Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are stil unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cel ular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/tyrosine kinase activity is able to modulate cel signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebel um and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebel um. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as wel as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed fol owing atorvastatin treatment.

Brain structure and cognitive function change in the temporal lobe, hippocampus, and prefrontal cortex of patients with mild cognitive impairment and Alzheimer’s disease, and brain network-connection strength, network efficiency, and nodal attributes are abnormal. However, existing research has only analyzed the differences between these patients and normal controls. In this study, we constructed brain networks using resting-state functional MRI data that was extracted from four populations mal controls, patients with early mild cognitive impairment, patients with late mild cognitive impairment, and patients with Alzheimer’s disease) using the Alzheimer’s Disease Neuroimaging Initiative data set. The aim was to analyze the characteristics of resting-state functional neural networks, and to observe mild cognitive impairment at different stages before the transformation to Alzheimer’s disease. Results showed that as cognitive deficits increased across the four groups, the shortest path in the rest-ing-state functional network gradual y increased, while clustering coefficients gradual y decreased. This evidence indicates that dementia is associated with a decline of brain network efficiency. In tion, the changes in functional networks revealed the progressive deterioration of network function across brain regions from healthy elderly adults to those with mild cognitive impairment and Alzhei-mer’s disease. The alterations of node attributes in brain regions may reflect the cognitive functions in brain regions, and we speculate that early impairments in memory, hearing, and language function can eventual y lead to diffuse brain injury and other cognitive impairments.

Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebel um of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22-24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebel um. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebel um. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.

Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mi-tochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mi-tochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These de-tected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, isova-leryl-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyl-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are al involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production.

OBJECTIVE: This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hal ucination of patients with schizophrenia spectrum disorders.
DATA SOURCES: Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Control ed Trials databases from January 1985 to May 2012. Key words were “transcranial magnetic stimulation”, “TMS”, “repetitive transcranial magnetic stimulation”, and “hal ucination”.
STUDY SELECTION: Selected studies were randomized control ed trials assessing therapeutic ef-ficacy of repetitive transcranial magnetic stimulation for hal ucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hal ucination in schizophrenia spectrum disorders. Control groups received sham stimulation.
MAIN OUTCOME MEASURES: The primary outcome was total scores of Auditory Hal ucinations Rating Scale, Auditory Hal ucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hal ucination item, and Hal ucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function.
RESULTS: Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. Al data were completely effective, involving 398 patients. Overal mean weighted effect size for repeti-tive transcranial magnetic stimulation versus sham stimulation was statistical y significant (MD =-0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P =0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repeti-tive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching.
CONCLUSION: Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hal ucination in schizophrenia spectrum disorders.

老年髋部骨折后发生谵妄的研究现状

谵妄是老年髋部骨折术后常见的并发症之一，其致死率、致残率均较高，但相对于下肢深静脉血栓、肺栓塞、心力衰竭等疾病，谵妄尚未得到大家足够的重视。本文就髋部骨折后谵妄的定义、诊断、发生率、预后、预防、治疗等方面进行综述，希望可以更好地认识及了解谵妄。谵妄是一种急性精神障碍，以意识、注意力、知觉、思考能力、记忆力、心理活动、情感以及睡眠-觉醒周期的共同紊乱为特征，而且这些改变很难用老年痴呆来解释。虽然诊断谵妄的方法较多，但常用的是意识状态评估法（confusion assessment method, CAM），即主要依靠患者的意识及认知功能对谵妄进行诊断及评估。老年髋部骨折后谵妄发生率较高，高可达61%。导致谵妄发生的机制尚不明确，学说众多，目前认为谵妄是由多种因素共同作用的结果，影响因素主要有高龄、认知功能损害、疼痛、睡眠节律失常等，涉及学说主要有神经递质学说、中枢炎性假说、应激反应学说、睡眠-觉醒周期障碍学说等。关于谵妄对髋部骨折术后死亡率的影响，目前尚没有统一结论，但可以肯定的是谵妄患者术后功能恢复差，独立生活能力差，需要更长卧床时间，更多人进行护理。对谵妄应以预防为主，尽可能纠正低氧血症，减轻疼痛，避免水电解质紊乱，改善睡眠节律，避免使用阿片类药物，同时采用包括骨科、麻醉科、老年科等在内的多学科协作模式可能会减少谵妄的发生率。而谵妄一旦发生，应首选非药物治疗，如保持呼吸道通畅、充足的营养支持、纠正水电解质紊乱、贫血和低白蛋白血症、保证充足睡眠和精神支持、创造优良的病区环境等；一旦病情加重，出现躁动、幻觉、注意力不集中等症状，可使用药物治疗来减轻其发病症状，首选氟哌啶醇。

交流对老年人认知功能的影响

随着老龄化社会的到来,国内外对老年人认知功能障碍的研究越来越重视[1].国内老年人认知功能障碍患病率为1.31%～11.36%[2].随着城市化进程的加快和空巢老人的不断增多,由此引发的老年人身居高楼,孤独、缺乏情感交流的现象也日益突出.

发育性协调运动障碍儿童执行功能的横断面研究

背景 发育性协调运动障碍(developmental coordination disorder,DCD)患儿存在明显的运动能力、学习和日常生活能力的下降.国外研究表明,患儿的这些能力下降与其认知功能尤其是执行功能的受损有关,但国内尚无此类研究来证实这些结果.目的 比较发育性协调运动障碍患儿与正常儿童的执行功能.方法 对2008年3月至2010年3月在杭州市第七人民医院就诊并符合DSM-IV发育性协调运动障碍诊断的39例患儿采用威斯康星卡片分类测验(Wisconsin Card Sorting Test,WCST)进行评估.另外,在杭州某小学随机抽取39名健康儿童作为对照组,同样对他们进行WCST评估.结果 两组在WCST的总应答数及非持续错误数相似,但是研究组的错误应答数、持续性应答数和持续性错误数均显著高于对照组.另外,研究组患儿完成分类数低于对照组,完成第一个分类所需的应答数也高于对照组.结论 本研究证实了先前一些研究的结果,即发育性协调运动障碍患儿存在明显的执行功能缺陷.所有这些研究均提示,患儿的执行功能缺陷显著影响了其智能和社会功能的发展.

慢性精神分裂症住院患者辅以认知矫正治疗的随机对照研究

背景 认知矫正治疗(Cognitive Remediation Therapy,CRT)是一种很有希望的、新的非药物治疗方法,能够减少精神分裂症患者的认知缺损.但未在国内得到充分的验证.目的 探讨认知矫正治疗对慢性精神分裂症患者认知功能、社会功能及自知力的疗效.方法 将126例病情相对稳定的慢性精神分裂症住院患者随机分成干预组和对照组.干预组接受行认知矫正治疗,对照组接受常规的工娱治疗,两组在治疗频度和治疗持续时间一致,均为每周5次,共3个月.于治疗前及治疗末分别采用威斯康星卡片分类测验(Wisconsin Card Sorting Test,WCST)评估认知功能,采用住院慢性精神分裂症患者社会功能评定量表(Scale of Social Skills of chronic schizophrenia Inpatients,SSSI)评估社会功能以及采用自知力与治疗态度问卷(Insight and Treatment Attitude Questionnaire,ITAQ)评估自知力.结果 研究过程中有 4 例患者脱落,干预组 60 例、对照组 62 例终进入结果分析.治疗 3 个月后,两组的WCST测评结果均较治疗前显著改善,而干预组的WCST各指标的改善均比对照组明显.两组在 3 个月治疗后的SSSI总分均显著改善,但改善程度在两组间无显著性差异;两组的ITAQ总分也均有提高,但干预组的改善程度比对照组更明显.结论 在药物治疗的基础上,为期3个月的认知矫正治疗对改善慢性精神分裂症住院患者的认知功能及自知力比常规的工娱治疗更为有效.

中国精神分裂症认知功能的研究进展

认知功能障碍-精神分裂症的核心症状之一-已经成为国内外研究精神分裂症的热点。它不仅反映了疾病的严重程度，而且是精神分裂症功能预后的重要影响因素，因为认知功能损害的程度对患者的独立生活能力以及他们的就业和社会功能都会有影响。国内早的精神分裂症认知功能研究可以追溯到上个世纪七十年代晚期。近年来，由于新的信息的出现，例如神经影像技术的进步，国内涌现了大量研究。本文在对国内既往研究进行综述的基础上提出了精神分裂症认知功能的未来研究方向。

精神分裂症认知功能障碍的脑网络组研究

Impaired cognitive function, along with positive and negative symptoms, is a core clinical feature of schizophrenia. Earlier studies suggest that impaired cognitive functioning should be assessed from the perspective of brain networks. The recently developed brainnetome approach to evaluating brain networks-an approach that was initially developed by Chinese scientists-provides a new methodology for studying this issue. In this paper we first introduce the concept of brainnetome. We then review recent progress in developing a brainnetome of impaired cognitive function in people with schizophrenia. The models of the relevant brain networks considered were created using data obtained from functional and anatomical brain imaging technologies at different levels of analysis: networks centered on regions of interest, networks related to specific cognitive functions, whole brain networks, and the attributes of brain networks. Finally, we discuss the current challenges and potential new directions for research about brainnetome.

痴呆的精神行为症状的管理——并非易事

Management of the behavioral and psychological symptoms of dementia (BPSD) is a hot topic because these commonly seen symptoms in persons with dementia are quite difficult to manage.As highlighted in the comments by Xiao[1],the administration of antipsychotics is controversial because the use of antipsychotic medications in persons with dementia is associated with increased mortality,increased risk of stroke and worsened cognitive function[2,3].Xiao recommends that more long-term follow-up studies on the management of the BPSD be conducted to give clinicians better guidance on the treatment of this complex condition.This recommendation is particularly pertinent for Chinese populations.Two studies from Hong Kong showed that patients with the BPSD who were treated with antipsychotic medications did not have an increased risk of cerebrovascular accidents[4]or mortality[5].Clearly,more studies should be conducted in populations of different ethnicity to confirm or disprove the presumed risks of antipsychotic medications in patients with dementia.

新抗癫癎药影响认知功能的研究进展

近10年来,对癫癎的研究迅速发展,临床上出现了一批新的抗癫癎药物(AEDs),如奥卡西平、氨己烯酸、拉莫三嗪、唑尼沙胺、加巴喷丁、硫加宾、托吡酯和左乙拉西坦.与传统的抗癫癎药物相比,疗效相似,而耐受性更好.另外几个新抗癫癎药物的疗效相近,治疗谱相似.癫癎患者需要长年用药,甚至终身服药,因此,选择抗癫癎药物主要是基于药物的耐受性、避免对身体和精神的不良反应、防止对患者认知功能的损害.认知功能损害是影响癫癎患者生活质量的主要因素之一.

抗癫痫药物对认知功的影响

认知功能是指接受、加工、储存和应用信息的能力.它是人们成功地完成各种活动重要的心理条件.理解力、记忆力、注意力、学习能力、警觉和想象能力等均被认为是重要的认知能力[1].癫痫患儿的认知能力受癫痫发作、社会心理因素、抗癫痫药物(AEDs)等多种因素的影响.儿童较成人而言,由于大脑兴奋性和抑制性尚未达到平衡,更易罹患癫痫,且更易发生认知功能障碍.AEDs在减低致痫神经元兴奋性的同时亦降低了正常神经元的兴奋性,从而损伤认知功能.

The change of serum folic acid,homocysteine and its relationship with cognitive function in first episode schizophrenia

Objective To observe the change of serum folic acid,homocysteine (Hcy) and its relationship with cognitive function in first episode schizophrenia (SZ).Methods Forty-five patients with first episode schizophrenia treated in our hospital from March 2014 to June 2015 were selected as the observation group,and 50 healthy adults were selected as the control group.The serum level of folic acid,Hcy and cognitive function were observed in two groups.The correlation between them was analyzed by Pearson correlation analysis.Results The level of folic acid of the first episode SZ patients was significantly lower than that of the control group,while the Hcy level was significantly higher than that of the control group,and the difference was statistically significant (P＜ 0.05);The scores of orientation,instantaneous memory,attention,word immediate memory and delayed recall of the observation group were significantly lower than those of the control group (P＜0.05);The level of folic acid was positively correlated with orientation,instantaneous memory and attention and calculation,while the Hcy level was negatively correlated with the indexes mentioned above;the folic acid,homocysteine (Hcy) level had no obvious correlation with language ability,visual and spatial perception and word immediate memory.Conclusions The level of serum folic acid of the patients with first episode SZ are lower and the level of serum Hcy is higher,and the above indexes are closely related with some cognitive functions of the patients.