Working memory impairment and reduced hippocampal and prefrontal cortex c-Fos expression in a rat model of cirrhosis

Hepatic encephalopathy (HE) is a frequent neurological complication observed in patients with liver malfunction. Previous studies have shown memory impairment in these patients. In order to investigate brain substrates of spatial working memory impairment in chronic HE, neuronal expression of c-Fos protein was studied in an experimental model of cirrhosis. Control and cirrhotic rats were trained on a spatial working memory task in the Morris water maze (MWM). Differences between groups were found in the working memory task. Cirrhotic rats were unable to locate the platform in the retention trial. Neuronal activation, measured by c-Fos protein, was compared between groups. No differences were found in c-Fos expression of control and cirrhotic rats that were not tested in the MWM. Working memory task produced increase in c-Fos positive cells in dorsal hippocampus, CA1 and CA3, and prefrontal cortex in control group compared to thioacetamide group or naïve, which only swam in the maze during a similar time. These findings suggest that cirrhotic rats show spatial working memory impairment that could be linked to dysfunction in neuronal activity in prefrontal cortex and hippocampus.     

成人回忆、再认和启动效应分离发展模式的研究

目的:考察成人(18～49岁)阶段不同的记忆功能发展变化的规律及其影响因素.方法:采用多维记忆评估量表中的6个分测验对280名正常成人进行记忆测查,并收集一般资料.结果:成人的自由回忆、再认记忆和启动效应成绩随年龄的增长均呈下降趋势,差异具有显著性(P<0.05),其中自由回忆和再认记忆减退比较明显,而启动效应减退相对缓慢;不同性别受试的记忆成绩随年龄变化的趋势基本一致;教育能对成人不同记忆功能的发展变化产生较为显著的影响.结论:成人阶段不同的记忆功能的发展并不是平行的,而是呈现一种分离发展的趋势.教育对成人记忆功能发展起到促进作用.     

脑外伤病人记忆功能的康复特点

脑外伤现已成为危害人们健康的主要疾病之一。脑外伤会引起多种认知功能障碍 ,如注意、记忆和语言等 ,其中记忆障碍较为常见。脑外伤后会有一段时间失去意识 ,同时伴有失定向、意识混乱 ,以及情节记忆受损等症状 ,称为创伤后遗忘 (ｐｏｓｔｔｒａｕ ｍａｔｉｃａｍｎｅｓｉａ ,ＰＴＡ) [1- 3] 。ＰＴＡ可以持续几分钟或几个月不等 ,它对于预测脑外伤后认知功能康复的程度等有重要的参考价值 ,ＰＴＡ的持续时间短 ,程度轻 ,其后认知功能的康复就会较好。对ＰＴＡ最简单的评价是询问病人在外伤后能够记起的第一件事 ,以及病人能够记起的外伤前…     

Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory

STUDY OBJECTIVE: To investigate which memory processes are affected by obstructive sleep apnea (OSA). DESIGN: Three separate memory systems were investigated in patients with OSA and normal subjects. Verbal episodic memory was tested after forced encoding, in order to control the level of attention during item presentation; procedural memory was tested using a simplified version of a standard test with an interfering task; lastly, working memory was examined with validated paradigms based on a theoretical model. SETTING: Sleep laboratory and outpatient sleep clinic in a French tertiary-care university hospital. PARTICIPANTS: Ninety-five patients with OSA and 95 control subjects matched for age and level of education. Group 1 (54 patients, 54 controls) underwent an extensive battery of tasks evaluating verbal episodic, procedural, and working memory. Group 2 (16 patients, 16 controls) underwent procedural memory tests only, and group 3 (25 patients, 25 controls) working memory tests only. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Compared with matched controls, patients with OSA exhibited a retrieval deficit of episodic memory but intact maintenance, recognition, and forgetfulness; decreased overall performance in procedural memory, although pattern learning did occur; and impairment of specific working memory capabilities despite normal short-term memory. No consistent correlation was found between OSA severity and memory deficit. The long duration of the test session did not negatively impact the patients' performance. CONCLUSIONS: Memory impairment in OSA is mild and does not affect all memory processes but, rather, specific aspects, underscoring the need for extensive and specific memory testing in clinical and research settings.     

Leukocyte arylsulfatase A activity in patients with alcohol‐related cirrhosis

Arylsulfatase (ASA) enzyme deficiency is associated with metachromatic leukodystrophy (MLD), which is a hereditary myelin metabolic disease. It has been proposed that in alcoholic subjects with abnormal ASA, the accumulation of sulfatides may lead to demyelinization and generalized cerebral atrophy. ASA may be diminished in subjects with alcoholic cirrhosis having encephalopathic manifestations. This idea has not been previously proposed. Leukocyte arylsulfatase A (ASA) activity was measured in 30 healthy male volunteers and 28 patients with alcohol‐related cirrhosis. The patients were divided into two groups: patients with alcohol‐related cirrhosis with hepatic encephalopathy history and patients with alcoholic cirrhosis without history of hepatic encephalopathy. Alcoholic cirrhotic patients with history of encephalopathy showed 58.21% (40.95 nmol/mg protein/h) less enzymatic activity than a control group (98.00 nmol/mg protein/h), whereas the group without history of encephalopathy showed an ASA value which was 38.2% (60.55 nmol/mg protein/h) less than the control group. The results suggest that the low ASA activity is a factor associated to the appearance of encephalopathy in patients with alcohol‐related cirrhosis. Am. J. Hum. Biol. 13:297–300, 2001. © 2001 Wiley‐Liss, Inc.     

成人数字、词语和视空间工作记忆广度的发展特征及影响因素

目的:考察成人(18~49岁)数字、词语和视空间工作记忆广度发展变化的趋势及其影响因素。方法:采用多维记忆评估量表中的3个工作记忆广度分测验对280名正常成人进行测查,并收集一般资料。结果:成人的数字、词语和视空间广度成绩随年龄的增长均呈下降趋势(F=2.96~6.87,P<0.01);出现随龄衰减现象的先后顺序依次为视空间广度、词语广度和数字广度;在记忆广度总成绩和大多数分测验成绩上男女无显著差异,仅在30-34岁年龄组,男性视空间广度位置的成绩好于女性(11.02±3.17/8.67±3.18,t=2.15,P<0.05)。逐步回归分析结果显示,教育是成人数字、词语和视空间广度的保护因素(Beta值=0.546,0.445,0.423;P<0.01)。结论:成人阶段数字、词语和视空间工作记忆广度的发展变化基本上趋于一致,并且受教育程度能对不同的工作记忆广度起促进作用。     

The ERP old-new effect: A useful indicator in studying the effects of sleep on memory retrieval processes

STUDY OBJECTIVES: To verify that the classic "Old/New" memory effect can be detected after a long delay, and to investigate the differential influence of declarative memory processes after normal sleep and daytime wake. DESIGN: The protocol is a variation of a more traditional study-recognition test used in event-related potential (ERP) studies in which sleep or wake is inserted between the learning and recognition session in order to verify the existence of the Old/New effect (ie, positive shift that occurs when stimuli are repeated). ERPs were recorded during the recognition-test session. The protocol was based on early work that compared the effect of sleep on memory without recording sleep. SETTING: Data collection occurred in the outpatient sleep laboratory. PATIENTS OR PARTICIPANTS: Results from 13 subjects (6 men) aged between 21 and 39 years. MEASUREMENTS AND RESULTS: The subjects performed the recognition memory test after sleep and daytime wake periods. More-accurate performance for the old (studied) stimuli occurred after the sleep session. Analysis of variance on correctly answered reaction times revealed a significant effect of condition (old/new) with no difference across session. A repeated-measure analysis revealed differences in "Old/New" effect, whereby the amplitude difference between the old and new items was larger after sleep than after wake. CONCLUSIONS: This effect of sleep was found in early frontal and later posterior ERP components, processes that represent strategic, contextual processing and facilitation of episodic memory. Memory representation was not different across sessions. These findings suggest that sleep and wake facilitate 2 components of memory unequally, ie, episodic recognition and memory representation functioning.     

能谱CT基物质分离技术在肝硬化与正常肝脏血流定量研究中的应用

目的:探讨能谱CT基物质分离技术在Child-Pugh A级肝硬化与正常肝脏血流动力学定量研究中的应用价值。方法:收集临床确诊肝硬化Child-Pugh A级并行上腹部增强CT检查患者30例作为肝硬化组,同时收集肝脏及门静脉增强CT检查无异常患者30例作为正常肝脏组。两组均采用能谱CT扫描并重建70 keV单能量图像、碘基物质分离图像,在70 keV、碘基图像上分别测量动脉期（AP）和门静脉期（PV）肝脏五叶（肝尾状叶、肝左外叶、肝左内叶、肝右前叶、肝右后叶）CT值和碘浓度（IC）,计算动脉期碘分数(AIF)和门静脉期碘含量（PVIC）。采用独立样本t检验比较两组能谱参数,并运用ROC曲线分析各参数诊断效能。结果:肝硬化组动脉期CT值和碘浓度与正常肝脏组无统计学差异（P>0.05）,而门静脉期CT值和碘浓度显著低于正常肝脏组（P<0.05）。肝硬化组肝脏AIF稍高于正常肝脏组（P>0.05）,而肝脏PVIC均显著低于正常肝脏组（P<0.05）。以门静脉期肝脏平均碘浓度21.47 mg/mL为阈值评价肝硬化与正常肝脏血流时,ROC曲线下面积（AUC）为0.790,敏感度为77.8%,特异度为83.3%,显著高于肝脏CT值和PVIC。结论:能谱CT基物质分离技术可以用来评价肝硬化与正常肝脏血流动力学的改变和差异,为肝硬化的早期诊断提供更多依据。     

Emotion-induced memory dysfunction in borderline personality disorder

Introduction. Although emotional dysregulation is a core problem in borderline personality disorder (BPD), few neuropsychological studies have evaluated the impact of emotion. The present study aimed at the comprehensive investigation of verbal memory functions with and without emotionally relevant interference in BPD. BPD patients were expected to perform as well as healthy subjects in standard memory tasks but to show fewer capacities to control for emotionally negative interference.

Methods. 47 patients with BPD and 70 healthy control subjects participated. An experimental task assessed verbal memory with respect to standard and emotionally relevant and neutral interference learning conditions. Applied standard tests covered working memory, delayed memory, and word fluency.

Results. Memory performances of BPD patients were impaired when negatively valenced interference was conducted but normal in all other conditions. These results remained stable after controlling for comorbid major depression and posttraumatic stress disorder.

Discussion. The present findings suggest no general impairment of verbal memory functions in BPD but control and inhibition of interference by emotionally significant material seem to be disturbed.     

N-terminal pro B-type natriuretic peptide and the evaluation of cardiac dysfunction and severity of disease in cirrhotic patients

PURPOSE: Cardiac dysfunction and hyperdynamic systemic circulation may be present in patients with cirrhosis. The purpose of this study was to identify relations between plasma levels of N-terminal-proBNP (NT-proBNP), reflecting early ventricular dysfunction, and the severity of liver disease and cardiac dysfunction in cirrhotic patients. MATERIALS AND METHODS: Sixty-three cirrhotic patients and 15 controls (group 1) were enrolled in this study. Plasma levels of NT-proBNP were determined in echocardiographically examined patients, which were allocated to 1 of 3 groups according to Child-Pugh classification or into 2 groups, i.e., a compensated group without ascites (group 2) and decompensated group with ascites (group 3). RESULTS: Plasma NT-proBNP levels were significantly higher in cirrhotic patients (groups 2 and 3) than in age-matched controls (155.9 and 198.3 vs. 40.3 pg/mL, respectively, p < 0.05). NT-proBNP levels were significantly increased in Child class C patients than in classes B and A (250.0 vs. 168.6 and 119.6 pg/mL, respectively, p < 0.05). Left atrial dimension, wall thickness of left ventricle, and EF or E/E' were significantly increased, and EDT was prolonged in cirrhotic patients than in controls. Increased LVMI and decreased E/A ratio were noted in the group of patients with ascites as compared with the other groups. CONCLUSION: Plasma NT-proBNP levels were high in cirrhotic patients and are likely to be related to the severity of disease. Advanced cirrhosis is associated with advanced cardiac dysfunction, and NT-proBNP levels has predictive value for concomitant cardiac dysfunction and cirrhosis progression.     

PSA-NCAM expression in the rat medial prefrontal cortex

Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from cirrhotic patients. The aim of this work was to assess whether an animal model of cirrhosis, bile duct ligation, alone or combined with diet-induced hyperammonemia for 7-10 days reproduces the alterations in NO modulation of sGC found in brains from cirrhotic patients. sGC activity was measured under basal conditions and in the presence of NO in cerebellum and cerebral cortex of the following groups of rats: controls, bile duct ligation without or with hyperammonemia and hyperammonemia without bile duct ligation. In cerebellum activation of sGC by NO was significantly lower in bile duct ligated rats with (12 +/- five-fold) or without (14 +/- six-fold) hyperammonemia than in control rats (23 +/- seven-fold). In cerebral cortex activation of sGC by NO was higher in rats with bile duct ligation with hyperammonemia (124 +/- 30-fold) but not without hyperammonemia (59 +/- 15-fold) than in control rats (66 +/- 11-fold). The combination of bile duct ligation and hyperammonemia reproduces the alterations in the modulation of soluble guanylate cyclase by NO found in cerebral cortex and cerebellum of cirrhotic patients while bile duct ligation or hyperammonemia alone reproduces the effects in cerebellum but not in cerebral cortex.     

肝炎肝硬化患者外周血自然杀伤细胞的变化与HLA-Cw基因型相关性研究

目的 研究乙型肝炎病毒(HBV)引起的肝炎肝硬化和急性乙型肝炎患者外周血自然杀伤细胞(NK)和活化NK细胞数量的变化及其与HLA-Cw基因型的关系.方法 选择肝炎肝硬化和急性乙型肝炎发病期患者各30例及健康对照者41例,采用流式细胞仪检测外周血NK细胞和活化NK细胞的数量,并通过PCR-SSO(polymerase chain reaction-sequence specific oligonucleotide)的方法进行HLA-Cw的基因分型.结果 肝炎肝硬化组NK细胞和活化NK细胞的数量分别是13.22%±4.61%和45.68%±14.64%,均低于健康对照组(P<0.05),急性乙型肝炎组NK细胞和活化NK细胞的数量分别是22.62%±3.70%和65.28%±14.45%,均较健康对照组增高(P<0.05),且肝炎肝硬化组与急性乙型肝炎组比较差异有统计学意义(P<0.01);HLA-Cw*15在肝炎肝硬化组中基因频率明显高于健康对照组(P<0.05),且与活化NK细胞数量呈显著负相关(r=-0.862,P<0.05),急性乙型肝炎组与健康对照组间HLA-Cw位点各等位基因的基因型差异无统计学意义(P>0.05).结论 肝炎肝硬化患者NK细胞功能低下,HLA-Cw*15基因型可能是通过影响NK细胞而导致HBV感染持续存在的原因之一.     

Impaired memory consolidation during sleep in patients with functional memory disorder

Functional memory disorder (FMD) is characterized by mnestic and attentional deficits without symptoms of mild cognitive impairment or dementia. FMD usually develops in subjects with high psychosocial stress level and is classified to the somatoform disorders. We assessed memory performance (procedural mirror tracing task, declarative visual and verbal memory task) and other cognitive functions before and after one night of sleep in 12 FMD patients (mean age: 51.7 yrs, 7 females) and 12 healthy subjects matched for age, gender and IQ. Memory performance and other neurocognitive tasks did not differ between the groups at baseline. After one night of sleep, FMD patients showed an impairment of declarative memory consolidation compared to healthy subjects (visual task: p = 0.004; verbal task: p = 0.039). Spectral analysis of sleep-EEG indicated an increased cortical excitation in FMD. We hypothesize that a hyperarousal state in FMD might contribute to sleep disturbance implicating negative effects on declarative memory consolidation.     

Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.     

Variability in memory performance in aged healthy individuals: an fMRI study

Episodic memory performance varies in older subjects but underlying biological correlates remain as yet ambiguous. We investigated episodic memory in healthy older individuals (n=24; mean age: 64.4+/-6.7 years) without subjective memory complaints or objective cognitive impairment. Episodic memory was assessed with repetitive learning and recall of abstract geometric patterns during fMRI. Group analysis of brain activity during initial learning and maximum recall revealed hippocampal activation. Correlation analysis of brain activation and task performance demonstrated significant hippocampal activity during initial learning and maximum recall in a success-dependent manner. Neither age nor gray matter densities correlated with hippocampal activation. Functional imaging of episodic memory thus permits to detect objectively variability in hippocampal recruitment in healthy aged individuals without subjective memory complaints. Correlation analysis of brain activation and performance during an episodic memory task may be used to determine and follow-up hippocampal malfunction in a very sensitive manner.     

31P and 1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats.

NMR spectroscopy was used to examine hepatic metabolism in cirrhosis with a particular focus on markers of functional cellular hypoxia. (31)P and (1)H NMR spectra were obtained from liver extracts from control rats and from rats with carbon tetrachloride-induced cirrhosis. A decrease of 34% in total phosphorus content was observed in cirrhotic rats, parallelling a reduction of 40% in hepatocyte mass as determined by morphometric analysis. Hypoxia appeared to be present in cirrhotic rats, as evidenced by increased inorganic phosphate levels, decreased ATP levels, decreased ATP:ADP ratios (1.72 +/- 0.40 vs 2.48 +/- 0.50, p < 0.01), and increased inorganic phosphate:ATP ratios (2.77 +/- 0.48 vs 1.62 +/- 0.24, p < 0.00001). When expressed as a percentage of the total phosphorus content, higher levels of phosphoethanolamine and lower levels of NAD and glycerophosphoethanolamine were detected in cirrhotic rats. Cirrhotic rats also had increased phosphomonoester:phosphodiester ratios (5.73 +/- 2.88 vs 2.53 +/- 0.52, p < 0.01). These findings are indicative of extensive changes in cellular metabolism in the cirrhotic liver, with many findings attributable to the presence of intracellular hypoxia.     

Effects of sleep restriction on cognition in women

The aim of the present study was to investigate how three nights of sleep restriction affected cognitive functions in young and aged healthy women. Ten young (20-30 years) and ten aged (55-65 years) women participated to the study. After one baseline night (11 pm-07 am), their sleep was restricted to 4h per night (01-05 am) during three nights. A recovery night of 8h (11 pm-07 am) followed the sleep restriction. The neurobehavioural assessment included evaluation of Attention (Stroop, Trail Making test, Tests of Attentional Performance), Memory (Buschke, Logical Memory, PASAT, Brown Peterson), Addition of numbers and Abstraction (Wisconsin). Sleep restriction decreased significantly the speed of execution, particularly in the young women, without affecting the accuracy of the answers. This effect was the most significant on reaction times in simple tests. The more complex tasks (PASAT, Brown Peterson, Logical Memory, Addition of numbers, Wisconsin) were not affected. However, the inhibition of an automatic activity (Stroop test) and the formation of a memory trace (Buschke memory test) were disturbed in both young and older women.     

Immune parameters in a population of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations.

Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence.     

老年无症状性脑梗死患者记忆功能的研究

目的 :探讨老年无症状性脑梗死 (ACI)与记忆障碍的关系。方法 :对 5 0例ACI患者进行了临床记忆量表检测 ,同时用韦氏成人智力量表对ACI组进行智力测查。结果 :ACI组各项记忆成绩及MQ均明显低于正常对照组 (P <0 0 1) ,但与症状性脑梗死组 (SCI)比较无差异 ;不同梗死区域有其记忆损伤的特点 ;ACI组中智力障碍者 13例 (2 6% )。MQ在 80以上者均智力正常。结论 :老年ACI存在明显记忆障碍     

Correlation between different memory systems and striatal dopamine D2/D3 receptor density: a single photon emission computed tomography study

OBJECTIVE: Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals. METHOD: Single photon emission computed tomography and [123I]IBZM (iodobenzamide) were used to assess the striatal dopamine D2/D3 receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale-Revised test. RESULTS: Dopamine D2/D3 receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D2/D3 measurements. These relationships remain significantly after controlling for age effects. CONCLUSIONS: Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments.