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Background: Anosognosia, or unawareness of memory deficits, is a common manifestation of Alzheimer’s disease (AD), but greatly variable in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) subjects. Self-referential network (SRN) is responsible for self-referential processing and considered to be related to AD progression. Objective: Our aim is to explore connectivity changes of SRN and its interaction with memory-related network and primary sensorimotor network (SMN) in the AD spectrum. Methods: About 444 Alzheimer’s Disease Neuroimaging Initiative subjects (86 cognitively normal [CN]; 156 SCD; 146 aMCI; 56 AD) were enrolled in our study. The independent component analysis (ICA) method was used to extract the SRN, SMN, and memory-related network from all subjects. The alteration of functional connectivity (FC) within SRN and its connectivity with memory-related network/SMN were compared among four groups and further correlation analysis between altered FC and memory awareness index as well as episodic memory score were performed. Results: Compared with CN group, individuals with SCD exhibited hyperconnectivity within SRN, while aMCI and AD patients showed hypoconnectivity. Furthermore, aMCI patients and AD patients both showed the interruption of the FC between the SRN and memory-related network compared to CN group. Pearson correlation analysis showed that disruptive FC within SRN and its interaction with memory-related network were related to memory awareness index and episodic memory scores. Conclusion: In conclusion, impaired memory awareness and episodic memory in the AD spectrum are correlated to the disconnection within SRN and its interaction with memory-related network.

Background: Voxel-based morphometry studies have not yielded consistent results among patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Objective: Therefore, we aimed to conduct a meta-analysis of gray matter (GM) abnormalities acquired from these studies to determine their respective neuroanatomical changes. Methods: We systematically searched for voxel-based whole-brain morphometry studies that compared MCI or SCD subjects with healthy controls in PubMed, Web of Science, and EMBASE databases. We used the coordinate-based method of activation likelihood estimation to determine GM changes in SCD, MCI, and MCI sub-groups (amnestic MCI and non-amnestic MCI). Results: A total of 45 studies were included in our meta-analysis. In the MCI group, we found structural atrophy of the bilateral hippocampus, parahippocampal gyrus (PHG), amygdala, right lateral globus pallidus, right insula, and left middle temporal gyrus. The aMCI group exhibited GM atrophy in the bilateral hippocampus, PHG, and amygdala. The naMCI group presented with structural atrophy in the right putamen, right insula, right precentral gyrus, left medial/superior frontal gyrus, and left anterior cingulate. The right lingual gyrus, right cuneus, and left medial frontal gyrus were atrophic GM regions in the SCD group. Conclusion: Our meta-analysis identified unique patterns of neuroanatomical alternations in both the MCI and SCD group. Structural changes in SCD patients provide new evidence for the notion that subtle impairment of visual function, perception, and cognition may be related to early signs of cognitive impairment. In addition, our findings provide a foundation for future targeted interventions at different stages of preclinical Alzheimer’s disease.

Background Human motor imagery (MI), action execution, and action observation (AO) are functionally considered as equivalent. MI during AO can extensively induce activation of motor-related brain network in the absence of overt movement. The magnetoencephalography (MEG) provides an important technology to reveal and reflect human brain information processing in multi-frequency bands. Utilizing a MEG system, we aimed to quantitatively investigate the frequency-specific equivalent characteristics in brain processing patterns between MI during AO and action execution in multi-frequency bands, including delta, theta, alpha, beta, gamma, and high-frequency oscillations. Methods A total of 12 healthy subjects were studied with a whole-head MEG system during finger movement and MI during finger movement observation. We analyzed the brain activities in multi-frequency ranges of 1 Hz to 200 Hz. Results Both MI during AO and action execution evoked the distinctive brain activities in low frequency ranges (i.e. delta, theta, and alpha). Significant differences were found in global spectral power between finger movement and MI during AO in delta and alpha oscillations. Compared with finger movement, delta (1-4 Hz) oscillation power in MI during AO were obviously decreased in left and right frontals and occipitals, and theta (4-8 Hz) and alpha (8-13 Hz) oscillation power were obviously increased in frontal, parietal and occipital. Conclusion MEG power evoked by finger movement and MI during AO is mainly concentrated in the energy distribution below 13 Hz. Furthermore, finger movement and MI during AO might share frequency-specific equivalence of brain neural activation dependent on different MEG frequency ranges.

Aims Both amnestic mild cognitive impairment (aMCI) and remitted late‐onset depression (rLOD) confer a high risk of developing Alzheimer's disease (AD). This study aims to determine whether the Characterizing AD Risk Events (CARE) index model can effectively predict conversion in individuals at high risk for AD development either in an independent aMCI population or in an rLOD population. Methods The CARE index model was constructed based on the event‐based probabilistic framework fusion of AD biomarkers to differentiate individuals progressing to AD from cognitively stable individuals in the aMCI population (27 stable subjects, 6 progressive subjects) and rLOD population (29 stable subjects, 10 progressive subjects) during the follow‐up period. Results AD diagnoses were predicted in the aMCI population with a balanced accuracy of 80.6%, a sensitivity of 83.3%, and a specificity of 77.8%. They were also predicted in the rLOD population with a balanced accuracy of 74.5%, a sensitivity of 80.0%, and a specificity of 69.0%. In addition, the CARE index scores were observed to be negatively correlated with the composite Z scores for episodic memory (R 2 = .17, P

Glioma can cause variable alterations to the structure and function of the brain. However, there is a paucity of studies on the gray matter (GM) volume alterations in the brain region opposite the temporal glioma before and after surgery. Therefore, the present study was initiated to investigate the alternation in contralateral homotopic GM volume in patients with unilateral temporal lobe glioma and further, assess the relationship between GM volume alternations with cognition. Eight left temporal lobe glioma patients (LTPs), nine right temporal lobe glioma patients (RTPs), and 28 demographically matched healthy controls (HCs) were included. Using voxel‐based morphometry method, alternations in the contralateral homotopic GM volume in patients with unilateral temporal lobe glioma was determined. Furthermore, the correlation analysis was performed to explore the relationship between cognitive function and altered GM volume. In the preoperative analysis, compared to HCs, LTPs exhibited increased GM volume in right inferior temporal gyrus and right temporal pole (superior temporal gyrus), and, RTPs presented increased GM volume in left inferior temporal gyrus. In the postoperative analysis, compared to HCs, RTPs presented increased GM volume in left middle temporal gyrus. Furthermore, the increased GM volume was significantly positively correlated with the memory test but negatively correlated with the visuospatial test. This study preliminarily confirmed that there were compensatory changes in the GM volume in the contralateral temporal lobe in unilateral temporal lobe glioma patients. Furthermore, alterations of GM volume may be a mechanism for cognitive function compensation.

Background Patients with frontal glioma might experience cognition alterations together with potential dysfunction of resting-state networks (RSNs). To understand the altered patterns of the intrinsic activity and underlying network interactions between the cognitive-related RSNs is of great importance. Objective This study aimed to investigate the characteristics of the altered RSNs, including default mode network, executive control network, and salience network and further elucidate the possible functional reorganization of RSNs in patients with frontal glioma. Methods Thirteen patients with frontal glioma and 10 healthy controls (HCs) were enrolled in this study. Independent component analysis was performed to identify the characteristics of the selected RSNs activity. Further, functional connectivity analysis was applied to investigate the relationship between the altered regions. Subsequently, partial correlation analysis was performed to examine associations between the neural activity of RSNs and neurocognitive characteristics. Results Compared with the HCs group, the patient group exhibited significant differences in functional connectivity among default mode network, executive control network, and salience network. In addition, the number of the significant functional connectivities between the paired seeds observed in the patients was greater than that in HCs and significantly increased functional connectivity was detected between left posterior cingulate cortex and right angular gyrus. Furthermore, altered neural activities in the RSNs of patients with frontal glioma were positively associated with certain aspects of cognitive function. Conclusions Our results suggested underlying network functional reorganization of the triple unifying RSNs in patients with frontal glioma, providing novel insights for improving understanding of brain function.

According to recent criteria of classification, amnestic mild cognitive impairment (aMCI) could be divided into two categories: single-domain aMCI (sd-aMCI) and multiple-domain aMCI (md-aMCI). The difference between sd-aMCI and md-aMCI needs further exploration. The present study aimed to compare deficits in visuospatial working memory (VSWM) and executive function between sd-aMCI versus md-aMCI patients by use of event-related potentials (ERP) and standardized low-resolution brain electromagnetic tomography analysis (sLORETA).The ERP data were measured and analyzed in 26 sd-aMCI, 13 md-aMCI patients and 46 healthy elderly controls (HEC) during VSWM and Go/Nogo processes.During VSWM task, md-aMCI patients showed decreased P300 amplitude compared to HEC and sd-aMCI patients (All p 0.05). As compared to sd-aMCI, md-aMCI showed a hypoactivation in the right middle frontal gyrus in 1-back task during the P300 time range. During the Go/Nogo task, sd-aMCI and md-aMCI patients showed reduced N200 amplitude, compared to HEC (All p 0.05). However, md-aMCI patients had decreased N200 amplitude, with respect to sd-aMCI patients. Further, as compared to sd-aMCI patients, md-aMCI patients showed a hypoactivation in the right superior frontal gyrus during the N200 time range.These findings with a combined ERP and sLORETA study showed more severe deficits in updating operations of WM, detections of the target stimulus and conflict processes in md-aMCI, compared to sd-aMCI patients.The present study showed that a combined ERP and sLORETA study during the VSWM and Go/Nogo tasks could distinguish md-aMCI from sd-aMCI.

Remitted late-life depression (rLLD) and amnestic mild cognitive impairment (aMCI) are both associated with a high risk of developing Alzheimer's disease (AD). Neurodegeneration is considered to spread within pre-existing networks. To investigate whether, in the healthy brain, there was a pre-existing cross-network between the intrinsic networks that are vulnerable to rLLD and aMCI. We performed functional connectivity analyses based on brain areas with the greatest brain neuronal activity differences in 55 rLLD, 87 aMCI, and 114 healthy controls. Intrinsic networks that were differentially vulnerable to rLLD and aMCI converged onto the sensory-motor network (SMN) in the healthy brain. These regions in the SMN within the aMCI- and rLLD-vulnerable networks played different roles in the cognitive functions. This study identifies the SMN as a cross-network between rLLD- and aMCI-vulnerable networks. The common susceptibility of these diseases to AD is likely due to the breakdown of the cross-network. The results further suggest that interventions targeting the amelioration of sensory-motor deficits in the early course of disease in individuals with AD risk may enhance patient function as AD pathology progresses.

We aimed to investigate the genetic mechanisms associated with coronavirus disease of 2019 (COVID-19) outcomes in the host and to evaluate the possible associations between smoking and drinking behavior and three COVID-19 outcomes: severe COVID-19, hospitalized COVID-19 and COVID-19 infection. We described the genomic loci and risk genes associated with the COVID-19 outcomes, followed by functional analyses of the risk genes. Then, a summary data-based Mendelian randomization (SMR) analysis, and a transcriptome-wide association study (TWAS) were performed for the severe COVID-19 dataset. A two-sample Mendelian randomization (MR) analysis was used to evaluate the causal associations between various measures of smoking and alcohol consumption and the COVID-19 outcomes. A total of 26 protein-coding genes, enriched in chemokine binding, cytokine binding and senescence-related functions, were associated with either severe COVID-19 or hospitalized COVID-19. The SMR and the TWAS analyses highlighted functional implications of some GWAS hits and identified seven novel genes for severe COVID-19, including CCR5, CCR5AS, IL10RB, TAC4, RMI1 and TNFSF15, some of which are targets of approved or experimental drugs. According to our studies, increasing consumption of cigarettes per day by 1 standard deviation is related to a 2.3-fold increase in susceptibility to severe COVID-19 and a 1.6-fold increase in COVID-19-induced hospitalization. Contrarily, no significant links were found between alcohol consumption or binary smoking status and COVID-19 outcomes. Our study revealed some novel COVID-19 related genes and suggested that genetic liability to smoking may quantitatively contribute to an increased risk for a severe course of COVID-19.

Based on artificial intelligence (AI), computer-assisted medical diagnosis can scientifically and efficiently deal with a large quantity of medical imaging data. AI technologies including deep learning have shown remarkable progress across medical image recognition and genome analysis. Imaging-genomics attempts to explore the associations between potential gene expression patterns and specific imaging phenotypes. These associations provide potential cellular pathophysiology information, allowing sampling of the lesion habitat with high spatial resolution. Glioblastoma (GB) poses spatial and temporal heterogeneous characteristics, challenging to current precise diagnosis and treatments for the disease. Imaging-genomics provides a powerful tool for non-invasive global assessment of GB and its response to treatment. Imaging-genomics also has the potential to advance our understanding of underlying cancer biology, gene alterations, and corresponding biological processes. This article reviews the recent progress in the utilization of the imaging-genomics analysis in GB patients, focusing on its implications and prospects in individualized diagnosis and management.

Anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a rare autoimmune disease that is characterized by acute cognitive impairment, mental symptoms, and seizures. The high comorbidity rate between anti–AMPA receptor (AMPAR) encephalitis and other somatic diseases, such as malignancy, has revealed the possibility of potential copathogenesis. However, there have not yet been reports about anti-AMPAR encephalitis with concomitant cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer disease (AD). Herein, we present the case of an elderly male patient with autoimmune encephalitis (AE) presenting with anti–AMPA1-R and anti–AMPA2-R antibodies, as well as CSF biomarkers of AD. The patient was hospitalized with acute memory decline for 1 week. Anti–AMPA1-R and anti–AMPA2-R antibodies were positively detected in CSF, and the anti–AMPA2-R antibody was also present in the serum. Additionally, the biomarkers of AD were concurrently present in CSF (Aβ1−42 = 245.70 pg/mL, t-Tau = 894.48 pg/mL, p-Tau = 78.66 pg/mL). After administering a combined treatment of intravenous immunoglobulin and glucocorticoids, the patient recovered significantly, and his cognitive function achieved a sustained remission during 2 months' follow-up. This case raises the awareness of a possible interaction between AE and changes of CSF biomarkers. We speculated that the existence of AMPAR antibodies can induce changes of CSF, and other pathological alterations. This present report highlights that a potential relationship exists among AE and provides a warning when making the diagnosis of AD.

Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Amnestic MCI (aMCI) and non-amnestic MCI are the two subtypes of MCI with the former having a higher risk for progressing to Alzheimer's disease (AD). Compared with healthy elderly adults, individuals with MCI have specific functional alterations in the salience network (SN). However, no consistent results are documenting these changes. This meta-analysis aimed to investigate the specific functional alterations in the SN in MCI and aMCI.Methods: We systematically searched PubMed, Embase, and Web of Science for scientific neuroimaging literature based on three research methods, namely, functional connectivity (FC), regional homogeneity (ReHo), and the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF). Then, we conducted the coordinate-based meta-analysis by using the activation likelihood estimation algorithm.Results: In total, 30 functional neuroimaging studies were included. After extracting the data and analyzing it, we obtained specific changes in some brain regions in the SN including decreased ALFF/fALFF in the left superior temporal gyrus, the insula, the precentral gyrus, and the precuneus in MCI and aMCI; increased FC in the thalamus, the caudate, the superior temporal gyrus, the insula, and the cingulate gyrus in MCI; and decreased ReHo in the anterior cingulate gyrus in aMCI. In addition, as to FC, interactions of the SN with other networks including the default mode network and the executive control network were also observed mainly in the middle frontal gyrus and superior frontal gyrus in MCI and inferior frontal gyrus in aMCI.Conclusions: Specific functional alternations in the SN and interactions of the SN with other networks in MCI could be useful as potential imaging biomarkers for MCI or aMCI. Meanwhile, it provided a new insight in predicting the progression of health to MCI or aMCI and novel targets for proper intervention to delay the progression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42020216259].

Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures.Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI).Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity.Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

We investigated the relationship between neuroticism and 16 mental and 18 physical traits using summary results of genome-wide association studies for these traits. LD score regression was used to investigate genetic correlations between neuroticism and the 34 health outcomes. Mendelian randomization was performed to investigate mutual causal relationships between neuroticism and the 34 health outcomes. Neuroticism genetically correlates with a majority of health-related traits and confers causal effects on 12 mental traits (major depressive disorder (MDD), insomnia, subjective well-being (SWB, negatively), schizophrenia, attention-deficit/hyperactivity disorder, alcohol dependence, loneliness, anorexia nervosa, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, and psychiatric disorders) and two physical diseases (cardiovascular disease and hypertensive disease). Conversely, MDD, SWB, and insomnia have a causal effect on neuroticism. We highlighted key genes contributing to the causal associations between neuroticism and MDD, including RBFOX1, RERE, SOX5, and TCF4, and those contributing to the causal associations between neuroticism and cardiovascular diseases, including MAD1L1, ARNTL, RERE, and SOX6. The present study indicates that genetic variation mediates the causal influences of neuroticism on mental health and cardiovascular diseases.

BackgroundSubjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

Background: Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive. Method: This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR). Results: In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data. Conclusion: The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.

The insula, consisting of functionally diverse subdivisions, plays a significant role in Parkinson’s disease (PD)-related cognitive disorders. However, the functional connectivity (FC) patterns of insular subdivisions in PD remain unclear. Our aim is to investigate the changes in FC patterns of insular subdivisions and their relationships with cognitive domains. Three groups of participants were recruited in this study, including PD patients with mild cognitive impairment (PD-MCI, n = 25), PD patients with normal cognition (PD-NC, n = 13), and healthy controls (HCs, n = 17). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in insular subdivisions of the three groups. Moreover, all participants underwent a neuropsychological battery to assess cognition so that the relationship between altered FC and cognitive performance could be elucidated. Compared with the PD-NC group, the PD-MCI group exhibited increased FC between the left dorsal anterior insular (dAI) and the right superior parietal gyrus (SPG), and altered FC was negatively correlated with memory and executive function. Compared with the HC group, the PD-MCI group showed significantly increased FC between the right dAI and the right median cingulate and paracingulate gyri (DCG), and altered FC was positively related to attention/working memory, visuospatial function, and language. Our findings highlighted the different abnormal FC patterns of insular subdivisions in PD patients with different cognitive abilities. Furthermore, dysfunction of the dAI may partly contribute to the decline in executive function and memory in early drug-naïve PD patients.

PurposeTo extract texture features from magnetic resonance imaging (MRI) scans of patients with brain tumors and use them to train a classification model for supporting an early diagnosis.MethodsTwo groups of regions (control and tumor) were selected from MRI scans of 40 patients with meningioma or glioma. These regions were analyzed to obtain texture features. Statistical analysis was conducted using SPSS (version 20.0), including the Shapiro–Wilk test and Wilcoxon signed-rank test, which were used to test significant differences in each feature between the tumor and healthy regions. T-distributed stochastic neighbor embedding (t-SNE) was used to visualize the data distribution so as to avoid tumor selection bias. The Gini impurity index in random forests (RFs) was used to select the top five out of all features. Based on the five features, three classification models were built respectively with three machine learning classifiers: RF, support vector machine (SVM), and back propagation (BP) neural network.ResultsSixteen of the 25 features were significantly different between the tumor and healthy areas. Through the Gini impurity index in RFs, standard deviation, first-order moment, variance, third-order absolute moment, and third-order central moment were selected to build the classification model. The classification model trained using the SVM classifier achieved the best performance, with sensitivity, specificity, and area under the curve of 94.04%, 92.3%, and 0.932, respectively.ConclusionTexture analysis with an SVM classifier can help differentiate between brain tumor and healthy areas with high speed and accuracy, which would facilitate its clinical application.

Background Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and three kinds of depressive phenotypes, namely, MDD, depressed affect (DAF), and depression (DEP, including both MDD and the broad definition of depression). Methods Genetic correlations between PTSD and the depressive phenotypes were tested using linkage disequilibrium score regression. Polygenic overlap analysis was used to estimate shared and trait-specific causal variants across a pair of traits. Causal relationships between PTSD and the depressive phenotypes were investigated using Mendelian randomization. Shared genomic loci between PTSD and MDD were identified using cross-trait meta-analysis. Results Genetic correlations of PTSD with the depressive phenotypes were in the range of 0.71~0.80. The estimated numbers of causal variants were 14,565, 12,965, 10,565, and 4,986 for MDD, DEP, DAF, and PTSD, respectively. In each case, causal variants contributing to PTSD were completely or largely covered by causal variants defining each of the depressive phenotypes. Mendelian randomization analysis indicates that the genetically determined depressive phenotypes confer a causal effect on PTSD (b = 0.21~0.31). Notably, genetically determined PTSD confers a causal effect on DEP (b = 0.14) and DAF (b = 0.15), but not MDD. Cross-trait meta-analysis of MDD and PTSD identifies 47 genomic loci, including 29 loci shared between PTSD and MDD. Conclusion Evidence from shared genetics suggests that PTSD is a subtype of MDD. This study provides support to the efforts in reducing diagnostic heterogeneity in psychiatric nosology. Funding The National Key Research and Development Program of China (2018YFC1314300) and the National Natural Science Foundation of China (81471364 and 81971255).

Background Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer's disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI. Methods We collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously. Results Compared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increased feeder connectivity and decreased local connectivity of the diverse club compared with the SCD group. The overlapping nodes of the rich club and diverse club showed a significant difference in nodal efficiency and shortest path length (L p) between groups. Notably, the L p values of overlapping nodes in the SCD and aMCI groups were significantly associated with episodic memory. Conclusion The present study demonstrates that the network properties of SCD and aMCI have varying degrees of damage. The combination of the rich club and the diverse club can provide a novel insight into the pathological mechanism of the AD spectrum. The altered patterns in overlapping nodes might be potential biomarkers in the diagnosis of the AD spectrum.

Background: Mild cognitive impairment (MCI) is regarded as a transitional stage between normal aging and Alzheimer's disease (AD) dementia. MCI individuals with deficits in executive function are at higher risk for progressing to AD dementia. Currently, there is no consistent result for alterations in the executive control network (ECN) in MCI, which makes early prediction of AD conversion difficult. The aim of the study was to find functional MRI-specific alterations in ECN in MCI patients by expounding on the convergence of brain regions with functional abnormalities in ECN. Methods: We searched PubMed, Embase, and Web of Science to identify neuroimaging studies using methods including the amplitude of low frequency fluctuation/fractional amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in MCI patients. Based on the Activation Likelihood Estimation algorithm, the coordinate-based meta-analysis and functional meta-analytic connectivity modeling were conducted. Results: A total of 25 functional imaging studies with MCI patients were included in a quantitative meta-analysis. By summarizing the included articles, we obtained specific brain region changes, mainly including precuneus, cuneus, lingual gyrus, middle frontal gyrus, posterior cingulate cortex, and cerebellum posterior lobe, in the ECN based on these three methods. The specific abnormal brain regions indicated that there were interactions between the ECN and other networks. Conclusions: This study confirms functional imaging specific abnormal markers in ECN and its interaction with other networks in MCI. It provides novel targets and pathways for individualized and precise interventions to delay the progression of MCI to AD.

Objective Previous studies suggested likely mechanisms underlying the dysfunction of the default mode network (DMN) in schizophrenia. However, altered patterns of the intrinsic activity of the DMN in both deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients, as well as the neurocognitive relationships among them, remain unknown. This study explores the resting-state characteristics of the DMN activity in both DS and NDS patients, and further investigates correlations with neurocognitive features. Methods Demographic, resting-state functional MRI, and neurocognitive data were collected in 37 DS and 38 NDS patients, as well as in 38 matched healthy control subjects (HCs). Independent component analysis was conducted to investigate the characteristics of DMN activity and to further distinguish between common and specific altered regions. In addition, partial correlation analysis was conducted to examine associations between the activity of altered regions and neurocognitive assessments. Results Overlapping altered brain activity was observed in both DS and NDS patients in the left middle frontal gyrus (MFG), the left angular gyrus (ANG), and the calcarine sulcus (CAL) region. Furthermore, compared to HCs, DS patients showed less activity in the right inferior temporal gyrus, the right para-hippocampal gyrus / hippocampus (PHP / HIP), and the left precuneus (PCUN), while they showed increased activity in the posterior cingulate cortex (PCC). Notably, NDS patients showed less activity in the bilateral middle occipital gyrus. Correlation analysis indicated that, in the DS group, both Trail Making Test (TMT)-B and spatial processing scores were positively associated with the activities of the left PCUN and the right PHP / HIP, while the Stroop color scores were negatively associated with PCC activity. In the NDS group, the TMT-B scores were associated with activities of the left MFG and CAL regions, while the scores of the Wechsler adult intelligence scale (Chinese revision) were negatively associated with CAL region activity. Conclusion The present study demonstrates convergent and divergent altered patterns of the DMN in both DS and NDS patients. Importantly, the specific altered regions of the DMN in DS patients may be associated with extensive deficient neurocognition, indicating novel insights into the pathogenesis of cognitive impairment in schizophrenia.

Background: The cognitive control network (CCN) is widely considered to be a frontoparietal circuit that is involved in executive function. This study aimed to investigate the structural and functional plasticity within the CCN in unilateral frontal gliomas, which are associated with the protection of executive functions. Methods: To detect structural and functional changes within the CCN, we measured gray matter (GM) volume, regional homogeneity, the amplitude of low-frequency fluctuation (ALFF), degree centrality, and functional connectivity within the CCN in 37 patients with gliomas invading the left frontal lobe (n = 16) or the right frontal lobe (n = 21) and 40 healthy controls (CNs). Partial correlation analysis was performed to assess the association between the altered structural and functional indices and executive function. Results: When the tumor invaded the left frontal lobe, the patients showed reduced ALFF in the dorsal medial prefrontal cortex (dmPFC) within the CCN and increased ALFF in the right superior parietal cortex (rSP) within the CCN compared to the CNs. When the tumor invaded the right frontal lobe, the patients showed significantly increased GM volume and ALFF in the left superior parietal cortex (lSP) within the CCN compared to the CNs. Furthermore, the patients showed significantly increased functional connectivities between the lSP and the dmPFC and between the lSP and the rSP within the CCN compared to the CNs. Increased ALFF in the lSP within the CCN was positively correlated with executive function. Conclusions: Tumors invading the frontal lobe induced contralesional structural and functional reorganization within the posterior CCN in patients with unilateral frontal gliomas. This further suggests that the contralesional superior parietal cortex acts as a functional compensation hub within the CCN, which may protect it against the detrimental effects of tumor invasion on executive functions.

Objective This study aimed to investigate the characteristic of brain structural connections in glioma patients and further evaluate the relationship between changes in the white matter tracts and cognitive decline. Methods This retrospective study included a total of 35 subjects with glioma and 14 demographically matched healthy controls, who underwent diffusion tensor imaging scans and formal neuropsychological assessment tests. Fractional anisotropy (FA) values of white matter tracts were derived from atlas‐based analysis to compare group differences. Furthermore, subgroup‐level analysis was performed to differentiate the effects of tumor location on white matter tracts. Partial correlation analysis was used to examine the associations between neurocognitive assessments and the integrity of tracts. Region of interest‐based network analysis was performed to validate the alteration of structural brain network in subjects with glioma. Results Compared with controls, subjects with glioma exhibited reduced FA values in the right uncinate fasciculus. Besides, subjects with glioma exhibited worse performance in several cognitive assessments. Partial correlation analysis indicated that the FA value in the right superior longitudinal fasciculus temporal part was significantly positively correlated with scores of visual–spatial abilities in subjects with glioma in the right temporal lobe (r = .932, p = .002). Region of interest‐based network analysis revealed that subjects with glioma exhibited reduced FA, fiber length (FL), and fiber number (FN) between specific brain regions compared with controls. Conclusion The present study demonstrated the reduced integrity of white matter tracts and altered structural connectivity in brain networks in patients with glioma. Notably, white matter tracts in the right hemisphere might be vulnerable to the effects of a frontal or temporal lesion and might be associated with deficient cognitive function., In this work, we explored the effect of the heterogeneous gliomas on multiple WM tracts and global structural network. We attempted to utilize tract‐based DTI analysis to identify the alteration of the white matter (WM) tracts in patients with glioma. The cognitive characteristics of the patients with glioma also studied.

BackgroundAmnestic mild cognitive impairment (aMCI) is characterized by delayed P300 latency and reduced grey matter (GM) volume, respectively. The relationship between the features in aMCI is unclear. This study was to investigate the relationship between the altered P300 latency and the GM volume in aMCI.MethodsThirty-four aMCI and 34 well-matched normal controls (NC) were studied using electroencephalogram during a visual oddball task and scanned with MRI. Both tests were finished in the same day.ResultsAs compared with the NC group, the aMCI group exhibited delayed P300 latency in parietal cortex and reduced GM volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus. A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group. Interestingly, the mediating analysis found P300 latency significantly mediated the association between right supramarginal gyrus volume and information processing speed indicated by Stroop Color and Word Test A scores.ConclusionsThe association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.

To identify risk factors for predicting posttraumatic hydrocephalus (PTH) development after traumatic brain injury in patients who underwent decompressive craniectomy (DC).This retrospective study included 121 patients who underwent DC performed by 6 different neurosurgeons after traumatic brain injury between January 2013 and December 2016 at Yijishan Hospital and were still alive at 6-month follow-up. Patients were divided into PTH group and non-PTH group. Logistic regression analysis was used to identify PTH potential risk factors based on results obtained from univariate analysis. Power of the regression model to discriminate PTH from non-PTH was evaluated using receiver operating characteristic curve.With Glasgow Coma Scale (GCS) score cutoff value of 6, GCS scores6 on admission, craniectomy site, and intraventricular hemorrhage (IVH) were significant predictors for development of PTH after DC. Receiver operating characteristic curve indicated that a final predictive model composed of these 3 factors (area under the curve [AUC] = 0.866, sensitivity = 0.78, and specificity = 0.83) was significantly better than each single model (AUC = 0.750 for GCS scores on admission, AUC = 0.650 for craniectomy site, AUC = 0.572 for IVH). A significantly positive association was found between patients' Glasgow Outcome Scale Extended scores and GCS scores on admission, whereas a significantly negative association was found between IVH, craniectomy site, and Glasgow Outcome Scale Extended.GCS scores6 on admission, presence of IVH on first head computed tomography scan, and need for bilateral DC might be used to predict whether patients with traumatic brain injury after DC will develop PTH. The reliability of this specific combination might be useful for clinicians to make a correct prediction.

Objectives The study aimed to investigate and compare the effect of cognitive reserve (CR) on brain activation in healthy controls (HC) and amnestic mild cognitive impairment (aMCI) patients during 0-back and 1-back tasks measured by event-related potential (ERP). Methods The study recorded 85 subjects (39 aMCI patients and 46 their matched controls) with a 64-channel electroencephalogram (EEG). Subjects performed 0- and 1-back tasks. Results Compared to HC, aMCI patients showed reduced accuracy, delayed mean correct response time (RT) and decreased P300 amplitude at central-parietal and parietal electrodes. A mediation analysis indicated that higher CR reduced neural inefficiency, which might be associated with better task performance in HC. However, no correlation was detected between CR and neural inefficiency in aMCI patients, whereas higher CR was still related to enhanced accuracy and prolonged RT in aMCI patients. Conclusions The present study reported that higher CR could contribute to better task performance via down-regulating neural inefficiency in HC. In addition, higher CR might modulate attention processes in aMCI via a way distinct from that in HC, and eventually result in better task performance. Significance The study provided evidence for that improving CR might lower cognitive impairment of healthy elderly and aMCI patients.

Objectives: Gliomas are widely considered to be related to the altered topological organization of functional networks before operations. Tumors are usually thought to cause multimodal cognitive impairments. The structure is thought to form the basics of function, and the aim of this study was to reveal the rich-club organization and topological patterns of white matter (WM) structural networks associated with cognitive impairments in patients with frontal and temporal gliomas. Methods: Graph theory approaches were utilized to reveal the global and regional topological organization, and rich-club organization of WM structural networks of 14 controls (CN), 13 frontal tumors (FTumor), and 18 temporal tumors (TTumor). Linear regression was used to assess the relationship between cognitive performances and altered topological parameters. Results: When compared with CN, both FTumor and TTumor showed no alterations in small-world properties and global network efficiency, but instead showed altered local network efficiency. Secondly, FTumor and TTumor patients showed similar deficits in the nodal shortest path in the left rolandic operculum, and degree centrality (DC) of the right dorsolateral and medial superior frontal gyrus (SFGmed). Thirdly, compared to FTumor patients, TTumor patients showed a significantly higher DC in the right dorsolateral and SFGmed, a higher level of betweenness in the right SFGmed, and higher nodal efficiency in the left middle frontal gyrus and right SFGmed. Finally, rich club organization was disrupted, with increased structural connectivity among rich club nodes and reduced structural connectivity among peripheral nodes, in FTumor and TTumor patients. Altered local efficiency in TTumor correlated with memory function while altered local efficiency in FTumor correlated with the information processing speed. Conclusion: Both FTumor and TTumor presented an intact global topology and altered regional topology related to cognitive impairment and may also share the convergent and divergent regional topological organization of WM structural networks. This suggested that a compensatory mechanism plays a key role in global topology formation in both FTumor and TTumor patients and as such, development of a structural connectome for patients with brain tumors would be an invaluable medical resource and allow clinicians to make comprehensive pre-operative planning.

Dementia with Lewy bodies (DLB) is characterized by the transient fluctuating cognition and recurrent visual hallucinations, which may be caused by disorders of the intrinsic brain network dynamics. However, little is known regarding the dynamic features of the brain network behind these symptoms in DLB. In the present study, the intra- and inter-brain network dynamics were explored on a time scale in 17 DLB and 20 healthy controls (HC) applying a sliding-window method followed by k-means clustering analysis. To further evaluate the impact of network dynamics on brain performance, the local and global efficiency of the brain network was calculated. Compared with HC, the dynamic functional connectivity variation matrix in DLB patients was represented by a mixed change of intra-network increase and inter-network decrease. DLB patients devoted more time to a negative connectivity pattern, which represents a state of functional separation. Furthermore, the local efficiency of DLB patients was significantly lower compared with HC. These observations indicate an altered dynamic variability and disorders to the time allocation of state sequences in DLB, which might result in a disturbance of the intricate brain network dynamic properties, thereby leading to a lack of integration and flexibility and an ineffective brain function. In conclusion, dynamic functional connectivity analysis could identify differences between DLB and HC, providing evidences for DLB diagnosis and contributing to the understanding of the widespread clinical features and complex treatment strategies in DLB patients.

OBJECTIVEThis study aimed to explore the contralesional homotopic functional plasticity in the brain of patients with unilateral temporal glioma.METHODSDemographic, neurocognitive, and resting-state functional MRI data were collected from 17 patients with temporal glioma (10 in the right lobe and 7 in the left lobe), along with 14 age- and sex-matched healthy controls. The amplitude of low-frequency fluctuation (ALFF) of the contralesional homotopic region and 2 control regions was examined. The region-of-interest–based analysis was used to determine the altered functional connectivity (FC) of the contralesional homotopic region, showing significantly different intrinsic regional brain activity between patients and controls. Partial correlation analysis was conducted to determine the association between the altered neural activity and behavioral characteristics.RESULTSCompared with controls, patients with right temporal glioma exhibited significantly increased ALFF in the contralesional homotopic hippocampus and parahippocampal region. In addition, the intrinsic regional activity in these regions was negatively correlated with the visuospatial score (r = −0.718, p = 0.045). Whole-brain FC analysis revealed significantly increased FC between the left hippocampus and parahippocampal regions and the left inferior temporal gyrus, and decreased FC between the left hippocampus and parahippocampal regions and the left inferior frontal gyrus. No significant changes were found in the 2 control regions.CONCLUSIONSContralesional homotopic regions are instrumental in the process of neural plasticity and functional compensation observed in patients with unilateral temporal glioma. The observed findings might be used to help preoperative evaluation or rehabilitation of postsurgical patients.

Aphemia with pure word dumbness is a relatively rare clinical syndrome caused by injury to the Broca area of the dominant hemisphere. Patients with this syndrome have significant difficulties in oral expression, whereas other language functions, such as written expression and comprehension, are normal. In this study, a patient without no evidence of structural brain lesions presented with aphemia with pure word dumbness after head trauma of the frontal lobe. Through magnetic resonance imaging (MRI) examinations, functional abnormalities (regional homogeneity, degree centrality, and language network) were found in the patient without structural alterations. After four weeks of treatment with repetitive transcranial magnetic stimulation (rTMS) and cognitive evaluation every week, we found that the patient's linguistic function (i.e., spontaneous speech, speech comprehension, rehearsal, naming, reading, writing and the aphasia quotient) recovered gradually. Therefore, rTMS may be an adjuvant therapy for the recovery of aphemia patients with pure word dumbness.

Introduction Both remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). Objectives Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. Methods We used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). Results A reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)–control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN–CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. Conclusions These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD.

// Baoyu Yuan 1 , Jiu Chen 1 , Liang Gong 1 , Hao Shu 1 , Wenxiang Liao 1 , Zan Wang 1 , Duan Liu 1 , Chunming Xie 1 and Zhijun Zhang 1 1 Department of Neurology, ZhongDa Hospital, Neuropsychiatric Institute, Medical School of Southeast University, Nanjing, PR China Correspondence to: Zhijun Zhang, email: // Chunming Xie, email: // Keywords : amnestic mild cognitive impairment (aMCI), executive function (EF), episodic memory (EM), regional homogeneity (ReHo), functional magnetic resonance imaging (fMRI), Pathology Section Received : January 25, 2016 Accepted : July 18, 2016 Published : August 31, 2016 Abstract Deficits in episodic memory (EM) are a hallmark clinical symptom of patients with amnestic mild cognitive impairment (aMCI). Impairments in executive function (EF) are widely considered to exacerbate memory deficits and to increase the risk of conversion from aMCI to Alzheimer’s disease (AD). However, the specific mechanisms underlying the interaction between executive dysfunction and memory deficits in aMCI patients remain unclear. Thus, the present study utilized resting-state functional magnetic resonance imaging (fMRI) scans of the EF network and the EM network to investigate this relationship in 79 aMCI patients and 119 healthy controls (HC). The seeds were obtained from the results of a regional homogeneity (ReHo) analysis. Functional connectivity (FC) within the EM network was determined using a seed in the right retrosplenial cortex (RSC), and FC within EF network was assessed using seeds in the right dorsolateral prefrontal cortex (DLPFC). There was a significant negative correlation between EM scores and EF scores in both the aMCI and HC groups. Compared to the HC group, aMCI patients had reduced right RSC connectivity but enhanced right DLPFC connectivity. The overlapping brain regions between the EM and EF networks were associated with FC in the right inferior parietal lobule (IPL) in the right RSC network, and in the bilateral middle cingulate cortex (MCC) and left IPL in the right DLPFC network. A mediation analysis revealed that the EF network had an indirect positive effect on EM performance in the aMCI patients. The present findings provide new insights into the neural mechanisms underlying the interaction between impaired EF and memory deficits in aMCI patients and suggest that the EF network may mediate EM performance in this population.

// Jiu Chen 1 , Hao Shu 1 , Zan Wang 1 , Duan Liu 1 , Yongmei Shi 1 , Lin Xu 2 and Zhijun Zhang 1,3 1 Department of Neurology, Affiliated ZhongDa Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China 2 Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan, China 3 Department of Psychology, Xinxiang Medical University, Xinxiang, Henan, China Correspondence to: Zhijun Zhang, email: // Keywords : amnestic mild cognitive impairment, apolipoprotein E, entorhinal cortex, fMRI, functional connectivity, Gerotarget Received : May 05, 2016 Accepted : July 11, 2016 Published : August 14, 2016 Abstract The apolipoprotein E (APOE) e4 allele associates with accelerating the conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD), whereas the protectiveAPOEe2 allele appears to be against the disease. Moreover, entorhinal cortex (ERC) is one of the earliest brain regions of AD pathology that disrupts the formation of episodic memory. To investigate the effects of APOE e2 and e4alleles on functional connectivity (FC) of ERC and cognition in aMCI. Methods The FC analyses of ERC were performed in 83 aMCI (9 e2-carrier, 44 e3e3, and 30 e4-carrier) and 88 healthy controls (HC, 15 e2-carrier, 40 e3e3, and 33 e4-carrier). Multiple linear regression model was performed between the altered ERC connectivities and cognition. In the ERC network, aMCI with e4-carriers showed decreased FC in the bilateral middle temporal gyrus (MTG), right precuneus, and right precentral gyrus (PreCG), while e2-carriers showed increased FC in these regions (except the right PreCG) compared to HC. The altered FC between ERC and right MTG correlated with episodic memory performance in aMCI carried e2 and e4 alleles. These results suggest that the effects of APOE on the ERC network are closely linked to the role of this gene on AD risk, which aMCI with e4-carriers can accelerate the pathological progression of network-based mechanisms while e2-carriers may play a protective role in contributing to a compensatory mechanism. It further suggests that APOE can appear to directly affect the ERC-MTG neural pathway associated with the impairment of episodic memory in aMCI.

Sex estimation is an important part of creating a biological profile, and ultimately assisting in creating a presumptive identification of unidentified skeletal remains. However, manual methods of anthropometric are time-consuming and prone to observer variability. The present study is an attempt to estimation of sex from automatic measurement of patella by multidetector computed tomography (MDCT) in a contemporary Chinese population. Four measurements for every patella, including maximum height (MAXH), maximum breadth (MAXB), maximum thickness (MAXT) and patellar volume (PV), were automatically provided by the software from CT image of 300 Chinese. The sample is composed of 156 males and 144 females with an average age of 41.44 and 45.68 years, respectively. The statistical analyses showed that all variables were sexually dimorphic. Receiver operating characteristic (ROC) analysis was performed to estimate sex from patella. The univariate analysis of each patellar parameter yielded a sex classification accuracy rate of 73.1% to 85.7%. The classification accuracy rates of sex estimation using the combination of the patellar parameters are 81.9% to 91.6%. This paper provides indications that the patella is important bone for sex estimation and it may be used as an alternative in forensic cases when the skull and pelvis are unavailable.

Cognitive impairments have been reported in patients with pituitary adenomas (PAs). The aim of this research was to demonstrate the effects of hormones and age on cognitive decline in patients with PAs.A total of 64 patients with PA and 69 healthy control subjects (HCs) were recruited for this study. Both PAs and HCs were divided into a younger group (50 years of age) and an older group (≥50 years of age). Neurocognitive domains were assessed using the Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) tests. Furthermore, we also investigated the relationship between cognitive domains and tumor volume, and the hormone levels and age of patients with PA.Several of the cognitive impairments found on the WAIS-RC and WMS-RC tests were more frequently observed in untreated patients with PA. Importantly, no significant correlations were found between cognitive domains and tumor volume after controlling age, sex, and educational levels. Furthermore, several significant correlations were found between cognitive domains and hormone levels, such as free thyroxine and adrenocorticotropic hormone, after controlling age, sex, and educational levels. Finally, the age of the patients was found to correlate with a decrease in memory after controlling sex and educational levels.Our findings demonstrate a significant decline in the cognitive performance of patients with PA prior to medical treatment, especially in older patients, which suggests that hormones and age have the ability to interact and aggravate cognitive decline in patients with PA.

OBJECTIVE To explore the diagnostic value of carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) for the diagnosis of intrahepatic cholangiocarcinoma (ICC). STUDY DESIGN Case control study. PLACE AND DURATION OF STUDY First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to March 2018. METHODOLOGY Patients with ICC (n = 51) diagnosed by histological examination after surgery were matched 1:4 to control subjects (n = 204) based on age (±2 years), gender, and ethnicity. Serum CA 19-9 and CEA levels were determined and compared. Receiver operating characteristic (ROC) curves were generated, and areas under the receiver operating characteristic curve (AUC) were calculated. The cutoff values, sensitivities, specificities, and Youden index values were calculated and compared. RESULTS The levels of CA 19-9 and CEA were elevated in the ICC patients relative to control subjects (p

Background Fatty liver (FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics. Aim To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis. Methods Eight-week-old male C57BL/6 mice were divided into three groups randomly (control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin (HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids. Results Oil red O staining indicated lipid accumulation in the liver after CCl4 treatment. HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice on morphological examination. Hemorheological tests included whole blood viscosity (mPas, γ = 10 s-1/γ = 100 s-1) (8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ± 1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume (%) (51.00 ± 4.00, 42.00 ± 5.00, and 40.00 ± 3.00), the content of plasma fibrinase (g/L) (3.80 ± 0.50, 2.90 ± 0.80, and 2.30 ± 0.70), erythrocyte deformation index (%) (44.49 ± 5.81, 48.00 ± 15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate (mm/s per V/m) (0.55 ± 0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter (mL/min per 100 g) (94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope (μm/s) (325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02) revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller (μm) (10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79). Conclusion The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.

The purposes of this study are to investigate whether the Characterizing Alzheimer's disease Risk Events (CARE) index can accurately predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) on an individual subject basis, and to investigate whether this model can be generalized to an independent cohort. Using an event-based probabilistic model approach to integrate widely available biomarkers from behavioral data and brain structural and functional imaging, we calculated the CARE index. We then applied the CARE index to identify which MCI individuals from the ADNI dataset progressed to AD during a three-year follow-up period. Subsequently, the CARE index was generalized to the prediction of MCI individuals from an independent Nanjing Aging and Dementia Study (NADS) dataset during the same time period. The CARE index achieved high prediction performance with 80.4% accuracy, 75% sensitivity, 82% specificity, and 0.809 area under the receiver operating characteristic (ROC) curve (AUC) on MCI subjects from the ADNI dataset over three years, and a highly validated prediction performance with 87.5% accuracy, 81% sensitivity, 90% specificity, and 0.861 AUC on MCI subjects from the NADS dataset. In conclusion, the CARE index is highly accurate, sufficiently robust, and generalized for predicting which MCI individuals will develop AD over a three-year period. This suggests that the CARE index can be usefully applied to select individuals with MCI for clinical trials and to identify which individuals will convert from MCI to AD for administration of early disease-modifying treatment.

OBJECTIVE To explore the diagnostic accuracy of serum des-gamma-carboxy prothrombin (DCP) in adult primary cancer in liver. STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Department of Traditional Chinese Medicine, the First Affiliated Hospital, College of Medicine, Zhejing University, Hangzhou, China, from June 2016 to March 2018. METHODOLOGY A retrospective study of 1,190 cases was undertaken and all the participants were divided into Group 1 (non-cancer patients) and Group 2 (primary cancer in liver patients). The records of DCP and alpha fetoprotein (AFP) levels were extracted and compared between Group 1 and Group 2. The sensitivity, specificity, and cutoff point of DCP in Group 2 and its different histological types were calculated. The receiver operating characteristic (ROC) curves were obtained, and the areas under the receiver operating characteristic curve (AUROC) were calculated and compared in different histological types. RESULTS The DCP and AFP levels in Group 2 were markedly higher than Group 1 (p

Aim. To explore the diagnostic efficacy of des-gamma-carboxy prothrombin (DCP) in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). Methods. A retrospective study of 459 cases from June 2016 to March 2018 was undertaken, and records of the DCP levels were extracted. The sensitivity, specificity, and cutoff points were calculated using SPSS 17.0 software. A systematic search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials was performed for articles published in English from 1997 to 2017, focusing on serum DCP for HBV-related HCC. Data on sensitivity, specificity, the positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were extracted from five studies by systematic search and one study of our own. The summary receiver operating characteristic (sROC) curve was obtained, and the area under the receiver operating characteristic (AUROC) curve was calculated. Results. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.71 (95% CI: 0.59, 0.80), 0.93 (95% CI: 0.87, 0.96), 9.5 (95% CI: 5.2, 17.5), 0.32 (95% CI: 0.22, 0.46), and 30 (95% CI: 13, 72), respectively. The AUROC curve was 0.91 (95% CI: 0.88, 0.93). Conclusions. In the diagnosis of HBV-related hepatocellular carcinoma (HCC), DCP is an ideal marker that should be considered for surveillance purposes.

Background: The apolipoprotein E epsilon4 (ApoE ε4) allele and female gender may be important risk factors for the development of Alzheimer’s disease and amnestic mild cognitive impairment (aMCI). Novelty mismatch negativity (MMN) represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Furthermore, MMN and P3a components have been reported to be potential markers in aMCI. Therefore, this study will investigate the effects of gender and ApoE on auditory novelty MMN and P3a and their relationship to neuropsychological performance in aMCI. Methods: Thirty nine aMCI subjects and 44 controls underwent neuropsychological assessment and ApoE genotyping. Novelty MMN and P3a components were investigated during an auditory novelty oddball task. Results: Firstly, novelty MMN latency was significantly shorter in aMCI than in healthy control (HC) group. Secondly, novelty MMN latency was negatively correlated with episodic memory in aMCI, but not in HC. Novelty P3a latency was negatively correlated with information processing speed in all subjects. For gender effect, novelty MMN latency was shorter in aMCI females than in HC females. Moreover, novelty P3a amplitudes were lower in males than in females in both aMCI and HC. For the effect of ApoE status, novelty MMN latency was shorter in aMCI ApoE ε4- than HC ApoE ε4-. Conclusion: aMCI presents altered pre-attentive processing indexed by novelty MMN components. Furthermore, there may be a compensatory mechanism on the impaired processing in aMCI. It further suggests that aMCI female and ApoE ε4- recruited the compensatory mechanism.

Objective To quantify the low- to high-frequency range of abnormal brain activities and assess the histopathologic and clinical correlation in patients with glioma. Methods Twenty-five patients with glioma and 20 healthy controls were examined with a magnetoencephalography (MEG) system. MEG data collected in 6 frequency bands, including 1–4 Hz, 4–8 Hz, 8–12 Hz, 12–30 Hz, 30–45 Hz, and 55–75 Hz, were analyzed by neuropathology to assess neuromagnetic signatures of glioma grade. Results Compared with controls, patients with glioma showed greatly altered brain activities in 4–8 Hz, 8–12 Hz, and 55–75 Hz. Magnetic source power of brain activities in 4–8 Hz and 55–75 Hz in patients with high-grade gliomas significantly differed from that in patients with low-grade gliomas. The magnitude of source power of brain activities in 4–8 Hz and 55–75 Hz had marked correlation with the grading of gliomas in histopathological analyses. Conclusions The degree of neuromagnetic source abnormality is a potential biomarker for noninvasive assessment of glioma grade. Because MEG tests can be performed noninvasively and preoperatively, MEG may play an important role in clinical biopsies and surgical planning for patients with brain gliomas in the future.

Motor imagery is considered as an ideal window to observe neural processes of action representations. Behavioral evidence has indicated an alteration of motor imagery in amnestic mild cognitive impairment (aMCI). However, it still remains unclear on the altered neurophysiological processing mechanism of motor imagery and whether this mechanism links the abnormal biological basis of motor imagery with impaired cognition in aMCI. This study was to investigate the altered neurophysiological processing mechanism of motor imagery and to examine the relationships between this knowledge and the altered structural basis of motor imagery with impaired cognition in aMCI. A hand mental rotation paradigm was used to manipulate the processing of motor imagery while event-related brain potentials (ERPs) were recorded and gray matter (GM) voxel-based morphometry was performed in 20 aMCI and 29 healthy controls. Compared with controls, aMCI exhibited lower ERP amplitudes in parietal cortex and higher ERP amplitudes in frontal cortex during motor imagery. In addition, aMCI showed reduced GM volumes in cerebellum posterior lobe, insula and hippocampus/parahippocampal gyrus, and increased GM volumes in middle cingulate gyrus and superior frontal gyrus. Most importantly, increased ERP amplitude significantly mediated the association between increased GM and cognition. This study provided a novel evidence for the relationships between the electrophysiological processing mechanism and structural basis of motor imagery with impaired cognition in aMCI. It suggests that improving neural activity by stimulating the frontal lobe can potentially contribute to acquire motor imagery skills for neurological rehabilitation in aMCI subjects.

This study detected the differences in gene expression and DNA methylation of CpG sites in CXCL1 gene and further investigated their associations with clinical symptoms in deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). Pyrosequencing and RT-qPCR were separately used to determine DNA methylation and mRNA expression of CXCL1 gene. Both DNA methylation and expression were significantly different among DS, NDS and healthy control (HC) groups. Correlation analysis revealed that CXCL1 gene expression was associated with the negative syndrome in NDS patients, while no association in DS patients was observed. All together, these results suggest that DS may be a specific subgroup of schizophrenia with the characteristic abnormality of peripheral CXCL1 DNA methylation and gene expression.

OBJECTIVE To assess the necessity of prophylactic antibiotic therapy in HCC patients undergoing transcatheter arterial chemoembolization (TACE). STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY The First Affliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from August 2016 to August 2017. METHODOLOGY Retrospective TACE-treated cases were analysed in this study. The basic characteristics of the patients,the days in hospital, the laboratory data and fever after the procedure were assessed and compared. A review of literature of published studies and our present study were further conducted to determine the necessity of prophylactic antibiotic therapy. RESULTS In 159 cases, there were no significant difference in the leukocyte count (p=0.552), neutrophil count (p=0.573) and fever (p=0.31) with and without prophylactic antibiotic therapy groups. The hospital stay was significantly increased in the prophylactic antibiotic group (p

Background: Apolipoprotein E (APOE) ε4 is the only established risk gene for late-onset, sporadic Alzheimer’s disease (AD). Previous studies have provided inconsistent evidence for the effect of APOE ε4 status on the visuospatial working memory (VSWM). Objective: The aim was to investigate the effect of APOE ε4 on VSWM with an event-related potential (ERP) study in healthy controls (HC) and amnestic mild cognitive impairment (aMCI) patients. Methods: The study recorded 39 aMCI patients (27 APOE ε4 non-carriers and 12 APOE ε4 carriers) and their 43 matched controls (25 APOE ε4 non-carriers and 18 APOE ε4 carriers) with an 64-channel electroencephalogram. Participants performed an N-back task, a VSWM paradigm that manipulated the number of items to be stored in memory. Results: The present study detected reduced accuracy and delayed mean correct response time (RT) in aMCI patients compared to HC. P300, a positive component that peaks between 300 and 500 ms, was elicited by the VSWM task. In addition, aMCI patients showed decreased P300 amplitude at the central–parietal (CP1, CPz, and CP2) and parietal (P1, Pz, and P2) electrodes in 0- and 1-back task compared to HC. In both HC and aMCI patients, APOE ε4 carriers showed reduced P300 amplitude with respect to non-carriers, whereas no significant differences in accuracy or RT were detected between APOE ε4 carriers and non-carriers. Additionally, standardized low-resolution brain electromagnetic tomography analysis (s-LORETA) showed enhanced brain activation in the right parahippocampal gyrus (PHG) during P300 time range in APOE ε4 carriers with respect to non-carriers in aMCI patients. Conclusion: It demonstrated that P300 amplitude could predict VSWM deficits in aMCI patients and contribute to early detection of VSWM deficits in APOE ε4 carriers.

Introduction We investigated various favourable perceptions of ecigarettes (ECs) relative to cigarettes in adolescents and their associations with EC use intention among never EC users. Material and Methods In 2014/15, 40202 secondary 1-6 (US grade 7-12) students (51.5% boys, mean age 14.9±1.8 years) in Hong Kong were surveyed. The study factors were 13 perceived advantages of ECs over cigarettes (agree vs disagree). Intention to use ECs (outcome) referred to the lack of a firm decision not to use ECs in the next 12 months or when offered by a good friend. Weighted prevalence of the favourable perceptions of ECs in all students was calculated. Cox regression yielded prevalence ratios of intention to use ECs for each favourable perception in never EC users, excluding those unaware of ECs. Socio-demographic characteristics, cigarette smoking and school clustering effect were adjusted for. Results Of all students (n=40202), 47.2% perceived any advantages of ECs over cigarettes, with “less likely to cause accidents”, “less health harms on users” and “less health harms on others” being most common. In never EC users (n=24663), each favourable perception was associated with an intention to use ECs, the strongest were “more attractive”, “better accepted by parents” and “better accepted by schools”. Conclusions Favourable perceptions of ECs were strongly associated with intention to use ECs in adolescents who had never used ECs. Our findings support interventions to raise public awareness of the potential harms of ECs and increase parental and school disapproval of adolescent EC use, and effective regulations to prevent adolescent EC use. Funding The Food and Health Bureau, Hong Kong SAR Government, China

Introduction The present study aimed to investigate the negative perceptions of paternal and maternal smoking and their associated factors among adolescents in Hong Kong. Methods In a school-based cross-sectional survey in 2010 to 2011, 61,810 Hong Kong secondary school students (mean age 14.6 years, 50.8% boys) reported whether their parents smoked and whether they considered their parents’ smoking unacceptable and minded if their peers knew that their father or mother smoke (indicators of the negative perceptions). Factors associated with negative perceptions of paternal and maternal smoking were explored using multivariable regression models. Results Among students that reported paternal smoking (n=19.184, 29.8%), 50.8% considered it unacceptable, and 21.0% minded if their peers knew of it. Of those reporting maternal smoking (n=3,678, 5.7%), 48.1% considered it unacceptable, and 30.4% minded if their peers knew of it. Generally, the indicators of negative perceptions of parental smoking were associated with younger age, being certain about the harm of smoking and secondhand smoke, no peer smoking, and no secondhand smoke from the respective parent. Considering parental smoking unacceptable was additionally associated with lower family affluence and not living with any smokers apart from the respective parent. Conclusions About half of adolescents in Hong Kong with a smoking parent considered their parental smoking unacceptable, and about a quarter minded if their peers knew of their parent’s smoking. Such negative perceptions were more common in adolescents who were certain about the harm of tobacco, and had fewer co-residing smokers and no smoking peers.

Altered function of the medial temporal lobe (MTL) is a valuable indicator of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. This study is to delineate the functional circuitry of multiple subdivisions of parahippocampal gyrus and hippocampus (HIP) and to examine how this knowledge contributes to a more principled understanding of the contributions of its subregions to memory in aMCI. The functional connectivity (FC) analysis was performed in 85 aMCI and 129 healthy controls. The aMCI demonstrated the distinct disruptive patterns of the MTL subregional connectivity with the whole-brain. The right entorhinal cortex (ERC) and perirhinal cortex (PRC) showed increased connectivity with the left inferior and middle occipital gyrus, respectively, which potentially indicated a compensatory mechanism. Furthermore, the right altered MTL subregional FC was associated with episodic memory performance in aMCI. These results provide novel insights into the heterogeneous nature of its large-scale connectivity in MTL subregions in memory system underlying the memory deficits in aMCI. It further suggests that altered FC of MTL subregions is associated with the impairment of the differential encoding stages of memories and the functional changes in the specific right HIP-ERC-PRC-temporal circuitry may contribute to the impairment of episodic memory in aMCI.