with five target masks of striatal circuits to explore the differences in white matter integrity (fractional anisotropy, FA) in AD male patients (N = 51) and healthy controls (N = 27). We mainly explored the correlation between FA of the striatal circuits and impulsive traits (Barratt Impulsiveness Scale, BIS-11), and the mediation role of impulsivity in white matter integrity and the severity of alcohol dependence. Results: Compared with healthy controls, AD showed much lower FA in the left and right striatum-supplementary motor area (SMA) and left striatum-amygdala. We also found the decreased FA of right striatum-vlPFC was correlated with higher impulsivity. Besides, the relationship between reduced FA of right striatum-vlPFC and severity of dependence could be mediated by impulsivity. Conclusion: In our study, we found disrupted white matter integrity in systematic striatal circuits in AD and the decreased FA of right striatum-vlPFC was correlated with higher impulsivity in AD. Our main findings provide evidence for reduced white matter integrity of systematic striatal circuits and the underlying mechanisms of impulsivity in male AD individuals.

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). FINDING: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. INTERPRETATION: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. FUNDING: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

Correlation between Bispectral Index and Prognosis of Patients with Acute Cerebral Infarction.

INTRODUCTION: This study aimed to investigate the clinical value of bispectral index (BIS) monitoring in assessing the consciousness and prognosis of Acute Cerebral Infarction (ACI) patients. METHODS: In total, 64 patients who suffered from ACI with consciousness disturbance were enrolled in this study. Glasgow Coma Scale (GCS) was performed to evaluate the consciousness level of ACI patients, and BIS was used to monitor the depth of anesthesia and sedation. Then, patients were divided into good prognosis, poor prognosis and death groups according to Modified Rankin Score (mRS). Discrimination analysis of BIS values and GCS score for the prediction of prognosis was performed using the Receiver Operator Characteristic (ROC) curve. RESULTS: GCS score and BIS values showed statistically significant differences among the three groups. Spearman rank correlation analysis revealed a significant positive correlation between BIS values and GCS score, while BIS values was negatively related with mRS. The ROC curve of prognosis prediction showed strong prognostic power, with Area Under the Curves (AUCs) between 0.830 and 0.917. Moreover, the AUC of BISmean score was higher than that of BISmax, BISmin and GCS, and BISmean of 74 was the best cut-off point for good prognosis. CONCLUSION: BIS directly reflects the degree of consciousness disturbance in ACI patients, and thus accurately predicts the prognosis, indicating potential application values of BIS in clinical practice.

Higher Total Cerebral Small Vessel Disease Burden Was Associated With Mild Cognitive Impairment and Overall Cognitive Dysfunction: A Propensity Score-Matched Case-Control Study.

BACKGROUND AND OBJECTIVE: The combination of neuroimaging and cognition characteristics may provide complementary information for early identification of mild cognitive impairment (MCI). This study aimed to establish the clinical relevance between cerebral small vessel disease (CSVD) burden and MCI and further explored the cognitive characteristics linked to CSVD applying a propensity score matching (PSM) approach. METHODS: The study was designed as a case-control study. All the subjects underwent the standard clinical assessments, neuropsychological testing battery (including global cognition, memory, executive function, and speed and motor control domains), and brain magnetic resonance imaging (MRI). A 1:2 nearest-neighbor matching approach without replacement was employed with a caliper of 0.15 in the PSM approach. RESULTS: A total of 84 MCI patients and 186 cognitively normal controls were included in this study. After PSM, 74 MCI patients and 129 controls were successfully matched, and the covariate imbalance was well eliminated. Compared with controls, the MCI group had more severe CSVD burden. In the binary logistic regression analysis, CSVD was associated with MCI after adjusting for all confounders. The results of multivariate linear regression analyses showed that higher total MRI CSVD burden was related to the deficit of cognitive performance in global cognition and three important cognitive domains after adjusting for all confounders. CONCLUSION: Cerebral small vessel disease was an independent risk factor of MCI. Moreover, higher total MRI CSVD burden was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults.

Clinical characteristics of Lewy body dementia in Chinese memory clinics.

BACKGROUND: Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics. METHODS: A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance. RESULTS: The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9-5.9%) and 7.3% (6.7-8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p<0.001), the CDR (1.8 ± 0.7 vs. 1.6 ± 0.7, p = 0.002), and the MTA (1.8 ± 0.7 vs. 1.2 ± 0.6, p = 0.002). Diagnostic differences for LBD exist among the centers; their reported proportions of those with DLB ranged from 0.7 to 11.4 and those with PDD ranged from 0.0 to 2.9%. CONCLUSIONS: Variations of diagnoses exists in different regions and the clinical proportion of LBD is likely to be underestimated in China and other regions.

Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases.

Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. It has been noted that glial cells including astrocytes (which outnumber other cell types in the CNS) essentially contribute more to the BBB integrity, extracellular homeostasis, neurotransmitter release, regulation of neurogenic niches in response to neuroinflammatory stimulus, and synaptic plasticity. In a recent study for NDDs utilizing cellular and molecular biology and genetic and pharmacological tools, the role of reactive astrocytes (RACs) and gliosis was demonstrated, able to trigger pathophysiological/psychopathological detrimental changes during the disease progression. We speculate, in particular, the BBB, the NVU, and changes of the astrocytes (potentially different populations from the RACs) not only interfere with neuronal development and synaptogenesis, but also generate oxidative damages, contribute to beta-amyloid clearances and disrupted vasculature, as well as lead to neuroinflammatory disorders. During the past several decades, stem cell therapy has been investigated with a research focus to target related neuro-/vascular pathologies (cell replacement and repair) and neurological/psychiatric symptoms (paracrine protection and homeostasis). Evidence shows that transplantation of neurogenic or vasculogenic cells could be achieved to pursue differentiation and maturation within the diseased brains as expected. It would be hoped that, via regulating functions of astrocytes, astrocytic involvement, and modulation of the BBB, the NVU and astrocytes should be among major targets for therapeutics against NDDs pathogenesis by drug and cell-based therapies. The non-invasive strategies in combination with stem cell transplantation such as the well-tested intranasal deliveries for drug and stem cells by our and many other groups show great translational potentials in NDDs. Neuroimaging and clinically relevant analyzing tools need to be evaluated in various NDDs brains.