阿尔茨海默病诊断标准的演变及意义

阿尔茨海默病（AD）的诊断标准经历了从 1984 年最初的诊断标准到 2018 年基于 A/T/N 分 类系统的 AD 研究框架的演变。诊断标准的不断更新,让人们更加了解 AD 这个疾病,也认识到了早期 诊断和生物标记物的重要意义。AD 是一个连续的疾病谱这一概念已经深入人心,生物标记物的纳入使 得疾病的诊断不断前移。在 AD 临床前期早发现、早诊断、早干预,必将为 AD 的研究带来新的希望。     

阿尔茨海默病发病机制与诊断治疗方法关联性研究进展

神经细胞外β淀粉样蛋白（Ap）沉积和神经细胞内神经纤维缠结（NFTs）是阿尔茨海默病（AD）早期特征性病理标志,并可能导致继发性神经元丢失和轴突退行性变。目前临床诊断主要集中在病史、神经系统检查、神经心理评估来进行定量和定性分析,不能对临床前期AD做出有效评价,AD患者脑中出现上述病理改变后数年甚至数十年后才会出现临床症状。因此,若能针对AD病理进展的病理标记物早期诊断和关键靶点进行干预,对AD的疗效及预后有极为重要的作用。     

阿尔茨海默病和轻度认知障碍患者脑网络变化特点的研究进展

阿尔茨海默病（AD）是一种隐匿性进展的神经退行性疾病,而轻度认知障碍（MCI）是AD发病前一个重要的临床前阶段。静息态功能磁共振（rs-fMRI）能在疾病早期反映脑网络变化,可作为研究AD及MCI的有效手段。本文综述了以rs-fMRI研究为基础的AD及MCI患者默认网络,注意网络,执行控制网络等的变化特点,为AD的早期诊断及干预提供依据。     

轻度认知功能障碍的神经影像学最新研究进展

轻度认知功能障碍（mild cognitive impairment，MCI）是介于正常老化、痴呆之间的一种临 床状态，表现为轻度的记忆和智能损害，达不到痴呆诊断标准，但有进展为痴呆的高风险。因此，早 发现、早诊断、早治疗非常关键。在MCI的具体诊断上，神经影像诊断表现出显著的临床应用价值， 该诊断方式在早期诊断MCI及预防AD疾病的发生上具有显著作用。本文综述了当前国内外应用神经 影像学诊断MCI的方法与结果，为进一步诊断及治疗MCI提供依据。     

临床前期阿尔茨海默症的早期诊断与干预

随着人口老龄化的加剧,以阿尔茨海默病（Alzheimer Disease,AD）为主的老年认知障碍问题日趋严重.作为一种多因素、多阶段并有伴随疾病的临床综合征,老年认知障碍在临床症状出现后将进展成不可逆性痴呆.因此,在无症状性临床前期AD症（PCAD）阶段进行早期诊断与干预成为了国内外研究的热点.现对PCAD的危险因素和针对其诊断干预的探索性研究进行综述,试图寻找在早期病理进程中新的可用于临床早期诊断的生物标记物及早期干预的药物靶点.     

主观认知下降的相关因素及其与Alzheimer’s病进展的关系

主观认知下降(SCD)指个体持续自我感知认知功能下降,但相关神经心理检测均在正常范围,可能是Alzheimer’s病(AD)疾病谱中最早可被发现的临床前阶段。SCD的影响因素众多,如何早期识别AD进展型SCD以便进行超早期干预是目前研究的重点。本文旨在对SCD的相关概念、临床特征、相关影响因素及其与AD进展的关系进行总结分析,从而为后续的相关研究提供参考。     

阿尔茨海默病患者脑电图与听觉认知电位P300的相关性研究

目的：观察阿尔茨海默病（AD）患者脑电图（EEG）与听觉认知电位P300的变化,并与神经心理学及痴呆程度进行相关性分析,探讨对老年性痴呆进行综合评价的有效方法。方法：对AD患者36例及正常对照者36名采用EEG和P300检查,结合神经心理学测试[简易智能精神状态量表（MMSE）]进行相关性分析。结果：AD组患者的P300潜伏期明显延长,波幅明显降低,与正常对照组比较差异有显著统计学意义（P〈0.01,P〈0.05）;EEG异常率AD组为84%,正常对照组为21 %,两组比较差异有显著统计学意义（P〈0.01）。MMSE总分AD组为19.77±5.22,明显低于对照组（27.66±5.13）,差异有统计学意义（P〈0.05）。AD组MMSE评分与P300 PL呈负相关（r=-0.57,P〈0.05）,与P300 AMP呈正相关（r=0.37,P〉0.05）。结论：利用EEG和P300结合MMSE量表可对老年性痴呆患者作出确切评价,是早期发现AD的有效手段之一。     

缺氧与阿尔茨海默病:低氧诱导因子-1的作用

阿尔茨海默病(Alzheimer's disease,AD)是最常见的老年神经变性疾病,其临床诊疗重视“早期发现、早期诊断、早期治疗”.体液或脑内有特定的AD生化、病理等改变,但未出现临床症状的AD称为临床前期阿尔茨海默病(Preclinical AD,PCAD).确定PCAD的危险因素,并进行早期干预对AD的防治有重要意义.缺氧是临床上常见的疾病病理过程,也是AD等多种神经变性疾病的重要危险因素.缺氧导致AD或促进AD病程进展的可能机制受到了广泛的关注和研究,本文就缺氧导致β-淀粉样蛋白(Aβ)沉积、tau蛋白异常磷酸化和神经元变性死亡的机制进行了综述,着重讨论了低氧诱导因子(hypoxia inducible factor 1,HIF-1)在其中的复杂作用.     

MoCA和MMSE在轻度认知障碍中的应用比较

轻度认知障碍（mild cognitive impairement,MCI）是痴呆的前期或早期,向AD的转化率较高,其早期诊断对防治AD具有重要意义。认知筛查量表在MCI诊断中具有重要作用。此文对蒙特利尔认知评估量表（montrealcognitiveassessment,MoCA）的主要内容及其特点进行综述,并与目前应用最为广泛的筛查量表简易精神状态检查量表（mino—mental state examination,MMSE）进行对比。     

血管内皮生长因子改善阿尔茨海默病认知功能障碍的研究进展

大脑中细胞衰老和葡萄糖代谢异常是阿尔茨海默病（AD）的早期特征,这种特征可能先 于 β 淀粉样蛋白沉积或 tau 蛋白磷酸化出现。血管内皮生长因子（VEGF）可通过营养神经、提高大脑的 葡萄糖代谢水平、抵抗 β 淀粉样蛋白对神经元细胞的毒性作用缓解 AD 患者的认知功能障碍。本文对 VEGF 改善 AD 患者认知功能障碍的作用机制进行综述,以期加深临床对疾病的认识,为探索新的治疗 靶点及治疗手段提供参考依据。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Summary of legislation of 1935 of interest to the department of Mental Hygiene

Psychiatric Quarterly -