Effect of Carotid Artery Stenting and Extracranial-Intracranial By-Pass on Cognitive Function: Preliminary Results

Background: To compare the neuropsychological consequences after carotid artery stenting (CAS) and extracranial-intracranial by-pass (EC-IC by-pass). Methods: A total of 43 patients referred to CAS, 32 patients referred to EC-IC by-pass and 43 control subjects were enrolled in the study. Neuropsychologic testing was performed before and three months after procedure. A paired Student t test was used to compare neuropsychologic test scores at baseline and three months after procedure in each group. Cognitive changes in a three-month follow-up were not normally distributed and compared among/between groups with Kruskal-Wallis test. Results: Three months after the treatment both the CAS and EC-IC by-pass groups showed improved cognitive performance compared to baseline, whereas the same improvement wasn’t seen in the control group. The scores from Activities of Daily Living also improved in all three groups in a three-month follow-up, and EC-IC group presented a more distinct increase in daily life abilities comparing to the other two groups. Conclusions: CAS and EC-IC by-pass in patients with a carotid or intracranial stenosis may result in cognitive improvement three months after surgery.

Reproducible Abnormalities and Diagnostic Generalizability of White Matter in Alzheimer’s Disease

Alzheimer’s disease(AD)is associated with the impairment of white matter(WM)tracts.The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets[321 patients with AD,265 patients with mild cognitive impairment(MCI),279 normal controls(NC)],a unified pipeline,and independent site cross-validation.Automated fiber quantification was used to extract diffusion profiles along tracts.Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC.Machine learning models using tract-based features showed good generalizability among independent site cross-validation.The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups.We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.

阿尔茨海默病多中心独立的、可重复的海马影像组学标志物:早期识别、纵向进展和生物学基础

脑内海马结构的形态学变化是阿尔茨海默病(AD)的影像学标记之一.海马的影像组学特征是否可以作为AD早期识别的生物标记以及是否可以预测轻度认知损害(MCI)的转化尚需进一步验证,并且海马影像组学特征是否有其神经生物学基础也需要进一步探索.本文的主要目的是研究海马的影像组学特征是否可以作为AD早期识别的影像学标记.为此,我们利用最常用的多变量分类器对AD(261例)和正常人(231例)进行独立中心识别的交叉验证,6个中心的平均准确率为88.21%,更进一步,利用完全独立的ADNI数据集(1228例被试)也验证了这一结果.通过对MCI人群的系统研究发现,部分重要海马影像组学特征与被试的生物学评分(主要包括APOE基因型、多基因风险分数、脑脊液的生物标记物Aβ和Tau,以及认知能力的变化等)具有显著的相关性.更为重要的是,通过5年左右的纵向跟踪研究发现影像组学特征的变化与认知水平的变化具有高度一致性.本研究结果表明海马的影像组学特征有希望用于早期识别AD,具有预测MCI病人是否会转化为AD的潜在能力.综上,研究结果将有可能应用于MCI和AD的早期辅助识别,具有重要的临床意义.

Expert Consensus on the Care and Management of Patients with Cognitive Impairment in China

The cognitive disease consensus was prepared by panels of health and public representatives based on actual clinical practice in Geriatric Departments in Chinese hospitals and a systematic literature review. This consensus reflects the medical knowledge accumulated by those experts and provides information about professional medical care and advice.A multidisciplinary panel of specialists(neurologists,psychiatrists, and nursing specialists) reports an expert consensus on the medical knowledge accumulated from those experts and provides information about professional medical care and advice. The recommendations focus on the care and management of older adults with mild cognitive impairment,the objectives and methods of maintaining cognition and training, the assessments and measures of daily care for patients at different stages of dementia, the assessments and coping strategies for the behavioral and psychological symptoms of dementia, principles and suggestions for an appropriate living environment, arrangements for recreational activities, the care and management of patients with endstage dementia, and suggestions for addressing stress in caregivers.

ASAF: altered spontaneous activity fingerprinting in Alzheimer’s disease based on multisite fMRI

Several monocentric studies have noted alterations in spontaneous brain activity in Alzheimer's disease (AD), although there is no consensus on the altered amplitude of low-frequency fluctuations in AD patients. The main aim of the present study was to identify a reliable and reproducible abnormal brain activity pattern in AD. The amplitude of local brain activity (AM), which can provide fast mapping of spontaneous brain activity across the whole brain, was evaluated based on multisite rs-fMRI data for 688 subjects (215 normal controls (NCs), 221 amnestic mild cognitive impairment (aMCI) 252 AD). Two-sample t-tests were used to detect group differences between AD patients and NCs from the same site. Differences in the AM maps were statistically analyzed via the Stouffer's meta-analysis. Consistent regions of lower spontaneous brain activity in the default mode network and increased activity in the bilateral hippocampus/parahippocampus, thalamus, caudate nucleus, orbital part of the middle frontal gyrus and left fusiform were observed in the AD patients compared with those in NCs. Significant correlations (P?<?0.05, Bonferroni corrected) between the normalized amplitude index and Mini-Mental State Examination scores were found in the identified brain regions, which indicates that the altered brain activity was associated with cognitive decline in the patients. Multivariate analysis and leave-one-site-out cross-validation led to a 78.49% prediction accuracy for single-patient classification. The altered activity patterns of the identified brain regions were largely correlated with the FDG-PET results from another independent study. These results emphasized the impaired brain activity to provide a robust and reproducible imaging signature of AD.

Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns(With video)

Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.