Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline

Context  Alzheimer disease (AD) is characterized neuropathologically by the presence of amyloid -peptide (A)–containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of A correlates with dementia and whether A alterations precede or follow changes in tau. Objectives  To determine whether accumulation of A correlates with the earliest signs of cognitive deterioration and to define the relationship between A accumulation and early tau changes. Design, Setting, and Patients  Postmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of A variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia. Main Outcome Measures  Levels of total A peptides with intact or truncated amino termini and ending in either amino acid 40 (Ax-40) or 42 (Ax-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score. Results  The levels of both Ax-40 and Ax-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone Ax-42 peptide were higher than those of Ax-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in Ax-40 and Ax-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease. Conclusions  In this study, levels of total Ax-40 and Ax-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, A was elevated before the occurrence of significant tau pathology. These results support an important role for A in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of A should be pursued.      

电针对老年性痴呆大鼠胆碱能神经元损伤的保护作用

目的探讨电针对老年性痴呆(Alzheimer’sdisease,AD)大鼠胆碱能神经元损伤的保护作用及其作用机制。方法36只SD老龄大鼠随机分为正常对照组、假手术组、模型组和电针治疗组,采用穹隆-海马伞损伤法制作大鼠AD模型。电针治疗组施以电针百会、涌泉、太溪、血海等穴。采用放射免疫法检测脑中隔区胆碱乙酰转移酶(cholineacetyltransferase,ChAT)活性,免疫组化法检测海马CA3区神经生长因子(nervegrowthfactor,NGF)和c-fos蛋白的表达。结果电针治疗组ChAT活性高于模型组;电针治疗组NGF和c-fos蛋白的表达较模型组增加。结论电针对AD模型大鼠胆碱能神经元损伤的保护作用可能与促进c-fos合成及诱导海马NGF的表达相关。     

Using dementia rating scales in the diagnosis of Alzheimer''s disease

Objective: To study the significance of dementia rating scales in the diagnosis of Alzheimer' s disease (AD).Methods: Probable AD patients(118 cases) diagnosed according to NINCDS-ADRDA criteria and the normal controls(100 cases) were examined with a battery of neuropsychological tests and the dementia severity of AD patients was determined with clinical dementia rating(CDR). Changed neuropsychological characteristics of different AD dementia severities were analyzed. The discriminant analysis and ROC curve analysis were performed to analyze the specificity, the sensitivity, and the general accuracy of various dementia rating scales in the diagnosis of AD, and the area under the ROC curve. Results: The total cognition function in mild (CDR = 1), moderate(CDR = 2) and severe stages(CDR=3) of AD had an obvious trend of continuous decline, with the MMSE values 17.44 ± 2.64, 13.90 ± 4.32, and5.50± 3.90 respectively. The trend of decline of the verbal fluency function in AD was same as that of total cognition function. The visuospatial function was reduced in early stage of AD (CDR = 1 ) and completely lost in moderate and severe AD. Delay memory function began to show decline in the early stage of AD, and the decline turned apparent in moderate and severe AD. Immediate memory function showed unchanged in early stage of AD, while showed decline in moderate AD, and the decline became very quick in severe AD. The impairment of daily living ability and social activity function developed with the severity degree of AD. But the decline of social activity function was very quick in moderate stage of AD. In general, the leading scale to diagnose AD was FOM, followed by RVR, POD, MMSE, BD,ADL and DS. When MMSE was combined with one or more of FOM, RVR, BD, DS, the general accuracy in distinguishing AD from the normal controls was improved. Conclusion: Neuropsychological test is useful in the diagnosis of AD, especially in the early stage. The validity is improved when dementia rating scales are combined correctly.     

Spatial learning deficits in amyloid precursor protein 770 transgenic mice

Objective To determine whether learning deficits could be seen in transgenic mice expressi ng human amyloid precursor protein 770 (APP770).Methods Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group.All mice wer e subjected to various behavioral tasks including the Y-maze task and the Morri s water maze.After behavioral testing, the mice were sacrificed, and their bra in tissues were used for measuring the choline acetyltransferase (ChAT) activity . Results Nine-month-old transgenic mice exhibited spatial learning deficits in the Morr is water maze and in spontaneous alternation in the Y-maze, compared with those o f the age-matched non-transgenic mice.The behavioral changes accompanied a red uction of ChAT activity in the cortical and hippocampal regions of transgenic mi ce.On the other hand, these behavioral deficits were not observed in transgeni c mice either at 3 or at 6 months of age, in which ChAT activity remained unchan ged. Conclusions The present results show that the learning impairment observed in 9-month-old APP770 transgenic mice are accompanied by a decrease in cortical and hippo campal ChAT activities.This suggests that cholinergic deficits may be involved in the learning impairment observed in these APP770 mice.This model wi ll be a useful tool in advancing our understanding of the relationship between t he cholinergic system and the cognitive deficits observed in Alzheimer’s disease (AD).     

补肾益智方对阿尔茨海默病大鼠模型脑内胆碱能神经系统的保护作用

为探讨自制方补肾益智方 (由蛇床子、枸杞子、女贞子、人参、制首乌等组成 )治疗阿尔茨海默病(Alzheimerdisease ,AD)的可能神经生物学机制 ,应用乙酰胆碱酯酶组织化学染色方法 ,研究了该方对D -半乳糖合并鹅膏蕈氨酸损毁大脑Meynert基底核的实验性阿尔茨海默病大鼠模型脑内胆碱能神经系统的保护作用 ,结果显示 :补肾益智方灌胃组大鼠脑内广泛区域的乙酰胆碱酯酶阳性神经纤维密度较模型对照组增加 (P <0 .0 5或P <0 .0 1) ,提示该方对AD模型脑内胆碱能神经元具有一定的保护作用。     

Neurochemical characteristics of early and late onset types of Alzheimer's disease

Brains of 49 patients who had died with Alzheimer's disease and 54 controls were examined. The Alzheimer group exhibited noticeably reduced activity of the cholinergic marker enzyme choline acetyltransferase in the cerebral cortex, but cortical concentrations of noradrenaline, gamma-aminobutyric acid, and somatostatin were also significantly reduced. Analysis of the results according to age at death showed that the older patients, dying in their 9th and 10th decades, had a relatively pure cholinergic deficit confined to temporal lobe and hippocampus, together with a reduced concentration of somatostatin confined to temporal cortex. By contrast, the younger patients, dying in their 7th and 8th decades, had a widespread and severe cholinergic deficit together with the abnormalities of noradrenaline, gamma-aminobutyric acid, and somatostatin, and the younger patients accounted for most of the abnormalities in these systems observed in the overall group. Comparison of the young subjects with Alzheimer's disease with the older controls did not support the concept of Alzheimer's disease representing an acceleration of the aging process. These results suggest that Alzheimer's disease in people aged under 80 may represent a distinct form of presenile dementia which differs in important respects from the dementia of old age.     

Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

Background An important aspect of Alzheimer’s disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment.Methods Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status.Results ACh concentrations in CSF of AD patients ［(10.7±5.1） nmol/L］ and VD patients ［(16.8±7.4） nmol/L］ were both significantly lower than in controls ［(34.5±9.0） nmol/L, t=10.67, P&lt;0.001; t=6.91, P&lt;0.001］. Both results correlated positively with MMSE scores (rs=0.88 and rs=0.85, respectively, P&lt;0.01). The CSF concentration of Ch was significantly higher in VD patients ［(887.4±187.4） nmol/L］ compared to AD patients ［(627.6±145.1） nmol/L, t=6.4, P&lt;0.001］ and controls ［(716.0±159.4） nmol/L, t=4.2, P=0.002］. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups. Conclusions The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.     

不同程度阿尔茨海默病患者血脂水平的研究

目的 对不同程度首次接受药物治疗前的阿尔茨海默病(Alzhemer disease,AD)患者血脂水平[总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、血清高密度脂蛋白(serum high-density lipoprotein,HDL)、血清低密度脂蛋白(serum low-density lipoprotein,LDL)]进行研究。 方法 选取2018年1月—2019年9月我院首次收治入院并接受药物治疗前的AD患者128例(观察组)和健康体检者84例(对照组)作为研究对象。将观察组按照CDR评分,分为轻度AD组(CDR=1)、中度AD组(CDR=2)、重度AD组(CDR=3)。采用全自动生化分析仪检测所有研究对象血脂水平。 结果 观察组与对照组研究对象2组性别构成(χ2=0.716,P=0.398)、年龄(t=0.117,P=0.907)比较,差异无统计学意义(P>0.05)。与对照组比较,重度AD组患者的TG水平低于对照组(Z=2.598,P=0.009);轻中重度AD组患者TC水平均高于对照组(LSD-t=5.185,3.837,3.701,均P<0.001);中度AD组患者HDL水平低于对照组(LSD-t=3.997,P<0.001)差异均有统计学意义。轻中重组组间比较,轻度AD患者TG水平高于重度患者(Z=2.633,P=0.008),HDL水平高于中度患者(LSD-t=2.450,P=0.015);中度AD患者HDL水平低于重度患者(LSD-t=2.288,P=0.023)。血脂水平与简易智力状态检查量表(Mini-mental State Examination,MMSE)分值之间的相关性分析显示TG与MMSE分值呈正相关(r=0.287,P=0.001)。 结论 未经药物治疗的AD患者的TC及HDL水平与正常人存在差异,证实AD疾病本身会影响部分血脂水平,而中重度AD患者尤为明显。AD患者随着认知功能减退,TG水平随之下降,但与正常人比较无明显差异。      

阿尔茨海默病患者神经心理学改变与氢质子磁共振波谱相关性研究

目的 分析不同痴呆程度阿尔茨海默病（AD）患者神经心理学改变与氢质子磁共振波谱（1H-MRS）之间的相关性.方法 按AD诊断标准、临床痴呆评定量表（CDR）纳入AD患者30例,分为轻度痴呆组、中度痴呆组、重度痴呆组,每组10例.对每例AD患者进行简易智能状态检查量表（MMSE）、日常生活能力量表（ADL）、社会功能活动量表（FAQ）、WAIS数字广度测验（DST）评定.采用1H-MRS分析技术测定双侧海马区N-乙酰天门冬氨酸（NAA）/肌酸（Cr）比值和胆碱（Cho）/肌酸（Cr）比值.结果 3组之间NAA/Cr比值差异有统计学意义（P〈0.05或P〈0.01）,随着痴呆程度加重,NAA/Cr比值逐渐减低.轻度痴呆组、重度痴呆组左侧海马区NAA /Cr比值与MMSE评分及DST评分呈显著正相关（r1=0.716、r2=0.640、r3=0.717、r4=0.766,P〈0.05）;中度痴呆组右侧海马区NAA /Cr比值与MMSE评分呈显著正相关（r=0.831,P〈0.05）;3组双侧海马区Cho /Cr比值与各量表评分均无明显相关性.结论 AD患者随着病情加重海马区代谢物NAA /Cr比值逐渐减低;海马区代谢物NAA /Cr比值变化可作为AD早期诊断、病情评估及病程监测的生物学指标.     

脑低灌注触发脑内tau过度磷酸化和胆碱能神经损害

目的 探讨脑低灌注对脑内tau蛋白的过度磷酸化和胆碱能指标变化的影响.方法 40只SD大鼠随机分为低灌注组和假手术组,永久性阻断双侧颈总动脉制作脑低灌注模型;应用Y迷宫检测大鼠学习记忆能力,用免疫组化法检测大脑皮质和海马组织色氨酸404位点tau蛋白过度磷酸化(Pser404-Tau)和胆碱乙酰转移酶(ChAT)的表达,用考马斯亮蓝法检测海马组织乙酰胆碱酯酶(AChE)活性.结果 脑低灌注术后14 d和21 d,大鼠学习记忆能力明显减退,与假手术组相比差异有统计学意义(P＜0.01);大脑皮质和海马组织Pser404-Tau阳性细胞数较假手术组明显增加(P＜0.01);大脑皮质和海马组织ChAT阳性细胞计数较假手术组明显减少(P＜0.01);海马组织AChE活性较假手术组明显降低(P＜0.01).结论 脑低灌注后出现认知功能障碍,可能与脑缺血导致脑内tau蛋白过度磷酸化、损害胆碱能神经功能有关.     

不同类型脑震荡对基底前脑胆碱能神经元的影响

目的 通过免疫组织化学的方法,观察不同类型脑震荡大鼠基底前脑胆碱能神经元的影响,初步探讨脑震荡认知障碍的机制。方法 成年SD大鼠36只,复制不同损伤程度的脑震荡模型,用胆碱乙酰转移酶（ChAT）标记基底前脑的胆碱能神经细胞,光镜下计数,并捡测反映ChAT活性的荧度值。结果 单纯型、复杂型脑震荡与对照组相比,复杂型脑震荡组与单纯性脑震荡组相比,大鼠基底前脑内侧隔核、斜角带核垂直支ChAT阳性表达细胞数减少,ChAT活性降低,差异具有显著性。结论 不同类型的脑震荡基底前脑胆碱能神经元变化程度不同,这种变化可能是脑震荡后不同程度认知障碍的病理学基础。     

Endothelial progenitor cells with Alzheimer’s disease

Background  Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer’s disease (AD). Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.

Methods  A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, Tianjin Medical University. Consecutive patients with newly diagnosed AD (n=30), patients with vascular dementia (VaD, n=34), and healthy elderly control subjects with normal cognition (n=40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.

Results  There were no significant statistical differences of clinical data in AD, VaD and control groups (P >0.05). The patients with AD showed decreased CD34-positive (CD34⁺) or CD133-positive (CD133⁺) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34⁺CD133⁺ EPCs (CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P <0.05). In the patients with AD, a lower CD34⁺CD133⁺ EPCs count was independently associated with a lower Mini-Mental State Examination score (r=0.514,P=0.004). Patients with VaD also showed a significant decrease in CD34⁺CD133⁺ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than the normal control group (P <0.01). There was no significant difference of the blood flow velocity between the AD and VaD patients (P >0.05).

Conclusions  The results provided evidence that patients with AD have reduced circulating EPCs. Endothelial function is impaired in patients with AD and vascular factors have a role in the pathogenesis of AD. CD34⁺CD133⁺ EPCs may be a novel biomarker of AD dementia.

     

Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.     

中药复方962对老龄大鼠皮质胆碱乙酰转移酶和乙酰胆碱酯酶活性的影响

为研究中药复方 962胶囊对老龄大鼠皮质胆碱乙酰转移酶 (ChAT)和乙酰胆碱酯酶 (AchE)活性的影响 ,将2 2月龄和 2 4月龄Wistar大鼠分为青年对照组、老年模型组、阳性对照脑复康组 ( 0 .56g/kg)、962中剂量组 ( 0 .9g/kg)和 962大剂量组 ( 1 .8g/kg) 5组 ,分别灌胃给药 1～ 2个月后处死大鼠。用Fonnun法和羟胺比色法分别测定 5组大鼠皮质的ChAT和AchE的活性。结果 :中药复方 962大剂量 ( 1 .8g/kg)对老龄大鼠皮质ChAT活性有提高作用 (P <0 .0 5) ,但对AchE无显著影响。提示 :中药复方 962可能通过影响老龄大鼠中枢胆碱能神经系统而改善其衰老的变化     

Z-Score成像系统辅助脑血流灌注SPECT对早期阿尔茨海默病患者的诊断有较高价值

目的 利用简易Z-Score成像系统（eZIS）对脑血流灌注SPECT图像进行分析,探讨其在早期阿尔茨海默病（AD）诊断中的价值。方法 回顾性分析2018年9月~2020年9月至南方医院核医学科行脑血流灌注SPECT检查的71例受检者的临床资料,根据2011版NIA-AA标准诊断为阿尔茨海默病源性轻度认知障碍（MCI）12例,阿尔茨海默病痴呆阶段（AD）11例,无认知障碍的的健康中老年人（NC）8例。所有受检者均已行脑血流灌注SPECT显像,并应用eZIS辅助分析,获得指标值——严重程度、范围和比率。应用SPSS23.0软件比较3组间严重程度、范围、比率的差异,并分析3个指标值单项及联合分析在早期AD中诊断效能。结果（1）3组受检者间性别（P=0.58）、年龄（P=0.21）、受教育程度（P=0.88）的差异无统计学意义;AD组（P=0.00）、MCI组 （P=0.04）简易精神状态检查量表（MMSE）分数低于NC组,AD组（P=0.02）MMSE分数明显低于MCI组,差异均有统计学意义;（2）AD组的严重程度（P=0.00）、范围（P=0.00）高于MCI组,AD组、MCI组的严重程度（P=0.00、0.00）、范围（P=0.00、0.00）、比率（P=0.00、0.00）均高于NC组,且差异均有统计学意义,AD组、MCI组的比率（P=0.09）差异无统计学意义;（3）单项分析时严重程度的诊断性能（AUC=0.911）和灵敏度（87.0%）最高,联合分析时诊断性能及灵敏度均高于单项分析,其中范围、比率联合分析的诊断性能（AUC=0.948）和灵敏度（87.0%）较高。结论 eZIS辅助脑血流灌注SPECT分析在早期阿尔茨海默病诊断中有较高的应用价值。     

阿尔茨海默病患者血糖、胰岛素及胰岛素降解酶水平的研究

目的探讨阿尔茨海默病与血糖、胰岛素及胰岛素降解酶的关系,为进一步防治阿尔茨海默病提供理论依据。方法选择32例阿尔茨海默病患者(实验组)和30例正常老年人(对照组),进行简易智能状态检查量表(MMSE)及临床痴呆评定量表(CDR)评分,实验组按照CDR分为轻、中、重度组。采用酶联免疫吸附法和化学发光法分别检测其血清胰岛素降解酶(IDE)和胰岛素水平并计算胰岛素抵抗指数。结果与对照组相比,实验组血清IDE水平下降(P<0.05)。对照组中IDE水平与胰岛素、胰岛素抵抗指数之间有相关性,而实验组中无相关性。实验组空腹血糖与认知功能呈负相关(P<0.05)。轻、中、重度组患者之间血清IDE水平无统计学差异。结论胰岛素降解酶水平的下降与阿尔茨海默病的发生有一定相关性,在阿尔茨海默病患者体内胰岛素降解酶对胰岛素及胰岛素抵抗的调节可能出现障碍。     

尼莫地平联合艾地苯醌治疗血管性痴呆的临床疗效

目的：探讨尼莫地平防治脑卒中后血管性痴呆（VaD）的临床疗效。方法：将42例脑卒中患者随机分为：受试组和对照组各21例,对两组原发病均遵照神经内科诊疗指南进行常规治疗,受试组另予尼莫地平片（30mg,口服,3／日）＋艾地苯醌片（30rag,口服,3／日）,对照组单纯尼莫地平（30mg,口服,3／日）,连续给药3个月并进行智能测定,以观察两组治疗后VaD认知功能障碍的改善情况。应用修订简易精神状态量表（MMSE）、临床痴呆程度量表（CDR）和Barthe指数评定量表（BI）评价疗效。结果：与对照组比较受试组可显著提高MMSE、CDR和BI评分,差异有统计学意义（P〈0．05）。结论：艾地苯醌联合尼莫地平治疗VaD疗效优于单纯口服尼莫地平。     

阿尔茨海默病的胆碱酯酶抑制剂治疗进展

阿尔茨海默病即老年性痴呆,是一种中枢神经系统退行性疾病,发病原因尚不清楚。目前利用胆碱酯酶抑制剂提高乙酰胆碱的水平,达到治疗改善效果。本文就他克林、多奈哌齐、卡巴拉汀和加兰他敏4种胆碱酯酶抑制剂药物的研究进展进行了综述,以期对临床治疗和进一步研究提供参考。     

血管性痴呆的动物模型及其胆碱能机制研究

目的 建立血管性痴呆（ＶＤ）的运行模型,并探讨血管性痴呆认知障碍的发病机制。方法 采用持久性双侧颈总动脉法致老龄大鼠慢必离血流灌注不足,建立老大鼠血管要模型,进行数字减影血管造影（ＤＳＡ）检查、穿梭箱试验和胆碱乙酰酶（Ｃｈｏｌｉｎｅ ａｃｅｔｙｉｔｒａｎｓｆｅｒａｓｅ,ＣｈＡＴ）免疫组化测定。结果 慢性脑血流灌注不足２月后出现明显的认知功能障碍,缺血４月后更明显;海马ＣＡ１区ＣｈＡＴ免疫反应阳性神     

简易精神状态筛查联合延迟记忆和言语流畅性检查对阿尔茨海默病诊断的意义

①目的探讨简易精神状态筛查（MMSE）联合延迟记忆和言语流畅性检查对阿尔茨海默病（AD）诊断的意义,为AD的早期诊断提供依据。②方法使用MMSE、Fuid物体记忆测验（FOM）和快速词汇检测（RVR）量表测定AD患者,选择年龄、性别和文化程度相匹配的正常对照组各41例,使用临床痴呆评定量表（CDR）评估AD患者并利用判别分析和ROC曲线分析AD诊断的特异度、灵敏度和总的准确率及ROC曲线下面积。③结果AD总体认知功能在轻、中、重度阶段呈持续性明显减退趋势（MMSE分值分别为17.71±3.71、13.20±3.55、3.29±4.46）;言语流畅性功能变化趋势与总体认知功能损害相似（RVR分值分别为16.58±5.50、10.30±3.09、2.29±4.54）;延迟记忆功能在AD早期即出现衰退,在中、重度阶段均已明显衰退（FOM分值分别为9.75.±4.60、5.80±3.85、2.57±3.95）。判别分析各量表诊断AD总准确率依次为FOM〉RVR〉MMSE,特异度依次为FOM〉MMSE〉RVR,灵敏度依次为RVR〉MMSE〉FOM。而ROC曲线下面积依次为RVR〉FOM〉MMSE。④结论MMSE与FOM、RVR中1个或2个量表联合应用时,区分AD和正常对照组总的准确率均有所提高,诊断AD的特异度和敏感度也较单用任何一个认知量表明显增高。