老年期抑郁症的单光子发射计算机断层扫描研究

目的 了解老年期抑郁症(ED)的脑血流灌注特点,为相关神经科学理论提供实验室数据。方法 对26名健康老人、22例ED及26例阿尔茨海默病(Alzheimer’s disease,AD)患者作脑血流灌注检查。结果 与健康老人相比,ED存在右顶叶、双侧额叶和双侧枕叶低灌注(P<0.05),与AD相比,ED的扣带回、双侧颞叶、双侧基底节和双侧丘脑灌注明显较高(P<0.05)。ED在颞叶、额叶、枕叶和丘脑处的双侧灌注不对称(P<0.05),除丘脑灌注为左侧高于右侧外,其余均为左侧低于右侧。判别分析结果为右顶叶、左颞叶、左额叶、左枕叶和扣带回进入判别方程,ED的判别方程对ED诊断的敏感性和特异性分别为100％和94.2％。结论 ED脑血流灌注兼具一般抑郁症和本身的特点,右顶叶、左颞叶、左额叶、左枕叶和扣带回灌注对ED的诊断有重要意义,支持额叶、边缘系统及其它相关区域共同构成情绪调节回路的假设。     

A descriptive study on constructional impairment in frontotemporal dementia and Alzheimer's disease

Background and purpose:  Frontotemporal dementia (FTD) is a degenerative disorder characterized, in its frontal variant, by psychiatric onset, deficits in executive functions and sparing of memory and visuo-spatial abilities. Studies on visuo-spatial abilities in FTD and Alzheimer's disease (AD) have mainly focused on constructional abilities (CA) and have yielded contrasting data, often depending either on the task used or biases in the clinical selection of patients. The aim of our study was to evaluate the frequency of the CA impairment in FTD-fv and AD patients at the early stage of the disease, and to verify if some distinctive features of this impairment can characterize each pathology.
Methods:  The copy-drawing task (Rey Complex Figure, RCF) of 41 patients with probable mild AD and 15 patients with probable mild FTD-fv were analysed by means of quantitative and qualitative indices.
Results:  Data showed that both AD and FTD patients displayed similar RCF scores, as well as execution strategies, type of errors and global analysis. The FTD group only had a significant deficit in the analysis of inner details.     

The attitudes and practices of general practitioners regarding dementia diagnosis in Ireland

BACKGROUND: The diagnosis of dementia poses difficulties for general practitioners (GPs) particularly when access to specialist diagnostic services is delayed. Ireland is soon to witness an increase in numbers of people presenting with dementia, yet little is known about the service needs of GPs when attempting to diagnose dementia. OBJECTIVES: To detail the service needs of GPs, especially their training needs, access to diagnostic resources such as CT and MRI brain scans and access to specialist services such as Old Age Psychiatry (OAP), Geriatric Medicine (GM) and Neuropsychology (NP). METHODS: The paper is based on survey data collected from a sample of GPs (n = 300) registered with the Irish College of General Practitioners (ICGP) and on qualitative data collected from a Focus Group (n = 7). RESULTS: GPs were more likely to blame themselves than either the health care system, their patients or family members for the late presentation of dementia in primary care. Stigma was a major obstacle preventing GPs from being more proactive in this area. Rural GPs felt geographically disadvantaged accessing diagnostic services and both rural and urban GPs experienced considerable time delays accessing specialist diagnostic services. CONCLUSIONS: Findings provide compelling evidence that training and access to diagnostic services are only two of several different structural and ideological obstacles that GPs encounter when attempting to diagnose dementia. Future educational supports for GPs need to be developed which concentrate on these areas.     

中枢胆碱能系统损害对脑自由基水平的影响

在中枢胆碱能系统损害所致的Alzheimer病模型中,观察不同时期脑组织自由基水平的变化。结果表明,随着时间的推移,中枢胆碱能系统变性逐渐加重,所测到的动物自由基代谢紊乱也越明显;与胆碱能系统联系最密切的海马区超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH—PX)活性下降最显著。而自由基代谢紊乱反过来又可能加重神经递质代谢障碍,促使或加重Alzheimer病(AD)的进程。     

多发梗死性痴呆与阿尔次海默病认知功能损害及有关因素的比较研究

目的探讨多发梗死性痴呆(MID)与阿尔次海默病(AD)在认知功能损害及有关因素方面的差异,为早期诊断、鉴别诊断提供依据。方法 对113例MID患者与78例AD患者作简易智力状态检查量表(MMSE)测查,及研究其发病有关因素并作比较。结果 MMSE总分MID组为(17.43±6.1)分高于AD组的(13.30±5.30)分;定向力、语言命名、注意计算、短程记忆、物体命名、语言复述、阅读理解、语言表达、图形描记因子分MID组均高于AD组;MID组平均血压值高,高血压史、中风史、局灶性神经系统体征明显,急性、亚急性起病、病程呈波动特点为多。结论 MMSE测查结果结合有关病史是MID早期诊断及与AD鉴别诊断的重要依据。     

脑啡肽酶基因多态性与阿尔茨海默病及血管性痴呆的相关性研究

目的 探讨陕西延安地区汉族人群中脑啡肽酶(NEP)基因多态性与阿尔兹海默(AD)和血管性痴呆(VD)的相关性。方法 选择2013年1月-2016年6月在本科治疗的138例AD患者作为AD组,57例VD患者作为VD组,同时随机选择同期在本院体检的老年体检健康者150例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)结合DNA直接测序法检测NEP基因rs989692位点和rs6776185位点基因型。结果 各组NEP基因rs989692位点基因型和等位基因分布频率无明显差异(P均>0.05)。对于rs6776185位点AD组和VD组与对照组比较,AA基因型和A等位基因分布频率均明显增多(P均<0.05)。AD组与VD组基因型和等位基因分布频率无明显差异(P均>0.05)。结论 NEP基因rs6776185位点A等位基因和AA基因型可能是陕西延安地区汉族人AD和VD发病的危险因素。     

Neurofibrillary tangles in patients with Down's syndrome: A light and electron microscopic study

Summary Two older patients with Down's syndrome and widespread neurofibrillary tangles and senile plaques were studied by light and electron microscopy. The ultrastructural demonstration of twisted tubules verified the assumption that the tangles encountered in these patients were Alzheimer's neurofibrillary tangles. Despite the morphological evidence of Alzheimer's disease, neither of these patients were clinically demented.     

The identification of pathological subtypes of Alzheimer's disease using cluster analysis

A culster analysis was performed on 78 cases of Alzheimer's disease (AD) to identify possible pathological subtypes of the disease. Data on 47 neuropathological variables, inculding features of the gross brain and the density and distribution of senile plaques (SP) and neurofibrillary tangles (NFT) were used to describe each case. Cluster analysis is a multivariate statistical method which combines together in groups, AD cases with the most similar neuropathological characteristics. The majority of cases (83%) were clustered into five such groups. The analysis suggested that an initial division of the 78 cases could be made into two major groups: (1) a large group (68%) in which the distribution of SP and NFT was restricted to a relatively small number of brain regions, and (2) a smaller group (15%) in which the lesions were more widely disseminated throughout the neocortex. Each of these groups could be subdivided on the degree of capillary amyloid angiopathy (CAA) present. In addition, those cases with a restricted development of SP/NFT and CAA could be divided further into an early and a late onset form. Familial AD cases did not cluster as a separate group but were either distributed between four of the five groups or were cases with unique combinations of pathological features not closely related to any of the groups. It was concluded that multivariate statistical methods may be of value in the classification of AD into subtypes.     

Promotion of self-management in friendship

This study examines changes in self management abilities among women in a friendship enrichment programme. The study is based on the theory of self management of well-being which identifies relevant self-management skills as self-efficacy, taking initiative, investment behaviour and attaining variety in resources. An intervention group (N = 60) and a control group (N?=?55) were studied at a baseline, three months and nine months later. Results indicate that the programme is effective in stimulating two of the four self-management abilities. Compared to the control group, participants in the intervention showed greater increases in initiative taking and more investment behaviour in friendship. There was no change in self-efficacy or variety in friendship. We conclude that older adult women are able to improve some self-management abilities in friendship after participating in this programme. Important goals for future studies are to improve the measurement of self-efficacy and relate improvement in self-management to subjective well-being.     

阿尔茨海默病早期生物学诊断标志物研究进展

阿尔茨海默病(Alzheimer's disease,AD)是老年性痴呆最常见的类型之一,随着年龄的增长,其患病率不断增高[1].虽然病理学研究早已证实,AD患者脑内的病理生理变化始于中年时期,但目前的临床现状是大部分患者在老年期或老年前期因为出现相关的认知功能障碍症状才被发现,而且通常已是疾病的中晚期,从而导致了干预的延迟和干预效果不理想.造成这种现象的最主要原因之一是AD脑内病理的变化和临床症状在时间上的分离,即症状的出现远远滞后于病理生理学的改变.     

Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls

Summary There is increasing evidence that the neurodegenerative processes in Alzheimer's disease (AD) may be related to alterations in calcium homeostasis and that these metabolic changes are not necessarily restricted to the central nervous system. However, previous studies investigating [Ca²⁺]_i in fibroblasts, lymphoblasts, platelets and lymphocytes of AD patients gave inconclusive results, since increase, decrease and no alteration in [Ca²⁺]_i were found in AD patients compared with controls. With respect to the importance of establishing altered Ca²⁺ homeostasis in peripheral cells, we have investigated [Ca²⁺]_i in circulating mononuclear cells of patients with AD, multi-infarct dementia, age-associated memory impairment and healthy controls. [Ca²⁺]_i was evaluated using the fluorescent dye fura-2 before and during stimulation with phythaemagglutinin (PHA). In our study we failed to find major differences in resting [Ca²⁺]_i and in response to stimulation with 25g/ml and 100 g/ml PHA in cells of AD patients as compared with all other groups investigated. There was only a tendency towards a decrease in [Ca²⁺]_i in AD after stimulation with PHA. Thus the present findings suggest that [Ca²⁺]_i evaluation in mononuclear cells does not have diagnostic value in discriminating AD patients from other demented patients. However, there might be some difference in, [Ca²⁺]_i values between early- and late-onset AD, which could have pathophysiological importance.     

A novel mutation (Thr116Ile) in the presenilin 1 gene in a patient with early-onset Alzheimer''s disease

We report a novel presenilin 1 (PSN1) mutation (Thr116Ile) in a woman with early onset Alzheimer's disease (AD). This mutation was not found in 100 healthy controls, indicating that this is not a common polymorphism. The patient presented with forgetfulness at age 45, followed over the next 3 years by a worsening of the memory loss and frequent episodes of confusion and spatial disorientation. Neuroimaging studies were consistent with AD. The analysis of the family's pedigree showed that the proband was apparently the only member affected. Because the early death of several close relatives (i.e. the mother and the grandmother) and the demonstration that the father is not a mutation carrier, it is suggested that either a de novo mutation or a censor effect might have occurred. Our finding supports the indication that PSN1 mutations should be searched for in early-onset AD, particularly when a censor effect precludes a precise genetic analysis.     

冈田酸对拟AD模型大鼠海马CA1区Aβ1-40和nNOS表达的影响

目的观察冈田酸(OA)对大鼠海马CA1区Aβ1-40和nNOS表达的影响,建立更接近临床表现的拟AD大鼠模型。方法在大鼠海马CA1区多次微量注射OA,水迷宫实验观测大鼠行为学改变;Bielschowsky染色观察海马CA1区神经原纤维缠结(NFT)和老年斑(SP)等特征性病理变化;免疫组化方法观察海马CA1区Aβ1-40和nNOS的表达。结果模型组学习记忆减退;海马CA1区出现NFT(P<0.05)和SP特征性病理变化,及Aβ1-40的高表达(P<0.05)和nNOS的低表达(P<0.05)。结论冈田酸海马CA1区微量多次注射,可建立更接近AD临床表现和病理特征的大鼠模型,大鼠海马CA1区SP和NFT的形成,以及Aβ1-40表达增加、nNOS表达减少,是该模型大鼠学习记忆能力减退的可能机制。     

Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease

Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms.     

阿尔茨海默病正电子发射计算机断层扫描和神经心理测定的初步研究

目的 探讨阿尔茨海默病(Alzheimer’s disease,AD)的脑葡萄糖代谢、神经心理学特点及AD的正电子发射计算机断层扫描(positron emission photography,PET)诊断。方法 对13例AD患者和11例年龄、性别和文化程度相匹配的健康对照者(HC)进行PET检查、简易智能状态检查(mini-mental state examination,MMSE)、韦克斯勒记忆量表测定(wechsler memory scale,WMS)和日常生活能力量表(activity of daily living,ADL)测定。结果 ①AD组MMSE、WMS分值明显低于HC组(P<0.01)。②肉眼读片,AD组存在脑萎缩,尤其是颞叶萎缩;大脑皮层放射性分布不均匀;健康老人可出现顶叶局部脑葡萄糖代谢率(regional cerebral metabolism rate of glucose,rCMRglc)的减低,但程度较轻;AD组全脑rGMRglc减低,以顶叶为最明显,其次为颞叶,再次为额叶。③AD组在双侧额叶上、中、下回、眶回、直回、颞叶中下回、顶上小叶、缘上回、前扣带回、尾状核、岛叶、丘脑,左侧角回、左侧杏仁核等脑区rCMRglc半定量指标降低较明显,与健康对照组相比,差异具有显著性或高度显著性((P<0.05-P<0.001);AD组病人额叶上中下回葡萄糖代谢半定量指标降低最为明显,其次为丘脑和尾状核。④相关分析表明,MMSE评分与性别呈负相关(P=0.025);右侧顶上小叶和右侧丘脑的rCMRg     

阿尔茨海默氏病与血管性痴呆临床特点的对照研究

目的比较阿尔茨海默氏病（AD）与血管性痴呆（VD）的临床特点。方法对39例AD和38例VD患者的精神行为症状特点、伴随的躯体疾病、头颅CT检查以及脑电图检查进行比较。结果AD组与VD组在幻觉、妄想等精神病性症状方面无明显差异,在抑郁、焦虑等情绪障碍以及行为脱抑制方面有显著差异;AD组伴随的躯体疾病无明显特异性,VD组多伴发高血压、冠心病;AD组头颅CT多表现为脑萎缩,VD组多表现为脑梗塞;脑电图检查AD组无明显特异性,VD组界限脑电图居多。结论AD与VD患者的BPSD及所伴随的躯体疾病可有不同特点,CT和脑电图的检查等对痴呆的诊断与鉴别诊断均具有重要价值。     

Brain vasopressin levels in Down Syndrome and Alzheimer''s Disease

Performing gene hunting in Down Syndrome fetal brain we detected an overexpressed sequence highly homologous to the human vasopressin gene. As this neuropeptide may be involved in the pathogenetic mechanism and, moreover, was described to play a role in memory and learning, we decided to study the brain gene product level in Down Syndrome (DS), controls and patients with Alzheimer's disease (AD). Subtractive hybridization was used to study the differential expression between steady state mRNA levels in fetal brain of DS and controls at the 23rd week of gestation. A radioimmunological method was used to determine vasopressin (AVP) in five brain regions of each 9 aged DS brains, 9 brains with AD and 9 control individuals, obtained from brain bank. An overexpressed nucleic acid sequence with 91% homology to the vasopressin gene was detected in both fetal brains with DS. AVP levels in controls were of the order cerebellum>occipital>frontal>parietal>temporal lobe and were significantly higher in temporal lobe and lower in cerebellum of patients with DS. AVP levels in brain of AD patients were also significantly increased in temporal lobe but were not reduced in cerebellum. The biological meaning of increased AVP remain unclear but may be linked to the neurodegenerative processes, proposed to be similar in both disorders. Data from gene hunting in fetal DS brain along with our data on aged DS and AD patients suggest the early involvement of AVP in the pathomechanism accompanying cholinergic, monoaminergic and neuropeptidergic deficits described in DS and AD.