Behavioral and cognitive effects of the N-methyl-d-aspartate receptor co-agonist d-serine in healthy humans: Initial findings

The efficacy of compounds having agonistic activity at the glycine site associated with the N-methyl-d-aspartate receptor (NMDAR) is presently assessed in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric effects of NMDAR agonists in the healthy human organism are not known. We studied neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory co-agonist d-serine (DSR) in healthy subjects using a randomized, controlled crossover challenge design including a baseline assessment day and two DSR/placebo administration days. Thirty-five subjects aged 23–29 years participated in the study and received a 2.1 g orally administered DSR dose. The main outcome measures were the changes in scores of mood-related Visual Analogue Scale (VAS), Continuous Performance Test–Identical Pairs (CPT-IP), and Rey Auditory Verbal Learning Test (RAVLT). DSR acute administration: (1) was well tolerated and resulted at 2 h in ≥200 times increase in DSR serum levels; (2) elicited reduced VAS-measured depression and anxiety feelings; (3) improved attention and vigilance as measured by CPT-IP d-prime score; (4) preferentially improved performance in RAVLT list 7 reflecting ability to retain information over interference; (5) had significant but nonspecific effects on Category Fluency and Benton Visual Retention tests; and (6) did not affect glycine and glutamate serum levels. These data indicate that in healthy subjects, DSR reduces subjective feelings of sadness and anxiety and has procognitive effects that are overall opposed to the known effects of NMDAR antagonists. The findings are relevant to translational research of NMDAR function and the development of NMDAR-glycine site treatments for specific psychiatric entities.ClinicalTrials.gov: Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans; http://www.clinicaltrials.gov/ct2/show/NCT02051426?term=NCT02051426&rank=1; NCT02051426.     

海洛因依赖者认知功能损害的对照研究

目的　采用威斯康星 (Wisconsin)卡片分类测验评估海洛因依赖者与正常人群的认知差异。方法　对完成脱瘾治疗的 4 8例海洛因依赖者和 4 2例正常人进行Wisconsin卡片分类测验评定。结果　两组间总应答数、完成分类数、正确应答百分数、错误应答数、持续应答数、持续性错误数、概念化应答百分数和完成第一类所需应答数的比较显示 ,海洛因依赖组较正常人组差 (P <0 0 1)。相关因素分析显示 ,吸毒时间及日吸毒量与认知功能损害程度呈正相关 (r分别为 0 4 1～ 0 4 7和 0 35～ 0 4 2 ;P <0 0 5 )。结论　海洛因依赖者存在认知功能损害     

比较内外科治疗少量高血压性丘脑出血对认知功能的影响

目的:比较内科保守治疗与外科钻孔引流对少量(20-30ml)高血压性丘脑出血患者认知功能的影响。方法:选择较少量高血压性丘脑出血病例60例,随机分为内科保守治疗和外科钻孔引流治疗各30例。运用简易精神状态量表(mini mental state examination,MMSE)评价治疗前和治疗后1个月及3个月病人的认知状态。结果:外科钻孔引流治疗组MMSE分值增加明显高于内科治疗组,具有统计学意义。结论:外科钻孔引流治疗对较少量高血压性丘脑出血患者认知功能的恢复更有意义。     

蒙特利尔认知评估量表在乌鲁木齐维吾尔族人群中应用的初步研究

目的 对维吾尔文版蒙特利尔认知评估量表( MoCA-U)在乌鲁木齐地区维吾尔族人群中应用的信度及效度进行检验,并初步确定该量表筛查维吾尔族认知障碍人群的最佳界值.方法 对英文版MoCA量表进行翻译并修订成维吾尔文版,选择188名50～75岁的维吾尔族研究对象,其中正常对照组80名、轻度认知功能障碍(MCI)组68例、痴呆组40例,分别用MoCA-U、简易精神状态量表(MMSE)、临床痴呆量表(CDR)等神经心理学量表进行评估比较.结果 (1)MoCA-U的克朗巴赫α系数为0.801,评定者间一致性组内相关系数为=0.977(95％可信区间;0.949～0.990),重测信度r =0.987(P ＜0.001).(2)正常对照组、MCI组、痴呆组的MoCA-U总分分别为(22.65±2.57)、(18.56±3.08)、(9.43±3.89)分,3组比较差异有统计学意义(F=27.991,P＜0.001);MoCA-U与MMSE、CDR量表总分的相关系数分别为r=0.84(P ＜0.001)和r=-0.77(P ＜0.001).(3)当研究对象受教育年限≤5年时,MoCA-U筛查MCI的最佳界值为20分,此时MoCA-U灵敏度为86.4％,特异度为84.2％;筛查痴呆的最佳界值为13分,此时的灵敏度为94.1％、特异度为100％.受教育年限6～10年时,MoCA-U筛查MCI的最佳界值为21分,灵敏度为84.6％,特异度为94.1％;筛查痴呆的最佳界值为15分,此时的灵敏度为100％,特异度为92.3％.受教育年限≥11年时,MoCA-U筛查MCI的最佳界值为22分,灵敏度为75.8％,特异度为70.5％;筛查痴呆的最佳界值为17分,此时的灵敏度为100％,特异度为84.8％.结论 MoCA-U具有良好的信效度及可行性,适合对乌鲁木齐中老年维吾尔族人群认知功能进行评估;不同受教育程度人群筛查MCI的最佳界值为20～22分,筛查痴呆的最佳界值为13～17分.     

轻度认知功能障碍的神经心理学研究

轻度认知功能障碍（Mlid cognitive imairment,MCI）是近年来提出的新概念,是一种介于正常老化的认知改变和阿尔茨海默病（Alzheimer＇s Disease,AD）之间的中间状态,是目前人们关注的焦点问题.     

Cognitive triggers of auditory hallucinations: An experimental investigation

It has proved difficult to establish the internal process by which mental events are transformed into auditory hallucinations. The earlier stages of the generation of hallucinations may prove more accessible to research. Cognitions have been reported by patients as a trigger of auditory hallucinations, but the role of these preceding thoughts has not been causally determined. Therefore, the role of cognition in triggering auditory hallucinations was tested in an experimental study. Thirty individuals who experienced auditory hallucinations in social situations entered a neutral social situation presented using virtual reality. Participants randomised to the experimental condition were instructed to think their hallucination-preceding thoughts, and those randomised to the control condition were instructed to think neutral thoughts. Twenty-seven participants (93%) were able to spontaneously identify a cognition which preceded a hallucination. There was no difference between the experimental and control groups in the occurrence or severity of auditory hallucinations in virtual reality. Virtual reality did not lead to physical side effects or an increase in anxiety. The relationship between antecedent cognitions and auditory hallucinations is likely to be more complex than the one tested. It is argued that the effect of cognition on auditory hallucinations may be mediated by affect but this needs to be investigated through further experimental research.     

Neuropsychological deficits in patients with Sneddon's syndrome

The results of a neurological, neuropsychological and MRI study of the brain in 21 patients (aged 18–59 years) with Sneddon's syndrome are reported. The predominant findings were marked neuropsychological deficits in two-thirds of the patients. While sensorimptor deficits after stroke in these patients had a good prognosis, neuropsychological deficits persisted. Of the 21 patients, 14 were incapable of gainful employment, 10 because of severe cognitive dysfunction.     

失语症患者口语命名障碍中语义错误的原因初探

目的从认知神经心理学的角度分析失语症患者口语命名障碍中语义错误的不同机制。方法对2例口语中语义错误的汉语失语症患者，分别通过口语图形命名、图形写名、词／图匹配及图／词核证等测验，检查他们各项任务的正确率及错误模式，分析各自的损伤环节。结果2例患者在口语图形命名任务中正确率相当，并都犯有大量的语义错误，但在几项理解任务中，例1基本正常，而例2的成绩显著偏低。2例所犯的错误性质有所不同。结论口语图形命名障碍中的语义错误源于不同的损伤环节：例1主要为语义后的输出系统受损，而例2则为中心语义系统受损。     

糖耐量损害大鼠脑组织NF-κBp65及TNF-α表达水平与认知障碍的关系

目的研究大鼠脑组织NF-κBp65,TNF-α因子在认知障碍中的作用,从炎症角度探讨糖耐量损害对认知障碍的影响。方法高脂高糖饲养法建立糖耐量损害大鼠模型;水迷宫法检测大鼠认知功能;免疫组化法检测NF-κBp65,TNF-a表达水平。结果实验组学习记忆能力在第5周较对照组高（P〈0.05）,第10、15、20周逐次下降,且低于相同时间点对照组（P〈0.05）。Pearson相关分析显示NF-κBp65,TNF-α阳性表达水平与大鼠认知障碍呈正相关（r=0.972,r=0.975,P〈0.05）。结论糖耐量损害与大鼠认知障碍有关,炎症机制可能是其重要机制之一。     

不同年龄脑卒中和非卒中者事件相关电位P300研究

目的检测不同年龄脑卒中患者和非卒中查体者事件相关电位P300的变化,观察认知功能的改变.方法脑卒中(卒中组)36例,非卒中者(对照组)56例,分三个年龄段(36～50岁、51～60岁、61～70岁),其中卒中者又按病程分为急性发病后＜2周,2周～6月,＞6月等观察.P300检查采用NDI-500神经电检测仪.计算机显示结果后打印记录.结果(1)卒中组与对照组比较P300潜伏期明显延长(p＜0.001),波幅显著变小(p＜0.001);(2)不同年龄段二组相比P300潜伏期明显延长,波幅显著减少.且对照组中年龄61～70岁组其P300潜伏期比36～50岁组明显延长;(3)卒中病程＞6月组P300潜伏期与＜2周组相比明显延长(p＜0.05),波幅明显减少(p＜0.05);(4)小病灶者P300潜伏期与大病灶者相比无明显差别(p＞0.05).结论年龄是影响学习记忆的一个重要因素,随年龄增高,认知功能下降.脑卒中病人存在明显认知障碍.卒中病程越长患者认知功能越差.     

城市老年人认知功能及影响因素的调查分析

目的　调查城市老年人认知功能问题及影响因素 ,提出保健需求。方法　采取分层抽样方法对山东省 8个城市 6 5岁以上老人 ,以简明精神状态检查 (MMSE)、韦氏成人智力量表 (WAIS)中的数字广度测验(DST)得分进行认知功能评定及相关因素调查。对所获资料进行t检验、方差分析、非条件Logistic回归分析。结果　共取样 2 4 85名老人 ,其MMSE得分男性高于女性 (2 5 6± 5 2 / 2 2 0± 6 4 ,t=15 4 ,P <0 0 1)。影响老年人认知功能的危险因素有 :高龄、文盲、农民或无正式职业、日常生活能力、社会支持、焦虑、抑郁等。结论　影响老年人认知功能的因素很多 ,有针对性地加强保健措施是必要的     

Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: A clinical and MRI pilot-study

Background

Studies providing information about the cognitive profile of adult haemophiliacs are lacking.

Aims

To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings.

Methods

Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) “Short Neuropsychological Test” assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma.

Results

49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p = 0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R = − 0.32 p < 0.05). CMBs were associated with cardiovascular risk factors (p = 0.018).

Conclusions

Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn’t correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.     

The challenge of time: Clock-drawing and cognitive function in the elderly

This study compares the ‘clock-drawing test’ to two standardized cognitive screens in an elderly population. A newly developed hierarchical classification of errors in clock-drawing correlated well with the severity of scores on both cognitive and screens and also demonstrated acceptable standards for sensitivity and specificity. Clock-drawing appears to be a practical test which can be useful for clinicians as a screen for cognitive impairment in old age and possibly as a marker of change in cognitive status.     

Altered behavior in experimental cortical dysplasia

Purpose: Developmental delay and cognitive impairment are common comorbidities in people with epilepsy associated with malformations of cortical development (MCDs). We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function. Methods: Fetal rats were exposed to 2.25 Gy external radiation on embryonic day 17 (E17). At 1 month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task, and the Morris water maze task. Key Findings: Rats with CD showed reduced nonlocomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex‐ and hippocampus‐dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model. Significance: This study documents multimodal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem.     

Abnormal dynamics of language in schizophrenia

Language could be conceptualized as a dynamic system that includes multiple interactive levels (sub-lexical, lexical, sentence, and discourse) and components (phonology, semantics, and syntax). In schizophrenia, abnormalities are observed at all language elements (levels and components) but the dynamic between these elements remains unclear. We hypothesize that the dynamics between language elements in schizophrenia is abnormal and explore how this dynamic is altered. We, first, investigated language elements with comparable procedures in patients and healthy controls. Second, using measures of reaction time, we performed multiple linear regression analyses to evaluate the inter-relationships among language elements and the effect of group on these relationships. Patients significantly differed from controls with respect to sub-lexical/lexical, lexical/sentence, and sentence/discourse regression coefficients. The intercepts of the regression slopes increased in the same order above (from lower to higher levels) in patients but not in controls. Regression coefficients between syntax and both sentence level and discourse level semantics did not differentiate patients from controls. This study indicates that the dynamics between language elements is abnormal in schizophrenia. In patients, top-down flow of linguistic information might be reduced, and the relationship between phonology and semantics but not between syntax and semantics appears to be altered.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

颈动脉狭窄与认知功能障碍研究进展

动脉粥样硬化可引起颈动脉内膜中膜厚度（IMT）的增加、斑块形成,导致颈动脉狭窄。约9％的60岁以上老年人出现动脉粥样硬化引起的颈动脉狭窄,颈动脉狭窄不仅是短暂性脑缺血发作、脑梗死等脑血管疾病的重要危险因素,而且颈动脉狭窄与认知功能受损相关。本文主要对颈动脉狭窄与认识功能障碍的临床及动物实验研究进展进行综述。