认知过程中的表观遗传学机制

该文首先对什么是表观遗传学及其细胞学基础作了介绍,随后,对认知功能中的表观遗传学机制的研究进展进行了综述。各方面研究一致证明,在海马、皮层及其它脑区发生的表观遗传学改变如组蛋白的乙酰化、甲基化、磷酸化、泛素化、多聚(ADP-核糖)聚合酶化和DNA甲基化可稳定地改变动物的行为,包括学习、记忆、突触可塑性、抑郁、药物成瘾等。不过,在长记忆和突触可塑形成过程中,需要CREB结合蛋白CP的存在并与CREB相结合,最后导致与记忆及突触可塑性有关的基因(如Zif/268,Greb,Bdnf,Reelin等)的转录和表达。相反,在衰老和神经退行性疾病脑内出现表观遗传学的异常改变,如组蛋白低甲基化、组蛋白去乙酰化转移酶活性增加等。鉴于上述,对神经退行性疾病的治疗策略是:提高组蛋白乙酰化和组蛋白、DNA甲基化,应用HDAC抑制剂及RNA干扰(RNAi)可有效地改善记忆,提高突触可塑性和阻遏学习记忆下降。     

PET network abnormalities and cognitive decline in patients with mild cognitive impairment.

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.     

围术期认知护理对老年认知功能的影响

目的观察进行围术期认知护理对老年患者术后认知功能的影响。方法择期髋关节置换手术患者30例,年龄65～89岁,患者术前认知护理干预从术前3d开始,术后认知护理干预从术后1d开始,于术前1d、术后1d、3d记录MMSE评分。结果术后第1d有3例发生POCD(10%);与术前比较,术后第1天MMSE评分降低(P<0.05)。结论髋关节置换手术老年患者术后认知功能有改变;围术期认知护理对老年患者术后认知功能的影响不能确定。     

阿立哌唑与认知行为联合应用于首发精神分裂症患者对认知功能的改善作用

目的为有效改善精神分裂症患者认知功能,探讨阿立哌唑、认知行为联合应用治疗对患者认知功能的改善效果。方法本次研究对象为2013年7月~2014年9月期间我院收治的70例首发精神分裂症患者,按照病床单双号分为药物对照组35例、观察组35例。药物对照组口服阿立哌唑,观察组在此基础上进行认知行为干预,观察两组患者治疗效果。结果观察组精神恢复有效率为94.3%较对照组80.0%好,观察组患者疾病症状、认知能力改善程度较对照组好(P<0.05);治疗前两组PANSS、SDSS评分比较差异无统计学意义(P>0.05),治疗后观察组较对照组疗效好(P<0.05)。结论临床对精神分裂首发患者采用阿立哌唑、认知行为联合应用治疗疾病,患者认知功能改善效果明显。     

Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment

In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.     

认知量表联合颅脑磁共振对维持性透析患者认知功能的评价

目的 探讨简易精神状态量表（MMSE）和蒙特利尔认知评估量表（MoCA）联合颅脑磁共振（MRI）弥散加权成像（DWI）/扩散张量成像（DTI）对透析患者认知功能的评估价值。方法 选择2015年5月至2016年5月于安徽医科大学第二附属医院肾内科进行透析的患者65例,采用MMSE和MoCA评估患者认知功能,MRI扫描脑白质区并计算表观弥散系数（ADC）和部分异向性（FA）量化值;根据MoCA结果分为认知正常组（38例）和认知障碍组（27例）,比较两组患者量表评分、ADC值及FA值的差异性。结果 MoCA检出率高于MMSE,差异有统计学意义（χ²=17.725,P=0.001）,且MMSE和MoCA总分呈正相关（r=0.660,P=0.001）。认知障碍组患者MMSE评分的定向力、记忆力、注意力、语言和总分低于认知正常组,而MoCA评分的执行力、注意力、语言、延迟回忆、定向力和总分均低于认知正常组,差异有统计学意义（P<0.05）;额叶和顶叶ADC值高于正常组,额叶、顶叶、胼胝体及侧脑室FA值低于正常组,差异有统计学意义（P<0.05）。结论 多认知量表联合评估可提高透析患者认知障碍的检出率;且存在认知障碍的透析患者主要表现为执行力、定向力、注意力、语言和记忆力的下降,和大脑额叶、顶叶、胼胝体和侧脑室白质的损伤相对应。     

Treatment of cognitive deficits in schizophrenia

Cognitive deficits are a core feature of schizophrenia and are a major contributor to functional disability. These impairments persist even when patients are in remission of psychotic symptoms and have, to date, eluded treatment. While some improvement is noted with existing medications, current trends in this field include studying and searching for adjunctive treatments to truly remediate cognitive dysfunction in schizophrenia. Psychosocial treatments have demonstrated some success, but the use of existing cognitive enhancers in schizophrenia treatment has provided little cognitive improvement. This paper reviews the current status of cognitive deficit treatment in schizophrenia and offers suggestions for future work.     

Estrogen and cognitive aging in women

The steady increase in female life expectancy has attracted attention to the importance of preventing cognitive aging and Alzheimer's disease (AD) in women. Evidence from randomized, controlled trials and from cross-sectional and longitudinal studies shows that estrogen-replacement therapy preferentially protects against a decline in verbal memory in healthy postmenopausal women and decreases the risk of AD. Although results are not consistent across studies, they indicate that treatment with estrogen during the postmenopausal years might protect against cognitive aging in women during the latter part of their life.     

Antidepressants in states of cognitive dysfunction

Several approaches are described for the design of pharmacologic strategies for the manipulation of cognition. By a variety of criteria, it is concluded that antidepressants deserve a trial in some patients with cognitive dysfunction. Depression is an illness with prominent cognitive dysfunction that shares, to some extent, cognitive and biochemical impairments similar to those observed in cognitive dysfunction of organic etiology. Antidepressants appear to produce their beneficial effect on cognition in depression by inducing slow adaptive changes in catecholamine and indoleamine pathways, therein promoting alterations in the individual's central motivational state. Animal data supporting these ideas are reported. As reviewed, few satisfactory studies of antidepressants in cognitive dysfunction of organic etiology appear in the literature, perhaps as the result of the potent anticholinergic properties of the most popular antidepressant drugs.     

认知护理干预对脑梗死轻度认知障碍患者认知功能的影响

目的对认知护理干预对脑梗死轻度认知障碍患者认知功能的影响进行初步研究。方法选取2017年1月～2018年10月我院收治的脑梗死轻度认知障碍患者90例,随机分两组,观察组45例和对照组45例。对照组采取常规治疗和护理,观察组在对照组的基础上给予认知护理干预。通过比较干预后两组患者的MMSE与ADL评分,比较两组的认知功能及精神状态的区别。结果观察组与对照组比较,干预前两组MMSE评分比较,差异无统计学意义(P 0.05),干预后观察组MMSE评分明显高于对照组,差异有统计学意义(P 0.05);观察组与对照组比较,干预前两组ADL评分比较,差异无统计学意义(P 0.05),干预后观察组ADL评分明显低于对照组,差异有统计学意义(P 0.05)。结论认知护理干预对脑梗死轻度认知障碍患者认知功能及精神状态有明显的改善,对于缓解脑梗死患者的认知障碍具有重要的临床参考价值,值得在医院推广应用。     

Non-pharmacological cognitive enhancement

The term "cognitive enhancement" usually characterizes interventions in humans that aim to improve mental functioning beyond what is necessary to sustain or restore good health. While the current bioethical debate mainly concentrates on pharmaceuticals, according to the given characterization, cognitive enhancement also by non-pharmacological means has to be regarded as enhancement proper. Here we summarize empirical data on approaches using nutrition, physical exercise, sleep, meditation, mnemonic strategies, computer training, and brain stimulation for enhancing cognitive capabilities. Several of these non-pharmacological enhancement strategies seem to be more efficacious compared to currently available pharmaceuticals usually coined as cognitive enhancers. While many ethical arguments of the cognitive enhancement debate apply to both pharmacological and non-pharmacological enhancers, some of them appear in new light when considered on the background of non-pharmacological enhancement. This article is part of a Special Issue entitled 'Cognitive Enhancers'.     

轻度认知功能障碍患者认知功能与氢质子磁共振波谱的相关性

目的 探讨轻度认知功能障碍(MCI)患者认知功能与氢质子磁共振波谱(1H-MRS)的相关性.方法 选取2020年1月至12月在沈阳市精神卫生中心住院及门诊就诊的20例MCI患者作为MCI组,选取同期在医院住院和门诊就诊的15例阿尔茨海默病(AD)患者作为AD组,选取同期认知功能正常的20例老年志愿者作为对照组.对三组研...     

载脂蛋白Eε4等位基因与轻度认知损害患者认知功能的缺损有关

目的 探讨轻度认知损害（MCI）患者认知功能改变以及认知功能改变和载脂蛋白E（ApoE）ε4等位基因的关系。方法 应用神经心理学方法评估患者的认知功能状况，应用分子生物学的方法进行APOE的基因型检测。结果 ①除记忆力显著下降外。MCI组定向力、语言能力、执行等能力也呈下降趋势。②MCI组ε4等位基因出现的频率远高于正常老年组（P〈0.01）。③ApoEε4的携带者的认知功能的总评分显著低于非ApoEε4携带者（P〈0．001）。除记忆力表现出显著下降外，ApoEε4携带组的语言能力、执行也呈下降趋势（P〈0．05）。结论 轻度认知功能损害患者的认知功能出现改变，且ApoEε4等位基因出现的频率显著高于正常老年组。ApoEε4等位基因与老年人认知功能的下降相关。     

齐拉西酮联合计算机认知矫正治疗对青少年精神分裂症患者认知功能的影响

目的 探讨齐拉西酮联合计算机认知矫正治疗对青少年精神分裂症(SCH)患者认知功能的影响.方法 选取2019年11月至2020年11月营口市第四人民医院收治的94例青少年SCH患者作为研究对象,采用随机数字表法将其分为研究组与参照组,每组各47例.参照组患者予以齐拉西酮治疗,研究组患者在对照组的基础上实施计算机认知矫正治...     

Recent advances in treating cognitive impairment in schizophrenia

Introduction

Schizophrenia is often associated with chronic disability and poor outcome. In addition to positive symptoms, such as hallucinations and delusions, and negative symptoms including poverty of speech and blunted affect, schizophrenia is also associated with deficits in cognitive function. It has been increasingly recognized that the severity of cognitive impairment is a major determinant of outcome. Therefore, interventions to improve cognitive function also have the capacity to improve quality of life and social and occupational outcomes. Whilst some of the antipsychotic drugs have shown some selective benefits, there is some controversy about the extent of these benefits.

Objectives

This article provides an overview of research into drugs that might enhance cognition in schizophrenia.

Conclusion

Drugs such as modafanil and galantamine are being evaluated, and a number of new drugs are currently in development. Standardized cognitive assessment measures are being developed so studies can be compared more easily. This field is advancing rapidly, but as yet, no widely applicable, evidence-based treatments are available to the clinician.     

血清睾酮对老年男性轻度认知功能损害患者认知功能的影响

目的探讨老年男性轻度认知功能损害(MCI)患者血清睾酮水平与认知功能的关系。方法35例轻度认知功能损害男性患者,年龄:78．7±6．1岁。用韦氏成人记忆量表(WMS)和简易智力状态检查量表(MMSE)进行认知功能检查;用化学发光法测定血清睾酮浓度;应用多元线性回归分析各项认知功能与血清睾酮浓度的关系。结果轻度认知功能损害患者血清睾酮浓度与MQ、MMSE评分呈正相关(P＜0．01),主要与视觉再生能力、触摸能力、理解记忆能力和延迟回忆力、语言能力有关(P＜0．01,P＜0．05)。结论血清睾酮水平可选择性影响MCI患者的认知功能,主要影响视空间和言语等能力。     

Minocycline reverses diabetes-associated cognitive impairment in rats

BackgroundMinocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats.MethodsHigh fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment.ResultsWe induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment.ConclusionsMinocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.     

Oxymatrine attenuates diabetes-associated cognitive deficits in rats

Aim： Oxymatrine （OMT） is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait （the Chinese herb Kushen） and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline （DACD） in a rat model of diabetes and explored the mechanisms of action. Methods： Male Wistar rats were injected with streptozotocin （65 mg/kg, ip） once to induce diabetes. The rats were then treated with vehicle or OMT （60 or 120 mg/kgper day, ip） for 7 weeks. Memory function was assessed using Morris water maze test. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD）, glutathione （GSH）, NF-KB p65 unit, TNF-a, IL-113 and caspase-3 in the cerebral cortex and hippocampus were quantified. Results： The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress （significantly increased MDA, decreased SOD and reduced GSH levels）, as well as significant increases of NF-KB p65 unit, TNF-（x, IL-113 and caspase-3 lew.~ls in the cerebral cortex and hippocampus. Chronic treatment with OMT dose- dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats. Conclusion： Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades.