Impact of Increased Hemoglobin on Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Studies of the impact of increased hemoglobin on spontaneous intracerebral hemorrhage (ICH) are limited. The present study aimed to explore the effect of increased hemoglobin on ICH. METHODS: A retrospective single-center study using medical records from a database processed by univariate and multivariate analyses was performed in the People's Hospital of Tibet Autonomous Region in Lhasa, Tibet, China. RESULTS: The mean hemoglobin level in 211 patients with ICH was 165.03 ± 34.12 g/l, and a median hematoma volume was 18.5 ml. Eighty-eight (41.7%) patients had large hematomas (supratentorial hematoma ≥ 30 ml; infratentorial hematoma ≥ 10 ml). No differences in ICH risk factors between the groups with different hemoglobin levels were detected. Increased hemoglobin was independently associated with large hematomas [odds ratio (OR) 1.013, P = 0.023]. Increased hemoglobin was independently associated with ICH with subarachnoid hemorrhage (OR 1.014, P = 0.016), which was more pronounced in men (OR 1.027, P = 0.002). Increased hemoglobin was independently associated with basal ganglia hemorrhage and lobar hemorrhage in men (OR 0.986, P = 0.022; OR 1.013, P = 0.044, respectively) but not in women (P > 0.1). CONCLUSIONS: Increased hemoglobin was independently associated with large hemorrhage volume. Increased hemoglobin was independently associated with lobar hemorrhage in men and ICH with subarachnoid hemorrhage, which was more pronounced in men. Additional studies are needed to confirm our findings and explore potential mechanisms.

Prevalence and Risk Factors of White Matter Lesions in Tibetan Patients Without Acute Stroke.

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People's Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.

Characteristics of acute ischemic stroke in hospitalized patients in Tibet: a retrospective comparative study.

BACKGROUND: Numerous studies on acute ischemic stroke (AIS) have been conducted at low-altitude regions, and the related findings have been used to guide clinical management. However, corresponding studies at high altitude are few. This study aimed to analyse the clinical characteristics of AIS patients at high-altitude regions through a hospital-based comparative study between Tibet and Beijing. METHODS: This study included the diagnoses of AIS patients from People's Hospital of Tibet Autonomous Region (PHOTAR) and Peking University First Hospital (PUFH) between 1 January 2014 and 31 December 2017, where data including patient demographics, treatment time, onset season, risk factors, infarction location, laboratory data, image examination results, treatments, and AIS subtype were collected and compared. Continuous and categorical variables were analysed with a two-sample t-test or Wilcoxon rank sum test and chi-square test, respectively. Significant risk factors were examined with binary logistic regression analysis. RESULTS: In total, 236 and 1021 inpatients from PHOTAR and PUFH were included, respectively. The PHOTAR patients were younger than the PUFH patients (P < 0.001). Young adult stroke, erythrocytosis, and hyperhomocysteinemia were more frequent in PHOTAR patients (all P < 0.001). Other vascular risk factors, including hypertension, diabetes mellitus, hyperlipidaemia, smoking and alcohol consumption history, were less prevalent in PHOTAR patients than in PUFH patients. The rate of intravenous thrombolysis and the rate of within intravenous thrombolysis window time were also lower in PHOTAR patients (both P < 0.001). The PHOTAR group also tended to have anterior circulation infarction. Erythrocytosis and hyperhomocysteinemia were independent risk factors in PHOTAR, and young adults accounted for a larger proportion of stroke cases. CONCLUSION: In Tibet, AIS patients were relatively younger, and anterior circulation infarctions were more common. Erythrocytosis and hyperhomocysteinemia may contribute to these differences. Here, young adult stroke also accounted for a higher proportion, and this may be associated with erythrocytosis. Our findings present the first hospital-based comparative study in Tibet and may contribute to policies for stroke prevention in this region.

The role of carotid stenosis ultrasound scale in the prediction of ischemic stroke.

INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

Nicotinic α4ß2 Cholinergic Receptor Influences on Dorsolateral Prefrontal Cortical Neuronal Firing during a Working Memory Task.

The primate dorsolateral prefrontal cortex (dlPFC) subserves top-down regulation of attention and working memory abilities. Depletion studies show that the neuromodulator acetylcholine (ACh) is essential to dlPFC working memory functions, but the receptor and cellular bases for cholinergic actions are just beginning to be understood. The current study found that nicotinic receptors comprised of α4 and ß2 subunits (α4ß2-nAChR) enhance the task-related firing of delay and fixation cells in the dlPFC of monkeys performing a working memory task. Iontophoresis of α4ß2-nAChR agonists increased the neuronal firing and enhanced the spatial tuning of delay cells, neurons that represent visual space in the absence of sensory stimulation. These enhancing effects were reversed by coapplication of a α4ß2-nAChR antagonist, consistent with actions at α4ß2-nAChR. Delay cell firing was reduced when distractors were presented during the delay epoch, whereas stimulation of α4ß2-nAChR protected delay cells from these deleterious effects. Iontophoresis of α4ß2-nAChR agonists also enhanced the firing of fixation cells, neurons that increase firing when the monkey initiates a trial, and maintain firing until the trial is completed. These neurons are thought to contribute to sustained attention and top-down motor control and have never before been the subject of pharmacological inquiry. These findings begin to build a picture of the cellular actions underlying the beneficial effects of ACh on attention and working memory. The data may also help to explain why genetic insults to α4 subunits are associated with working memory and attentional deficits and why α4ß2-nAChR agonists may have therapeutic potential.SIGNIFICANCE STATEMENT The acetylcholine (ACh) arousal system in the brain is needed for robust attention and working memory functions, but the receptor and cellular bases for its beneficial effects are poorly understood in the newly evolved primate brain. The current study found that ACh stimulation of nicotinic receptors comprised of α4 and ß2 subunits (α4ß2-nAChR) enhanced the firing of neurons in the primate prefrontal cortex that subserve top-down attentional control and working memory. α4ß2-nAChR stimulation also protected neuronal responding from the detrimental effects of distracters presented during the delay epoch, when information is held in working memory. These results illuminate how ACh strengthens higher cognition and help to explain why genetic insults to the α4 subunit weaken cognitive and attentional abilities.

Effects of Blood Pressure in the Early Phase of Ischemic Stroke and Stroke Subtype on Poststroke Cognitive Impairment.

BACKGROUND AND PURPOSE: Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. METHODS: Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). RESULTS: After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). CONCLUSIONS: Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.

Anti-ganglioside antibodies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients.

INTRODUCTION: In this study we investigated the relationships between anti-ganglioside antibodies and Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. RESULTS: In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. CONCLUSIONS: These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470-475, 2017.

Reliability and validity of the international dementia alliance schedule for the assessment and staging of care in China.

BACKGROUND: Clinical and social services both are important for dementia care. The International Dementia Alliance (IDEAL) Schedule for the Assessment and Staging of Care was developed to guide clinical and social care for dementia. Our study aimed to assess the validity and reliability of the IDEAL schedule in China. METHODS: Two hundred eighty-two dementia patients and their caregivers were recruited from 15 hospitals in China. Each patient-caregiver dyad was assessed with the IDEAL schedule by a rater and an observer simultaneously. The Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), and Caregiver Burden Inventory (CBI) were assessed for criterion validity. IDEAL repeated assessment was conducted 7-10 days after the initial interview for 62 dyads. RESULTS: Two hundred seventy-seven patient-caregiver dyads completed the IDEAL assessment. Inter-rater reliability for the total score of the IDEAL schedule was 0.93 (95%CI = 0.92-0.95). The inter-class coefficient for the total score of IDEAL was 0.95 for the interviewers and 0.93 for the silent raters. The IDEAL total score correlated with the global CDR score (ρ = 0.72, p < 0.001), the CDR-sum of box (CDR-SOB, ρ = 0.74, p < 0.001), the total score of MMSE (ρ = -0.65, p < 0.001) and CBI (ρ = 0.70, p < 0.001). All item scores of the IDEAL schedule were associated with the CDR-SOB (ρ = 0.17 ~ 0.79, all p < 0.05). CONCLUSION: The IDEAL schedule is a valid and reliable tool for the staging of care for dementia in the Chinese population.

Report of cold agglutinins in a patient with acute ischemic stroke.

BACKGROUND: Studies on the role of cold agglutinins in the pathogenesis of acute ischemic stroke are scarce. We present a case of an elderly man with acute cerebral infarction probably due to cold agglutinin disease. CASE PRESENTATION: On a cold morning, a 71-year-old male of Han nationality with a complaint of sudden onset left-sided weakness and difficulty in speaking was brought to the emergency department. Diffusion weighted magnetic resonance imaging of the brain showed a high-intensity area in the right basal ganglia and corona radiata. Laboratory test showed the presence of high titers of cold agglutinins. There was no history of common risk factors of atherosclerosis, such as hypertension, diabetes mellitus, coronary artery disease or smoking. After being exposed to warm temperature, and with corticosteroid therapy and blood transfusion, the patient's symptoms relieved rapidly. CONCLUSION: We report here the first case of cerebral infarction probably due to the cold agglutinin disease. The underlying mechanism of cold agglutinins in the pathogenesis of acute ischemic stroke needs to be investigated further.

Tracking mitochondrial Cu(I) fluctuations through a ratiometric fluorescent probe in AD model cells: Towards understanding how AßOs induce mitochondrial Cu(I) dyshomeostasis.

Mitochondrial copper signaling pathway plays a role in Alzheimer's disease (AD), especially in relevant Amyloid-ß oligomers (AßOs) neurotoxicity and mitochondrial dysfunction. Clarifying the relationship between mitochondrial copper homeostasis and both of mitochondrial dysfunction and AßOs neurotoxicity is important for understanding AD pathogenesis. Herein, we designed and synthesized a ratiometric fluorescent probe CHC-NS4 for Cu(I). CHC-NS4 possesses excellent ratiometric response, high selectivity to Cu(I) and specific ability to target mitochondria. Under mitochondrial dysfunction induced by oligomycin, mitochondrial Cu(I) levels gradually increased, which may be related to inhibition of ATP7A-mediated Cu(I) exportation and/or high expression of COX. On this basis, CHC-NS4 was further utilized to visualize the fluctuations of mitochondrial Cu(I) levels during progression of AD model cells induced by AßOs. It was found that mitochondrial Cu(I) levels were gradually elevated during the AD progression, which depended on not only AßOs concentration but also incubation time. Moreover, endocytosis maybe served as a prime pathway mode for mitochondrial Cu(I) dyshomeostasis induced by AßOs during AD progression. These results have provided a novel inspiration into mitochondrial copper biology in AD pathogenesis.

Sleep Characteristics in Older Adults with Different Levels of Risk for Dementia: A Cross-sectional Study.

BACKGROUND: Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive. AIM: The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). METHODS: This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates. RESULTS: Around half of the participants (45.9%) reported poor sleep quality (PSQI＜7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p＜0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p＜0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p＜0.05). CONCLUSION: Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorerself-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

Mental states in caregivers toward people with Alzheimer's disease at different stages.

Introduction: Caring for people with Alzheimer's disease (AD) is burdensome, especially when family members act as caregivers. This multicenter survey first aimed to investigate caregivers' mental states as well as its influencing factors in caring for people with different severities of AD in China. Methods: People with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for caregivers' mental states and living conditions, as well as caregivers' attitudes toward treatment and caring. Logistic regression was used to explore the factors that influence the positive and negative states of caregivers who care for people with different stages of AD. Results: A total of 1,966 valid questionnaires were analyzed (mild AD: 795, moderate AD: 521, severe AD: 650). A total of 73.6% of caregivers maintained normal states (mild group: 71.9%, moderate group: 73.9%, severe group: 75.2%; X2 = 2.023, p = 0.364), and the proportions of caregivers with positive and negative states were 26.3% (mild group: 38.4%, moderate group: 24.6%, severe group: 13.1%; X2 = 119.000, p < 0.001) and 36.5% (mild group: 25.2%, moderate group: 36.9%, severe group: 50.2%; X2 = 96.417, p < 0.001), respectively. The major factors that both influenced caregivers' positive and negative states were the severity of AD, perceived efficacy of treatment, safety issues after AD dementia diagnosis and perceived social support (p < 0.005), while neuropsychiatric symptoms causing stress in caregivers (p < 0.001) only affected the negative states of caregivers. The results of further analysis according to disease severity showed that safety issues after AD dementia diagnosis (p < 0.005) only made significant differences in the mild-to-moderate group. Conclusion: To reduce negative states and promote positive states among caregivers, flexible and sensitive caregiving support could be built on caregivers' demands in caring for people with different stages of AD. The support of emotion, social functioning and nursing skills is one of the significant ways for health workers to enhance caregivers' competency.

Effect of weekend versus weekday admission on the mortality of acute ischemic stroke patients in China: an analysis of data from the Chinese acute ischemic stroke treatment outcome registry.

Background: Due to disparities in medical resources in rural and urban areas as well as in different geographic regions in China, the effect of weekend versus weekday admission on the outcomes of acute ischemic stroke (AIS) patients is unknown. Our aim was to investigate whether the outcomes of AIS patients differ according to the day of admission in China. Methods: The data were extracted from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study database of patients diagnosed with AIS. The chi-square test (χ2) and logistic regression were used to assess mortality for weekday and weekend admissions among AIS patients stratified by rural or urban status and geographic region (including the eastern, northeastern, central, and western regions). Results: In total, 9,256 patients were included in this study. Of these patients, 57.2% were classified as urban, and 42.8% were classified as rural. A total of 6,760 (73%) patients were admitted on weekdays, and 2,496 (27%) were admitted on weekends. There was no significant difference in the mortality rate among patients admitted on weekends compared with those admitted on weekdays in urban (7.5% versus 7.4%) or rural areas (8.8% versus 8.1%; p > 0.05). The mortality rate was the highest among patients admitted on weekends and weekdays (11.6% versus 10.3%) in the northeastern area, without statistical significance before and after adjusting for the patients' background characteristics (p > 0.05). In addition, regression analysis revealed that the mortality of patients admitted on weekdays was more likely to be influenced by regional subgroup, hospital level and intravenous thrombolysis than that of patients admitted on weekends. Conclusion: The weekend effect was not observed in the mortality of patients with AIS regardless of rural-urban status or geographic region in China.

The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients.

OBJECTIVES: The characteristic of nonmotor symptoms in patients with multiple system atrophy (MSA) has varied among previous studies. The objective was to investigatethe nonmotor characteristics in MSA patients with different phenotypes, sex and different onset patterns. METHODS: We performed a retrospective review of 1492 MSA patients. All cases were evaluatedby neurologists and assessed with motormanifestations, nonmotor symptoms, auxiliary examinationand brain MRI scans. RESULTS: Multiple system atrophy-cerebellar ataxia (MSA-C) was the predominant phenotype in 998 patients. Average age of onset (56.8 ± 9.2 years) was earlier, the disease duration (2.4 ± 2.2 year) was shorter and brain MRI abnormalities (49.2 %) were more frequently in MSA-C (P < 0.001). Multiple system atrophy-parkinsonism (MSA-P) patients were more likely to have nonmotor symptoms. After adjusted significant parameters, urinary dysfunction (OR 1.441, 95 %CI = 1.067-1.946, P = 0.017), constipation (OR 1.482, 95 %CI = 1.113-1.973, P = 0.007), cognitive impairment (OR 1.509, 95 %CI = 1.074-2.121, P = 0.018) and drooling (OR 2.095, 95 %CI = 1.248-3.518, P = 0.005) were associated with the MSA-P phenotype. Males were more likely to have orthostatic hypotension, urinary dysfunction, sexual dysfunction, drooling and females in constipation and probable RBD. In different onset patterns, constipation (59.2 %) and probable RBD (28.4 %) were more frequently in autonomiconset pattern. CONCLUSIONS: MSA-C is the predominant phenotype in Chinese patients, while many nonmotor symptoms are more common in MSA-P phenotype. Patients with different sex and onset patterns have different nonmotor characteristics. The different clinical features identified could help the physician counseling of MSA patients more easily and more accurately.

[An analysis of stroke subtypes and influencing factors in different regions of China].

OBJECTIVE: To analyze the stroke subtypes and influencing factors in four largest economic regions of China. METHODS: We analyzed the investigation data of QUEST (Quality Evaluation of Stroke Care and Treatment) study conducted in 2006 which included 62 hospitals in a national scale. According to the concept of four economic regions designed by the Development Research Center of the State Council, we performed the univariate and multivariate analysis for the stroke subtypes and its related risk factors in the different economic regions. RESULTS: There were 3362 (73.5%) ischemic stroke patients and 1214 (26.5%) hemorrhagic stroke patients among the total 4576 first-ever stroke patients. Comparison of stroke subtypes in the four different economic regions was statistically significant (P < 0.001), with a percentage of 80.8% ischemic stroke patients in the northeastern region, 78.9% in the eastern region, 68.3% in the central region and 67.0% in the western region. The comparisons of risk factors such as history of hypertension, diabetes, hyperlipidaemia, coronary artery event, atrial fibrillation, and overweight in the four different economic regions were also statistically significant (P < 0.05). CONCLUSIONS: The subtypes of first-ever stroke vary in the four largest economic regions with a highest proportion of ischemic stroke in the northeastern region and relatively high proportion of hemorrhagic stroke in the central and western economic regions. There are also discrepancies of stroke risk factors in the different economic regions.

Erythrocyte-derived extracellular vesicles aggravate inflammation by promoting the proinflammatory macrophage phenotype through TLR4-MyD88-NF-κB-MAPK pathway.

Transfusion of stored erythrocytes is associated with the increased risk of morbidity and mortality in critical infections, but the mechanism is incompletely understood. Previous studies have suggested that RBC-derived extracellular vesicles (EVs) may be potential risk factors for the occurrence of transfusion-related immunomodulation. The purpose of our study was to evaluate the effects of RBC-derived EVs under inflammatory conditions and explore the underlying mechanisms. In vivo, the activity of EVs was evaluated in cecal ligation and puncture (CLP)-induced sepsis. Our results showed that EVs significantly aggravated the inflammatory response to sepsis in serum and lung tissue by promoting the production of the proinflammatory factors tumor necrosis factor-α (TNF-α）-interleukin-6(IL-6), and interleukin-1ß (IL-1ß) and reduced the survival rate of septic mice in vivo. Importantly, adoptive transfer of EVs-pretreated bone marrow-derived macrophages (BMDMs) obviously aggravated systemic proinflammatory factors in mice after CLP surgery. In vitro, the proinflammatory properties of EVs were shown to elevate TNF-α, IL-6, and IL-1ß levels in lipopolysaccharide (LPS)-stimulated BMDMs. Moreover, EVs promoted LPS-induced macrophage polarization into a proinflammatory phenotype. The underlying mechanism might involve EV-mediated up-regulation of TLR4-MyD88-NF-κB-MAPK activity to favor macrophage cytokine production.

Physical Activity and its Influencing Factors in Community-Dwelling Older Adults With Dementia: A Path Analysis.

Dementia is prevalent in worldwide, and increases the care burden and potential costs. Physical activity (PA) has been increasingly shown to be beneficial for them. This was a cross-sectional observational study aiming to investigate the status of PA among community-dwelling older adults with dementia in Beijing or Hangzhou, China, and verify the relationships between neuropsychiatric symptoms, activities of daily living (ADL), caregivers' fear of patients' falling and their PA using a path analysis approach. The level of PA among 216 included people with dementia was low. PA was related to the neuropsychiatric symptoms, with ADL and caregivers' fear of patients' falling have mediation roles. The findings indicated that person-centered strategies related to the management of these symptoms might be helpful to improve ADL, relieve caregivers' concerns about them falling and consequently foster positive participation in PA.

Cerebrospinal Fluid sTREM2 Has Paradoxical Association with Brain Structural Damage Rate in Early- and Late-Stage Alzheimer's Disease.

BACKGROUND: Recently it has been proposed that microglial response has a stage-dependent effect on the progression of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) sTREM2 has emerged as a promising microglial activation marker. OBJECTIVE: To test the stage-dependent role of microglia by studying the association between baseline sTREM2 and dynamic brain structural changes in AD and mild cognitive impairment (MCI) patients. METHODS: 22 amyloid-ß-positive (A+) and tau-positive (T+) AD and 24 A+T+MCI patients were identified from the Alzheimer's Disease Neuroimaging Initiative. The patients had baseline CSF amyloid-ß, phosphorylated-tau, and sTREM2, and were followed up for at least one year by T1-weighted and diffusion tensor imaging scans. Gray matter volumes and white matter microstructural integrity were evaluated. Linear mixed models were applied to analyze how baseline sTREM2 may influence the rate of brain structural changes while adjusting for the effects of age, APOE4 status, and the CSF core markers. RESULTS: In A+T+AD patients, baseline CSF sTREM2 was associated with faster mean diffusivity increase in the bilateral posterior corona radiata and right superior longitudinal fasciculus. In A+T+MCI patients, baseline CSF sTREM2 was associated slower gray matter volumetric loss in parahippocampal gyrus, left fusiform cortex, left middle temporal gyrus, and left lateral occipital cortex. Baseline CSF sTREM2 also had a protective effect against mean diffusivity increase in right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, left forceps minor, and left uncinate fasciculus. CONCLUSION: Microglial activation at early stage might have a protective effect against neurodegeneration, while at late stage it might facilitate AD. Future efforts on modulating microglial activation could be promising, given a carefully selected time window for intervention.

Mediation of the APOE Associations With Cognition Through Cerebral Blood Flow: The CIBL Study.

Background: The ε4 allele of the apolipoprotein E (APOE) gene is a strong genetic risk factor for aging-related cognitive decline. However, the causal connection between ε4 alleles and cognition is not well understood. The objective of this study was to identify the roles of cerebral blood flow (CBF) in cognitive-related brain areas in mediating the associations of APOE with cognition. Methods: The multiple linear regression analyses were conducted on 369 subjects (mean age of 68.8 years; 62.9% of women; 29.3% of APOE ε4 allele carriers). Causal mediation analyses with 5,000 bootstrapped iterations were conducted to explore the mediation effects. Result: APOE ε4 allele was negatively associated with cognition (P < 0.05) and CBF in the amygdala, hippocampus, middle temporal gyrus, posterior cingulate, and precuneus (all P < 0.05). The effect of the APOE genotype on cognition was partly mediated by the above CBF (all P < 0.05). Conclusion: CBF partially mediates the potential links between APOE genotype and cognition. Overall, the APOE ε4 allele may lead to a dysregulation of the vascular structure and function with reduced cerebral perfusion, which in turn leads to cognitive impairment.