脑衰反应调节蛋白2的生理作用及其与阿尔茨海默病的关系

阿尔茨海默病（AD）的主要病理特征包括大脑中淀粉样斑块（淀粉样前体蛋白的β样剪切）和神经纤维缠结（tau蛋白的高度磷酸化）.近年来,为了深入探讨AD患者记忆和认知缺陷的发病机理,许多研究者试图寻找与AD病理发展相关的早期分子机制.研究发现,脑衰反应调节蛋白（CRMP）是一种广泛表达于成人和婴幼儿大脑中的蛋白,而且伴随着AD的病理发展,CRMP2出现了明显的异常磷酸化.现就CRMP2的生理作用与AD的关系综述如下.     

粒细胞集落刺激因子对阿尔茨海默病大鼠脑内炎症的影响

目的探讨粒细胞集落刺激因子(G-CSF)治疗阿尔茨海默病(AD)大鼠对脑内炎症反应的影响。方法 54只Wistar雄性大鼠(3~4个月龄),随机选取18只作为正常组、36只制作AD大鼠模型成功后采用随机数字表法各选取18只分别作为治疗组、模型组;模型组和正常组采用HE染色法对大脑皮层组织进行观察,治疗组给予G-GCS(0.3 ml·kg-1·d-1),模型组和正常组分别给予等量磷酸盐缓冲液(PBS)注射,又分别于第7、14、21天进行相关指标的检测并进行组间比较。结果正常组治疗第7、14、21天的大脑皮层细胞IL-1β染色光密度值均显著低于模型组、治疗组(P0.05),治疗组治疗14、21 d后大脑皮层细胞IL-1β染色光密度值低于模型组(P0.05)。正常组治疗第7、14、21天的大脑皮层细胞TNF-α染色光密度值均显著低于模型组、治疗组(P0.05),治疗组治疗14、21 d后大脑皮层细胞TNF-α染色光密度值低于模型组(P0.05)。结论 AD大鼠对脑内炎症反应作用显著增强,G-CSF可以有效降低AD大鼠的炎症反应作用,对大鼠大脑皮层细胞具有一定的保护作用。     

康复综合治疗对阿尔茨海默病患者脑电特征影响的研究

目的探讨康复综合治疗对阿尔茨海默病(AD)患者脑电特征的影响。方法选择AD患者30例,按照随机数字表法分为治疗组15例和对照组15例。2组患者进行相同药物治疗,治疗组患者在药物治疗基础上增加康复综合治疗。于治疗前、治疗3个月后分别进行简易智能状态检查量表(MMSE)、Barthel指数(BI)及脑电特征分析,比较2组测评结果及相关性。结果治疗组治疗后MMSE、BI评分较治疗前及对照组治疗后明显提高,差异有统计学意义(P<0.05);治疗组治疗后脑电信号高频带相对功率比值较治疗前和对照组治疗后明显增加[β1:(1.254±0.331)vs(0.883±0.204)、(0.853±0.287);β2:(1.033±0.256)vs(0.679±0.413)、(0.628±0.117),P<0.05]。脑电高频带β1、β2相对功率比值与MMSE评分呈正相关(r=0.67,r=0.57,P<0.01),与BI评分相关性较低(r=0.34,r=0.30,P<0.05)。治疗组治疗后δ、θ频带比值较治疗前明显降低,α、β频带比值较治疗前明显增高(P<0.05),对照组治疗前后各频带比值无明显变化。结论康复综合治疗对于改善AD患者认知及日常生活活动能力具有积极作用,通过脑电特征分析可客观评价康复治疗效果。     

深部脑磁刺激技术治疗阿尔茨海默病的临床研究

目的 探讨深部脑磁刺激技术(dTMS)治疗阿尔茨海默病患者(AD)的有效性及安全性. 方法 AD患者116例和年龄相匹配的健康对照组33例,AD患者随机分为(1)dTMS组dTMS真刺激治疗；(2)药物组给予盐酸多奈哌齐5 mg/d治疗；(3)联合治疗组同时给予dTMS和盐酸多奈哌齐药物治疗；(4)空白对照组伪刺激治疗.健康对照组dTMS真刺激治疗.疗程6个月.应用简明精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、汉密尔顿抑郁量表(HAMD)、缺血量表(HIS)、听觉词语测试、词语流畅性测试、数字广度测试、画钟测验(CDT)、Boston命名测试、韦氏积木图、日常行为能力量表(ADL)及神经精神问卷(NPI)评价dTMS治疗的疗效和安全性.结果 dTMS组、药物组和联合治疗组治疗6个月后MMSE、MoCA、ADL、NPI及认知亚项评分均较空白对照组改善(t值MMSE分别为2.49、2.46、2.20,t值MoCA分别为2.59、2.39、2.87,t值ADL分别为2.35、2.17、2.83,t值NPI分别为3.05、2.40、2.65,均P＜0.05),联合治疗组各量表评分较药物组和dTMS组认知功能和日常行为能力改善(均为P＜0.05),但dTMS组、药物组及联合治疗组治疗后各量表评分仍较健康对照组差(P＜0.05). 结论 dTMS可以有效安全地治疗AD患者的认知及非认知症状,为AD提供非药物治疗手段.     

电刺激对阿尔茨海默病患者脑功能、NPI及MMSE评分的改善作用

目的 探究经颅直流电刺激(tDCS)对阿尔茨海默病(AD)患者脑功能、神经精神量表(NPI)及简易精神状态检查(MMSE)量表评分的改善作用。方法 选取96例AD患者按抽签法均分为两组,对照组给予常规治疗,观察组在对照组基础上联合tDCS治疗。观察两组汉密顿抑郁(HAMD)量表、AD评价量表-认知分量表(ADAS-cog)、MMSE、NPI及日常生活能力量表(ADL)评分,并使用功能性磁共振成像(fMRI)技术对两组治疗前后进行扫描。结果 治疗后,观察组HAMD评分、ADAS-cog评分、NPI评分显著低于对照组,MMSE评分、ADL评分显著高于对照组(P<0.05);治疗后观察组左侧楔前叶短程连接密度(LFCD)较治疗前增强。结论 tDCS可使AD患者左侧楔前叶LFCD增强,并减轻患者抑郁症状,提高患者认知功能,改善患者神经精神症状及日常生活能力。     

脑老化及阿尔茨海默病患者脑中突触密度改变的研究

目的　观察正常人增龄过程中突触素表达的变化 ,研究脑老化中不同部位突触密度的改变 ,并与阿尔茨海默病 (AD)患者比较。方法　应用突触素免疫组织化学方法 ,观察 2 8例正常增龄病例 (2 3～ 10 0岁 ,分为成年组 ,老年组 ,>75岁组 )尸检脑标本的额叶、枕叶、壳核、海马及 6例AD患者 (AD组 )的海马标本。测算 3组各部位突触素密度 ,并分析其与年龄之间的相关性 ,比较 >75岁组与AD组海马CA3区突触素密度的差异。结果　老年组脑额叶、枕叶、壳核及海马CA3区突触密度与年龄呈负相关。AD组海马CA3区突触密度低于 >75岁组且差异有显著性意义 ,P <0 .0 1。结论　脑老化过程中额叶、枕叶、海马CA3区与壳核突触密度随年龄增加下降 ,AD组突触密度较正常增龄病例有所降低。     

阿尔茨海默病患者的脑淀粉样血管病变

脑淀粉样血管病变 (cerebralamyloidangiopathy ,CAA)是由淀粉样蛋白在软脑膜及脑皮质血管内沉积所致〔1〕。1975年报道 ,在尸检的阿尔茨海默病 (AD)患者脑内有87%CAA〔2〕。 1984年 ,一种与AD有关的CAA中的β淀粉样蛋白 (Aβ)被确认〔1〕。Aβ蛋白由 39～ 4 2个氨基酸的肽链构成。老年斑 (SP)中的Aβ蛋白长臂主要是 4 2～ 4 3对碱基 ,而脑血管性Aβ蛋白则主要为 39～ 4 0对碱基。Aβ蛋白沉积在大脑实质形成SP或神经炎斑 ,沉积在血管壁则导致脑淀粉样血管病变。CAA至今被认为是AD最常见的血管性病理改变 ,80 %～ 10 0 %AD患者脑…     

很可能的阿尔茨海默病患者血清C反应蛋白和β淀粉样蛋白的水平变化

目的研究很可能的阿尔茨海默病(AD)患者血清C反应蛋白(CRP)和β淀粉样蛋白(Aβ)的水平变化。方法入选53例临床确诊为很可能的AD患者为研究组,48例非AD者为对照组。记录受试者的一般临床特征,行简易智能精神状态检查量表(MMSE)和临床痴呆评级笔盒评分(CDR-SOB)测试,并测定CRP和Aβ水平。结果与对照组相比,研究组年龄较大(P<0.05),教育程度显著降低(P<0.05)。与研究组相比,对照组MMSE表现较好(P<0.05),且临床痴呆评定量表(CDR)总分和CDR-SOB得分显著降低(P<0.05);CRP水平显著降低(P<0.05),Aβ40和Aβ42水平显著降低(P<0.05)。多元线性回归模型分析显示,对于研究组患者,CRP水平降低显著预测较高的CDR-SOB得分(P=0.020 3),Aβ水平与较差的MMSE得分和CDR-SOB得分有关(P<0.05)。在对照组线性回归模型中,CRP水平与较差的MMSE得分和CDR-SOB得分有关(P<0.05),Aβ水平与较差的CDR-SOB得分有关(P<0.05)。结论很可能的AD患者CRP水平与血Aβ水平显著降低,CRP水平降低与AD患者较差的CDR-SOB得分有关,Aβ水平与较差的MMSE得分和CDR-SOB得分有关。     

低频脉冲电刺激联合常规康复训练对阿尔茨海默病患者吞咽功能的影响

目的 探究低频脉冲电刺激联合常规康复训练对阿尔茨海默病(AD)患者吞咽功能及营养指标的影响。方法 120例老年AD患者随机分为对照组和观察组各60例。对照组行常规康复训练,观察组在对照组基础上增加低频脉冲电刺激治疗。比较两组临床疗效、进食并发症及治疗前后舌肌活动度及血氧饱和度(SaO₂)下降值、吞咽功能[洼田饮水试验、电视透视吞咽功能检查(VFSS)]、营养指标[血清白蛋白(ALB)、血红蛋白(Hb)]。结果 观察组临床总有效率明显高于对照组(P<0.05)。与对照组相比,观察组治疗后舌前伸、左右运动度明显更高,SaO₂下降值则明显更低(P<0.05);观察组洼田饮水试验评分更低、VFSS评分则更高(P<0.05)。观察组治疗后ALB、Hb水平均明显高于对照组(P<0.05)。观察组咳呛、误吸、肺炎发生率均明显低于对照组(P<0.05)。结论 低频脉冲电刺激联合常规康复训练可有效改善AD伴吞咽障碍患者的吞咽功能及营养状况,降低进食并发症发生率,疗效显著。     

Clinician assessment of the driving competence of patients with dementia

OBJECTIVES: To determine the validity and reliability of clinician ratings of the driving competence of patients with mild dementia. DESIGN: Observational study of a cross-section of drivers with mild dementia based on chart review by clinicians with varying types of expertise and experience. SETTING: Outpatient dementia clinic. PARTICIPANTS: Fifty dementia subjects from a longitudinal study of driving and dementia. MEASUREMENTS: Each clinician reviewed information from the clinic charts and the first study visit. The clinician then rated the drivers as safe, marginal, or unsafe. A professional driving instructor compared these ratings with total driving scores on a standardized road test and categorical ratings of driving competence. Clinicians also completed a visual analog scale assessment of variables that led to their determinations of driving competence. RESULTS: Accuracy of clinician ratings ranged from 62% to 78% for the instructor's global rating of safe versus marginal or unsafe. In general, there was moderate accuracy and interrater reliability. Accuracy could have been improved in the least-accurate raters by greater attention to dementia duration and severity ratings, as well as less reliance on the history and physical examination. The most accurate predictors were clinicians specially trained in dementia assessment, who were not necessarily the most experienced in their years of clinical experience. CONCLUSION: Although a clinician may be able to identify many potentially hazardous drivers, accuracy is insufficient to suggest that a clinician's assessment alone is adequate to determine driving competence in those with mild dementia.     

Prediction of on-road driving performance in patients with early Alzheimer's disease

OBJECTIVES: Physicians and family members frequently are asked to provide information about driving ability in patients with Alzheimer's disease (AD), yet there has been little research on the validity of their assessments of driving performance. DESIGN: Cross-sectional. SETTING: Participants were recruited from the neurology department of a community hospital affiliated with Brown Medical School. PARTICIPANTS: Participants included 75 older adults (17 with mild AD, 33 with very mild AD, and 25 elderly controls). MEASUREMENTS: The participant him/herself, an informant, and an experienced neurologist rated each participant's driving ability on a 3-point rating scale (safe, marginal, unsafe). A professional driving instructor also completed a standardized 108-point on-road driving assessment of each participant and then rated driving ability on the 3-point scale. Ratings were compared with the on-road driving score and with each other. RESULTS: Only the neurologist's rating of the participants' driving abilities was significantly related to on-road driving score. When related to the instructor's safety rating, the neurologist's ratings were the most sensitive and specific. Mini-Mental State Examination score was a borderline covariate for the neurologist's rating. Overall, the instructor was the most stringent rater of participant driving ability, followed by the neurologist, the informant, and the participant. CONCLUSION: An experienced neurologist's assessment of driving competence may be a valid predictor of driving performance of patients with early AD.     

老年性痴呆的治疗进展

老年性痴呆是导致老年人认知功能持续减退的最常见的疾病，目前该病唯一应用的治疗方法是用胆碱酯酶抑制剂。随着对AD分子和细胞病理生理的进一步了解，又发展了医一些新的治疗方法，如分泌酶抑制剂、过渡金属元素螯合剂、HMG-CoA还原酶抑制剂和B淀粉样蛋白疫苗等。本文综述了近几年来的老年性痴呆治疗方面的进展。     

老年性痴呆的诊断进展

老年性痴呆(AD)是一种以痴呆为主要临床表现的脑变性疾病。目前早期诊断主要根据临床表现进行排除性诊断,缺乏客观的实验室指标作为“金标准”。本文就当前AD诊断方法研究进展,特别是生物学、神经影像学及电生理检查在AD诊断中的意义及其相应敏感性和特异性进行评述。     

IL-6启动子多态性与阿尔茨海默氏病的相关性探讨

目的 探讨细胞因子白介素6(IL—6)与阿尔茨海默氏病(AD)的相关性。方法 用PCR—RFLP技术检测356例英国AD患者和434例对照者IL-6启动子-174C／G多态性，并进行了对比分析。结果 IL-6启动子-174C／G多态性与AD无相关性。其与AD发病年龄、β淀粉样蛋白沉积量和小神经胶质细胞含量无明显相关性。结论 IL-6启动子-174C／G多态性不是AD的危险因素。     

老年性痴呆与健康老人的脑电图、脑电地形图比较

目的比较老年性痴呆患者（AD）与健康老人的脑电图（EEG）和脑电地形图（BEAM）特点。方法对35例AD患者和32例健康老人的EEG和BEAM检查结果进行比较。结果AD患者组EEG、BEAM的异常率分别为77．14％和80．95％。明显高于健康老人组的27．77％和33．33％,差异有统计学意义（P〈0．01）;AD患者中α节律慢化、泛化、低至中波幅,θ波弥漫性活动,δ波活动增多比例均明显高于健康老人组（P〈0．05）;AD患者随病情加重EEG、BEAM的中度异常率明显升高（P〈0．05）。结论EEG、BEAM检查可以作为AD常规临床检查和评价指标之一,有助于对病情严重程度及进展的判断。     

Longitudinal driving performance in early-stage dementia of the Alzheimer type

OBJECTIVES: To longitudinally assess on-road driving performance in healthy older adults and those with early-stage dementia of the Alzheimer type (DAT). DESIGN: A prospective longitudinal study. SETTING: Large urban medical center and surrounding area. PARTICIPANTS: A sample of 58 healthy controls, 21 participants with very mild DAT, and 29 participants with mild DAT participated. DAT was diagnosed using validated clinical diagnostic criteria and staged according to the Clinical Dementia Rating (CDR) Scale. MEASUREMENTS: Healthy controls and individuals with very mild DAT and mild DAT were administered a standardized on-road driving assessment over repeated times of testing. RESULTS: Subjects in the CDR=1 group (mild DAT) had a faster rate of receiving a rating of not safe on the driving test than subjects in the CDR=0 group (healthy controls; log rank test, P=.006), and the survival function of the CDR=0.5 group (very mild DAT) fell between those of the CDR=0 and CDR=1 groups. A Cox proportional hazards model indicated a significant difference in survival functions between the CDR=0 and CDR=1 groups after baseline age was controlled for (P<.001). Cox regression analysis also indicated that baseline age was a significant risk factor for a rating of "not safe" (P=.002). CONCLUSION: This study provides longitudinal evidence for a decline in driving performance over time, primarily in early-stage DAT, and supports the need not only for driving assessments, but also for reevaluation of individuals with very mild and mild DAT.     

Cognitive profiles and response to donepezil treatment in Alzheimer's disease patients

Background:   The aim of this study was to determine whether there are certain characteristic neuropsychological profiles, assessed by the Mini-Mental State Examination (MMSE) at baseline, which predict donepezil treatment response.
Methods:   A total of 112 consecutive outpatients with Alzheimer's disease (AD) were treated with donepezil for 3–4 months. Multiple regression analysis was performed to estimate the relative contributions of individual subscales at baseline to the MMSE change (study point – baseline). To identify the characteristic patterns in cognitive deficits of patients with AD who responded to donepezil therapy, the subscales of the MMSE at baseline of responders and non-responders were compared.
Results:   Multiple regression analysis revealed that lower scores on attention and calculation, and language function, and a higher scale on orientation (date) are related to an improvement of the MMSE. When an improvement of 4 or more points on the MMSE score was defined as a significant response, responders scored significantly lower than non-responders on attention and calculation, whereas non-responders scored significantly lower than responders on memory.
Conclusion:   Our results suggest that individual differences in patterns of neuropsychological impairments may partly contribute to the diversity of the response to donepezil treatment. Although further studies with more detailed neuropsychological tests are needed to confirm our results, the MMSE may add to the prediction of response to donepezil treatment in patients with AD.     

对氧磷酶2基因多态性与阿尔茨海默病的相关性研究

目的 探讨对氧磷酶2（paraoxonase 2,PON2）基因多态性（148Ala/Gly;311Cys/Ser）与Alzheimer病（AD）之间的关系.方法 用PCR-RFLP分析技术对132例AD患者和186例年龄匹配的健康对照者进行PON2 148Ala/Gly及311Cys/Ser基因多态性的分析.结果 PON2基因148、311位点存在多态性,其基因型频率和等位基因频率在AD患者和正常对照者间差异无显著性.结论 PON2基因多态性与AD未发现显著相关性.     

一种新的老年痴呆动物模型

目的：建立一种新的老年痴呆（AD）小鼠模型，用于AD及其治疗药物的研究。方法：选用NIH小鼠，腹腔注射D－半乳糖120mg/kg和亚硝酸钠90mg/kg，每天1次，连续60d，制备老年痴呆动物模型，通过水迷宫试验，脑组织匀浆蛋白质含量，乙酰胆碱酯酶（AchE)和超氧化物歧化酶（SOD）活性的测定，脑组织病理切片HE染色和刚果红染色，比较老年痴呆模型小鼠和正常小鼠的差异。结果：与对照组比，模型组小鼠的逃避潜伏期明显增加（P＜0．01），脑内蛋白质含量没有明显差异，脑内AchE活性增加（P＜0．01），SOD活性下降（P＜0．01），模型组小鼠出现触须脱落，大脑皮层出现类老年斑病理改变，海马和大脑皮层神经元变性坏死，结论：D－半乳糖和亚硝酸钠合并制备的老年痴呆模型在一定程度上模拟了AD的发病特点，可作为AD及其治疗药物研究的一种新模型。