Analysis of long range dependence in the EEG signals of Alzheimer patients

Alzheimer’s disease (AD), a cognitive disability is analysed using a long range dependence parameter, hurst exponent (HE), calculated based on the time domain analysis of the measured electrical activity of brain. The electroencephalogram (EEG) signals of controls and mild cognitive impairment (MCI)-AD patients are evaluated under normal resting and mental arithmetic conditions. Simultaneous low pass filtering and total variation denoising algorithm is employed for preprocessing. Larger values of HE observed in the right hemisphere of the brain for AD patients indicated a decrease in irregularity of the EEG signal under cognitive task conditions. Correlations between HE and the neuropsychological indices are analysed using bivariate correlation analysis. The observed reduction in the values of Auto mutual information and cross mutual information in the local antero-frontal and distant regions in the brain hemisphere indicates the loss of information transmission in MCI-AD patients.     

Cognitive impairments in abstinent alcoholics.

Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person''s age. Surprisingly, the pattern and duration of a patient''s alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism.     

Neuropsychological profile in a large group of heart transplant candidates

Background

Recent studies have reported that patients with end-stage heart disease can have cognitive deficits ranging from mild to severe. Little is known, however, about the relationship between cognitive performance, neurophysiological characteristics and relevant clinical and instrumental indexes for an extensive evaluation of patients with heart failure, such as: left ventricular ejection fraction (LVEF) and other haemodynamic measures, maximum oxygen uptake during cardiopulmonary exercise testing, comorbidities, major cardiovascular risk factors and disease duration. Our purpose was to outline the cognitive profiles of end-stage heart disease patients in order to identify the cognitive deficits that could compromise the quality of life and the therapeutic adherence in end-stage heart disease patients, and to identify the variables associated with an increased risk of cognitive deficits in these patients.

Methods

207 patients with end-stage cardiac disease, candidates for heart transplant, were assessed by complete neuropsychological evaluation and by electroencephalographic recording with EEG spectral analysis.

Results

Pathological scores in one or more of the cognitive tests were obtained by 86% of the patients, while 36% performed within the impaired range on five or more tests, indicating poor performance across a broad range of cognitive domains. The executive functions were the cognitive domain most impaired (70%). Poor performances were not related to the aetiology of heart disease, but rather to cerebral dysfunction secondary to haemodynamic impairment and to comorbidities.

Conclusions

Severe heart failure induces significant neurophysiological and neuropsychological alterations, which may produce an impairment of cognitive functioning and possibly compromise the quality of life of patients and the therapeutic adherence.     

Pattern of neuropsychological performance among HIV positive patients in Uganda

Background  

Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda.     

老年认知障碍常用神经心理测验的应用进展

随着医学进步,人类平均寿命不断延长,人口老龄化问题越来越突出,老年认知障碍患者不断增加。而神经心理测验在不同程度认知功能损害的诊断中的作用已日益引起重视。就认知功能损害诊断常用的神经心理测验进行综述,为临床认知功能检查提供依据。     

Artificial and Bioartificial Liver Support

The liver is a complex organ with various vital functions in synthesis, detoxification and regulation; its failure therefore constitutes a life threatening condition1. Liver failure (LF) can either occur without preceding liver disease (acute liver failure, ALF), usually caused either by intoxication (Amanita phalloides, acetaminophen, methylendioxymethamphteamine) or as acute decompensation of chronic liver-related illness (acute-on-chronic liver failure, AoCLF). In both cases, its symptoms include icterus, hepatic encephalopathy and impairment of coagulation status and may result in multi organ failure. Exceptionally, liver failure may also be triggered by certain diseases (Budd-Chiari-syndrome, Morbus Wilson) or pregnancy. The only long-term therapy in most cases is orthotopic liver transplantation, unless the liver is able to regenerate. Many patients, especially those who are not listed for high urgency transplantation, may not survive until a suitable donor organ is available, since donor organs are rare. In other cases, contraindications do not permit liver transplantation. For these indications, extracorporeal liver assist devices have been developed in order to either bridge the patient to transplantation or temporarily support the failing organ until it is able to regenerate.     

The impact of the 1991 Gulf War on the mind and brain: findings from neuropsychological and neuroimaging research

Many veterans of the 1991 Gulf War (GW) have complained of somatic and cognitive symptoms that may be neurological in nature. However, whether or not changes in brain function are associated with GW service continues to be debated. Studies of GW veterans using objective, performance-based neuropsychological measures have yielded inconsistent findings, with those indicating deficits among GW veterans typically revealing only relatively mild levels of neuropsychological impairment. Further, performances on objective neuropsychological tasks show little correspondence to subjective perceptions of cognitive functioning. Although preliminary magnetic resonance spectroscopy (MRS) studies demonstrate reduced N-acetylaspartate-to-creatine (NAA/Cr) ratio in select brain regions among GW veterans who report health concerns, this work requires further replication with larger, more representative samples. There is no evidence from neuroimaging studies of a non-specific effect of GW service or of changes in brain structure or function related to health status when conventional radiological methods are used. Owing to the paucity of objective exposure, baseline health data, and the now significant time elapsed since the GW, aetiological issues may never be fully resolved. Therefore, research addressing clinical management of GW veterans with neuropsychological dysfunction and neuroimaging abnormalities may prove more fruitful than exclusive focus on aetiology.     

Cognitive Functioning in Clinically Stable Patients with Bipolar Disorder I and II

Objectives

Bipolar disorder is accompanied by cognitive impairments, which persists during euthymic phases. The purpose of the present study was to identify those neuropsychological tests that most reliably tell euthymic bipolar patients and controls apart, and to clarify the extent to which these cognitive impairments are clinically significant as judged from neuropsychological norms.

Methods

Patients with bipolar disorder (type I: n = 64; type II: n = 44) and controls (n = 86) were examined with a comprehensive neuropsychological test battery yielding 47 measures of executive functioning, speed, memory, and verbal skills. Multivariate analysis was used to build a model of cognitive performance with the ability to expose underlying trends in data and to reveal cognitive differences between patients and controls.

Results

Patients with bipolar disorder and controls were partially separated by one predictive component of cognitive performance. Additionally, the relative relevance of each cognitive measure for such separation was decided. Cognitive tests measuring set shifting, inhibition, fluency, and searching (e.g., Trail Making Test, Color-Word) had strongest discriminating ability and most reliably detected cognitive impairments in the patient group.

Conclusions

Both bipolar disorder type I and type II were associated with cognitive impairment that for a sizeable minority is significant in a clinical neuropsychological sense. We demonstrate a combination of neuropsychological tests that reliably detect cognitive impairment in bipolar disorder.     

Evidence for cognitive impairment in mastocytosis: prevalence, features and correlations to depression

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n?=?57; mean age?=?45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n?=?22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.     

Selenium and cognitive impairment: a brief-review based on results from the EVA study

Preventing cognitive impairment and dementia in the elderly is a major public health challenge for our century and all hypotheses should be explored. Selenium (Se) is one of the factors that may affect the risk of cognitive decline. Its importance in the health and aging process has been documented. Because of the potential of selenoproteins to protect against oxidative stress, Se raises significant expectations for the prevention of chronic diseases including cancer, cardiovascular disease, and type 2 diabetes conditions commonly associated with oxidative stress. Thus, the relationships between Se and cognitive impairment or dementia can be examined through vascular risk factors for dementia, with particular interest in diabetes and dyslipidemia. In addition, in cases of Se deficiency, the brain is the organ that remains Se replete the longest suggesting that Se plays an important role in brain functions. This article presents results obtained in the frame of a longitudinal study on Se and cognitive impairment. They are consistent with the hypothesis that low Se status is a risk factor for cognitive decline even after taking into account vascular risk factors. The concomitant evolution between plasma Se decrease over a 9-year period and cognitive decline suggested that optimal Se status is potentially important to maintain neuropsychological functions in aging people. However, as our understanding of Se biology is incomplete, epidemiological studies are needed to define the groups of population that could benefit from Se supplementation.     

Cognitive dysfunction in rapid eye movement sleep behavior disorder

Cognitive impairment is a frequent feature of rapid eye movement sleep behavior disorder (RBD). The cognitive profile of RBD patients is heterogeneous, with impairments in attention, executive functions, episodic memory, and visuospatial abilities. Moreover, over 50% of RBD patients meet the diagnostic criteria for mild cognitive impairment (MCI). Although a comprehensive neuropsychological assessment remains the most sensitive way to detect MCI, three cognitive screening tests have been validated in RBD. The Montreal Cognitive Assessment was found to be the most appropriate screening test for detecting MCI in RBD. In addition RBD in Parkinson’s disease may be a risk factor for MCI and dementia.

     

Gray Matter Correlates of Cognitive Performance Differ between Relapsing-Remitting and Primary-Progressive Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS). Most patients experience a relapsing-remitting (RR) course, while about 15–20% of patients experience a primary progressive (PP) course. Cognitive impairment affects approximately 40–70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS) and thirty-eight matched controls underwent neuropsychological (NP) testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course.     

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD.     

Inflammatory Cascades Driven by Tumor Necrosis Factor-Alpha Play a Major Role in the Progression of Acute Liver Failure and Its Neurological Complications

Background/aims

Acute liver failure (ALF) due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE), a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α) in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity.

Methods/Principal Findings

Mice were administered saline or etanercept (10 mg/kg; i.p.) 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001) and CD40L levels (3.7-fold; p<0.001) compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05), attenuated microglial activation (assessed by OX-42 immunoreactivity), and increased brain glutathione concentrations.

Conclusions

These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.     

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed.     

Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1

The objective of this study was to ascertain the impact of aging and Alzheimer's disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment ( n  = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography–mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work.     

Linkage of gut microbiome with cognition in hepatic encephalopathy

Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE (n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae, Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae) compared with controls. We found altered flora (higher Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.     

综述:轻度认知障碍的神经心理损伤特征及其早期识别与干预——预防和延缓阿尔茨海默病的发生

轻度认知障碍(mild cognitive impairment,MCI)是介于正常老化和痴呆之间的过渡阶段,MCI患者是阿尔茨海默病(Alzheimer's disease,AD)的风险人群．本文介绍了国际上MCI诊断标准及其变化和修订,提出了理想的诊断模型．根据国内外研究,从认知和精神行为两个方面综述了MCI的神经心理损伤特征及其相应的诊断工具,简要回顾了现有针对MCI开展干预的各种方法．指出早期识别和干预研究需要从实验室小样本扩展到社区大样本老年人群,从横断研究扩展到纵向追踪,综合采用多种识别指标,并结合多种干预方法以达到最优效果．     

Neural Substrates of Cognitive Subtypes in Parkinson's Disease: A 3-Year Longitudinal Study

Background

The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinson''s disease (PD) remain to be elucidated.

Methods

Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography.

Results

Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease.

Conclusions

These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.