应重视阿尔茨海默病的药物临床试验

阿尔茨海默病（Alzheimer disease，AD）的临床试验难度较大，存在的问题较多。某些实验设计不规范，出现非随机对照、无对照研究，甚至用回顾性研究来评估疗效；选用不能全面反映痴呆认知、功能、行为的量表作为评估指标；有的试验质控不严格；加之研究对象合作程度有限，在一定程度上影响了科学评估AD治疗药物的疗效和安全性。为此，我们根据循证医学原则，结合实际工作中的体会，就相关问题进行了归纳和分析。     

自闭症语言障碍的研究进展

自闭症患者的理解力比表达能力的损伤严重,交流能力非常有限,有言语自闭症患者的语音损伤最轻。应该从心理学起因,生物学病因方面对自闭症患者的语言障碍进行综合探讨。     

哈伯因治疗阿尔茨海默病的疗效观察

本文应用哈伯因对重度阿尔茨海默病（AD）患者进行为期1年的治疗，以评价其有效性。     

雌激素与阿尔茨海默病

雌激素与阿尔茨海默病洪霞张振馨李辉随着人口老龄化，老年期痴呆已成为全球重点公共卫生问题。阿尔茨海默病（ＡＤ）是引起痴呆的最常见原因。目前，ＡＤ的病因还不清楚，部分学者认为，绝经后雌激素水平减低与ＡＤ有一定联系。如果二者之间确实存在病因联系，口服雌激素...     

早发型阿尔茨海默病的影像学特点

阿尔茨海默病(Alzheimer’s disease, AD)是一种进行性加重、不可逆转的神经退行性疾病,其患病率随着人口年龄的增长而迅速增长。绝大多数AD患者的发病年龄在65岁之后,与此类常见的晚发型阿尔茨海默病(late-onset Alzheimer’s disease, LOAD)相比,约有5%～10%的AD患者在65岁之前出现认知障碍的症状,被定义为早发型阿尔茨海默病(early-onset Alzheimer’s disease, EOAD)。尽管LOAD、典型遗忘型EOAD及非典型EOAD有着相同的分子病理学,即淀粉样蛋白-β(Aβ)和tau的积累,但在临床表现上存在异质性。EOAD经常因非典型临床表现导致误诊或延迟诊断,且通常病情进展迅速,生存时间短,因此了解EOAD的特征对早期诊断和治疗尤为重要。不同临床表型的AD似乎在某些脑区存在选择性脆弱性,这可能为解释这种异质性提供了一个方向。本篇综述分析比较了近年来典型遗忘型及非典型EOAD结构、功能及分子成像的最新研究进展,探索影像学指标作为一种无创标志物的可行性及有效性,以期为EOAD诊断提供一些新思路。     

植物提取物治疗阿尔茨海默病的研究进展

本文综述了一些具有认知增强效应的植物或其活性成分，它们来自于中国、印度及日本等传统医学，并讨论了它们主要的药理作用。     

药物综合治疗阿尔茨海默病的临床观察

目的探讨药物综合治疗阿尔茨海默病的疗效.方法13例轻中度患者,用盐酸多奈哌齐、肠溶性阿斯匹林、氢化麦角碱和银可络综合治疗,持续12周.第6周和12周时进行疗效评估.结果治疗6周后11例有效(11/13)、12周后10例有效(10/13),两者的MMSE评分均比治疗前有显著意义的提高,主要是注意力、计算力评分及语言评分.而6周与12周之间的MMSE评分无显著差异.除个别患者出现胃肠道反应外无其他严重副反应.结论本组药物综合治疗可改善症状,近期效果肯定,且副反应小.远期疗效尚有待观察.     

阿尔茨海默病与血管性痴呆的临床特点

目的　观察比较阿尔茨海默氏病（ＡＤ） 与血管性痴呆（ＶＤ） 的临床特点,为临床上对老年期痴呆的诊断和鉴别诊断提供帮助。方法　根据ＤＳＭⅣ诊断标准,对２１ 例ＡＤ 患者、２５ 例ＶＤ 患者的临床特点进行对比研究,包括：疾病发展过程、认知功能、情感反应、行为变化和知觉异常。所有病人均为轻中度痴呆患者。结果　①ＡＤ 为缓慢起病;ＶＤ 多数起病较急。②ＡＤ 的认知功能减退常常累及多个方面;ＶＤ 以记忆力减退和计算力减退为主。③ＡＤ 的非认知功能常常受影响;ＶＤ的非认知功能较少受累。结论　ＡＤ 与ＶＤ 的临床特点不同,与两种疾病的病理机制不同有关。根据其不同的临床表现,有助于对这两种常见的老年期痴呆作出诊断及鉴别诊断。     

引导式教育在语言障碍患儿中的应用

目的 探讨引导式教育在语言障碍中的应用.方法 对50例语言障碍患儿进行引导式教育治疗及临床观察.结果 引导式教育是促进语言障碍恢复的相关因素.结论 语言障碍者需要进行引导式教育,引导式教育能明显改善语言障碍者的预后.     

阿尔茨海默病的神经再生研究进展

阿尔茨海默病（AD）是一种神经退行性疾病，其病理特征表现为β 淀粉样蛋白（Aβ）的异 常沉积，tau 蛋白异常磷酸化，以及由这些引发的神经元变性、坏死。已有研究表明海马神经再生与AD 息息相关，采用海马神经再生治疗AD已成为具有意义和前景的研究。现对AD 及海马神经再生之间的 关系进行综述。     

Astrocyte dysfunction in Alzheimer disease

Astrocytes are glial cells that are distributed throughout the central nervous system in an arrangement optimal for chemical and physical interaction with neuronal synapses and brain blood supply vessels. Neurotransmission modulates astrocytic excitability by activating an array of cell surface receptors and transporter proteins, resulting in dynamic changes in intracellular Ca²⁺ or Na⁺. Ionic and electrogenic astrocytic changes, in turn, drive vital cell nonautonomous effects supporting brain function, including regulation of synaptic activity, neuronal metabolism, and regional blood supply. Alzheimer disease (AD) is associated with aberrant oligomeric amyloid β generation, which leads to extensive proliferation of astrocytes with a reactive phenotype and abnormal regulation of these processes. Astrocytic morphology, Ca²⁺ responses, extracellular K⁺ removal, glutamate transport, amyloid clearance, and energy metabolism are all affected in AD, resulting in a deleterious set of effects that includes glutamate excitotoxicity, impaired synaptic plasticity, reduced carbon delivery to neurons for oxidative phosphorylation, and dysregulated linkages between neuronal energy demand and regional blood supply. This review summarizes how astrocytes are affected in AD and describes how these changes are likely to influence brain function. © 2017 Wiley Periodicals, Inc.     

中枢神经系统周细胞功能障碍参与阿尔茨海默病发病机制的研究进展

中枢神经系统周细胞主要分布于微血管周围,于1873年由Rouget首次发现,因此又称Rouget细胞[1-2].尽管被发现已超过150年,但周细胞的功能、特征、信号通路等方面的研究还远未明确.进入21世纪后,涌现出大量研究认为中枢神经系统周细胞是神经血管单元(Neurovascular Unit, NVU)的重要组成部分,其功能障碍参与包括缺血性脑卒中[3]、肌萎缩侧索硬化[4]、帕金森病[5]、创伤性脑损伤[6]、糖尿病视神经变性[7]、常染色体显性遗传病合并皮质下梗死和白质脑病(Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy,CADASIL)[8]等疾病的发生、发展.近年来,随着对于周细胞研究的深入,越来越多的文献支持其与阿尔茨海默病(Alzheimer Disease, AD)密切相关.本文即以AD的发病机制为出发点,就近几年来所报道的周细胞功能障碍参与AD的文献综述如下.     

外泌体在阿尔茨海默病中的研究进展

外泌体是一种纳米级细胞外囊泡,大多数细胞类型均可分泌,存在于血液、唾液、脑脊液和乳汁等体液中.阿尔茨海默病(AD)是一种起病隐匿的进行性发展的神经系统退行性疾病,给家庭和社会带来沉重的负担,其病因迄今未明.因外泌体可携带相应来源细胞的核酸、蛋白质等分子信息,所以在多种疾病诊治中有着强大的生物学功能.随着研究的深入,外泌体在AD中的作用成为近年来研究的热点,但也存在争议.研究发现,外泌体在AD中有多种作用:一方面,它可在细胞间传播毒性β淀粉样蛋白(β-amyloid,Aβ)和过度磷酸化tau蛋白(P-tau),并可能会诱导细胞凋亡从而造成神经元的丢失;另一方面,外泌体似乎能通过被胶质细胞摄取而减少大脑Aβ负荷.本文将简要介绍外泌体,并阐述其在AD中的研究进展.     

Alzheimer disease

In an attempt to determine the risks for and kinds of dementia most prevalent among the African American population, the Alzheimer's Disease Research Center at the University of Pittsburgh developed a community satellite program specifically targeting the African American and historically medically underserved communities in Allegheny County, PA. The primary mission of the Alzheimer Outreach Center (AOC) was to increase the awareness of AD among the targeted population. The number of nonwhite patients participating in the studies at ADRC increased from 2 to 16% in the first year of the program. In May 1995, the AOC became a permanent ADRC program.     

Neuronal binucleation in Alzheimer disease hippocampus

Aims: The literature and teachings instruct that neurones in the adult brain are fully differentiated, quiescent cells that never divide. Somewhat surprisingly, and counter to such dogma, susceptible neurones in Alzheimer disease display an activated cell cycle phenotype. However, whether this leads to a coordinated procession through the cell cycle is unclear, particularly whether neurones enter anaphase and beyond. To begin to address this issue, in this study we sought to determine whether nuclear division occurs in these neurones. Methods: We examined a series of 101 archived, routinely stained hippocampal sections collected at post mortem for neuropathological evaluation for evidence of neuronal binucleation. Results: We report for the first time, binucleated neurones within the hippocampus in cases of Alzheimer disease but not in control cases ( P  < 0.05). Conclusions: While a relatively rare event, occurring once every 20 000 neurones, this morphological evidence that neuronal cells within the cortical regions of the adult human brain in Alzheimer disease contain two nuclei supports the hypothesis that neuronal cells can re-enter into a coordinated cell cycle that culminates in nuclear division.     

Immune-activation model in Alzheimer disease

About 10 years ago, we implicated immune factors in the pathophysiology of Alzheimer disease (AD), the hypothesis being that AD may be an immunologically derived systemic disease, but clinical effects confined primarily to the brain. We originally hypothesized that an immune basis of the disease may involve faulty immune regulation and autoimmunity. As described here, the activation of immunoregulatory T-lymphocytes with CD8 phenotype may be important in the immunopathogenesis of the disease.     

经颅多谱勒检测阿尔茨海默病的对照研究

目的 了解阿尔茨海默病(AD)的颅内各大血管血流速度的改变情况,及其与认知功能改变之间的关系.方法 记录60例首次入院的AD患者经颅多谱勒(TCD)颅内血管检测结果,包括两侧大脑中动脉、两侧大脑前动脉、两侧大脑后动脉、基底动脉、两侧椎动脉.同时记录简易智力状态检查(MMSE)结果.对照组为60例血管性痴呆(VD)和60例精神分裂症(S).结果 研究组和对照组自身每一颅内动脉的两侧血流速度无显著差异(P＞0.05).AD组的TCD检测异常率为90.00%,其中以血流速度降低为突出表现,与VD组无显著性差异(P＞0.05),但明显低于S组(P＜0.01或0.05,两侧椎动脉除外).AD的颅内各动脉(右侧大脑后动脉除外)血流速度与简易智力状态检查(MMSE)分数呈正相关.结论 AD的TCD检测对该病的病因探讨、认知功能评估及治疗有一定意义.     

Asbestos exposure and Alzheimer disease

10 cases in which an asbestos-related disease (malignant pleural mesothelioma or asbestosis) was associated with severe Alzheimer type lesions in the brain are reported. The patients, all males aged between 67 and 78 years, had been occupationally exposed to asbestos in the shipbuilding industry. The hypothesis that asbestos in a favoring factor in the genesis of Alzheimer disease is discussed.

---

Sommario Vengono descritti 10 casi nei quali una malattia da asbesto (mesotelioma maligno da asbesto o asbetosi era associata a lesioni cerebrali tipo Alzheimer. I pazienti, tutti maschi di età compresa tra 67 e 78 anni avevano subito un'esposiione professionale all'asbesto avendo lavorato nell'industria navale. Viene discussa l'ipotesi che l'asbesto possa rappresentare un fattore favorente nella genesi della malattia di Alzheimer.

     

阿尔茨海默病神经影像学研究进展

阿尔茨海默病(Alzheimer Disease,AD),又称老年性痴呆,是一种病因复杂、隐匿起病的神经退行性疾病,主要临床表现为记忆障碍,同时伴有人格改变及思维语言障碍等神经精神症状,AD的特征性病理改变为β淀粉样蛋白(Aβ)沉积和神经元纤维缠结,以及神经元丢失伴胶质细胞增生等,这些病理改变破坏了大脑结构和功能.AD发病率高,平均生存周期只有5.5年.随着我国人口老龄化的快速发展,AD患者数量逐年增加,给家庭及社会带来越来越沉重的负担,因此,对AD做出早期诊断变得尤为重要.然而,AD起病隐匿,早期的临床表现并不突出,且实验室检查也缺乏足够的特异性,早期容易被漏诊和误诊,当临床医生做出明确诊断时,多数患者已处于AD的中晚期,这在一定程度上延误了AD的治疗,因此,对AD进行早期诊断,尽早进行治疗具有非常重要的意义.近年来,随着影像学技术的不断发展,为AD的早期诊断提供重要的影像学依据.现分别从结构性磁共振(sMRI)、静息态功能磁共振成像(Rs-fMRI)、磁共振弥散张量成像(DTI)、正电子发射计算机断层显像(PET)等几个方面,阐述影像学技术在AD早期诊断的研究进展.     

Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease

Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD).

Methods: We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed.

Results: Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement.

Conclusions: Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical–cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical–cortical circuits that occurs in PDD patients.

Abbreviations: AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia