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。     

社区阿尔茨海默病早期征象的研究

目的　了解阿尔茨海默病 (AD)患者的早期征象。方法　在 1997年 6月至 1998年 4月对成都市 5 35 3名年龄≥ 5 5周岁的社区人群进行痴呆患病率调查的基础上 ,于 2 0 0 0年 11月 12日至2 0 0 1年 3月 2 1日仍用两阶段法随访其中的 36 87名正常人群。实际随访 2 86 9名 (77 81% ) ,失访 818名 (2 2 19% )。用美国精神障碍诊断与统计手册第 3版修订本的标准诊断痴呆 ,用美国神经病语言障碍和卒中研究所及阿尔茨海默病与相关障碍协会的AD标准做出可能AD和很可能AD诊断 ,用临床痴呆程度评定量表评定痴呆严重程度。结果　 (1)查出可疑痴呆 5 8例 (2 0 4 % ) ,AD2 5例 (0 88% )。(2 )AD患者年龄 [(79± 6 )岁 ]高于可疑痴呆者 [(76± 8)岁 ]和正常人 [(6 6± 7)岁 ;P <0 0 0 1]。(3)AD患者基线简易精神状态检查 (MMSE)总分及各分项评分均低于可疑痴呆者和正常人 ,均P <0 0 0 1。AD患者随访时的MMSE总分和积木测验评分下降了 [(6 86± 5 77)分和 (4 11± 6 4 1)分 ],下降程度快于可疑痴呆者 [(3 5 5± 4 5 0 )分和 (4 89± 6 89)分 ]和正常人 [(0 5 6± 3 76 )分和 (1 11± 6 86 )分 ;P <0 0 5 ]。有记忆力减退病史者 (2 83例 )中 ,AD患者的比例 (44 0 % )显著高于可疑痴呆者 (32 8% )和正常人 (9     

帕金森病患者基础PRL水平与并发痴呆及抑郁关系的研究

目的探讨帕金森病(PD)患者基础血浆泌乳素(prolactin,PRL)水平及与PD伴随的痴呆及抑郁的关系。方法测定167名在我院体检的正常老人(正常对照组)及113例PD患者(PD组)基础血浆PRL水平,并采用汉密顿抑郁量表(HAMD)、简明智能状况评价量表(MMSE)把PD患者分别划为痴呆组和非痴呆组及伴发抑郁组和非抑郁组,同时筛选同期我科收治的阿尔茨海默病(AD)患者20例及心理门诊治疗的功能性抑郁症患者50例(功能性抑郁组)。分别比较各组的PRL水平。结果PD组者的基础血浆PRL平均水平为(9.44±4.07)μg/L,与正常对照组[(9.76±3.97)μg/L]比较无统计学差异;PD伴发抑郁组平均PRL水平为(8.75±4.12)μg/L,与PD非抑郁组[(10.52±3.97)μg/L]、功能性抑郁组[(9.52±5.17)μg/L]比较均无统计学差异;PD伴发痴呆组平均PRL水平为[(5.26±4.90)μg/L],明显低于PD非痴呆组[(10.19±5.19)μg/L]及AD组[(7.85±4.25)μg/L]。结论PD患者出现痴呆时其基础血浆PRL水平降低。PD患者可能有DA、Ach、5HT能神经递质平衡的紊乱。     

住院老年痴呆患者的病情严重程度及其有关因素分析

目的了解住院老年痴呆患者的病情严重程度及其影响因素.方法76例住院痴呆患者,其中AD42例,MID34例,平均年龄(75.89±8.04)岁,平均病程(4.94±3.15)年,平均住院时间(2.27±2.06)年,评定工具为MMSE、ADL、ADSS、SBS和PANSS.结果不同性别和文化程度的中晚期痴呆患者的认知功能,日常生活能力无显著差异,AD和MID之间各量表分也元差异(P＞0.05),痴呆程度较重的患者异常行为和锥体外系征发生率及程度均较高(P＞0.05).结论AD和MID至后期痴呆时已无临床差异,不同性别、不同文化程度对中晚期痴呆严重程度的影响不大.但男性、文化程度低、PANSS、RSESE分高的患者痴呆发展速度较快.     

阿尔茨海默病患者红细胞超氧化物歧化酶与载脂蛋白ε_4等位基因的相互关系

目的　探讨阿尔茨海默病 (AD)患者的外周血氧化应激与载脂蛋白 (apo)Eε4 等位基因的相互关系。方法　分别测定 2 5例散发性AD患者 (AD组 )、2 0例血管性痴呆 (VD)患者、2 2名正常人(正常组 )的红细胞超氧化物歧化酶 (SOD)、血浆一氧化氮 (NO)浓度及apoE等位基因频率。结果　AD组的SOD活性 [U /mg血红蛋白 ]为 10 80± 35 1,明显高于正常组 [(818± 330 )U],P <0 0 5 ;NO浓度的差异无显著性。根据apoEε4 等位基因进行分层后 ,不携带ε4 组间SOD活性差异有显著性 ,AD组高于正常组 (P <0 0 5 )。AD患者的SOD活性与临床痴呆分级量表 (CDR)呈显著性负相关 (r =- 0 480 ,P <0 0 5 ) ,与BLESSED痴呆量表分呈显著性负相关 (r =- 0 5 2 2 ,P <0 0 1) ,正常组的SOD活性与年龄呈显著性负相关 (r=- 0 430 ,P <0 0 5 )。结论　与痴呆严重程度有关的氧化应激可能参与AD患者的病理生理变化 ,并可能受ε4 等位基因的影响     

阿尔茨海默病患者红细胞超氧化物歧化酶与载脂蛋白ε4等位基因的相互关系

目的探讨阿尔茨海默病(AD)患者的外周血氧化应激与载脂蛋白(apo)Eε4等位基因的相互关系.方法分别测定25例散发性AD患者(AD组)、20例血管性痴呆(VD)患者、22名正常人(正常组)的红细胞超氧化物歧化酶(SOD)、血浆一氧化氮(NO)浓度及apoE等位基因频率.结果AD组的SOD活性[U/mg血红蛋白]为1080±351,明显高于正常组[(818±330)U],P＜0.05;NO浓度的差异无显著性.根据apoEε4等位基因进行分层后,不携带ε4组间SOD活性差异有显著性,AD组高于正常组(P＜0.05).AD患者的SOD活性与临床痴呆分级量表(CDR)呈显著性负相关(r=-0.480,P＜0.05),与BLESSED痴呆量表分呈显著性负相关(r=-0.522,P＜0.01),正常组的SOD活性与年龄呈显著性负相关(r=-0.430,P＜0.05).结论与痴呆严重程度有关的氧化应激可能参与AD患者的病理生理变化,并可能受ε4等位基因的影响.     

阿尔茨海默病患者血浆基质金属蛋白酶-3水平的对照研究

目的探讨阿尔茨海默病(AD)患者血浆基质金属蛋白酶-3(MMP-3)水平的变化。方法应用双抗体夹心酶联免疫法测定30例AD患者(AD组)、27例血管性痴呆(VD,VD组)患者及26名正常对照者(正常人组)的血浆MMP-3水平。根据简易精神状况检查量表(MMSE)评分将AD患者分为重度组(MMSE≤10分,8例)、中度组(MMSE>10分~≤20分,12例)和轻度组(MMSE>20分~<24分,10例)。血浆MMP-3水平采用方差分析进行统计学比较。结果AD组血浆MMP-3水平为(5.8±1.2)×104U/L,VD组为(5.3±0.8)×104U/L,正常人组为(4.8±0.8)×104U/L。AD组高于正常人组(P<0.001)及VD组(P<0.05),VD组亦高于正常人组(P<0.05)。AD重度组血浆MMP-3水平[(6.8±1.3)×104U/L]分别高于AD轻度组[(5.5±1.0)×104U/L]及AD中度组[(5.6±1.0)×104U/L],P均<0.05。AD组MMP-3水平与MMSE评分呈显著负相关(r=-0.450,P<0.05)。结论血浆MMP-3水平与AD严重程度相关;其水平增高可能与AD发病过程有关,其差异对AD与VD的鉴别可能有辅助价值。     

简易智能精神状态检查量表检测老年期痴呆患者的应用探讨

目的 研究简易智能精神状态检查量表(mini-mental state examination。MMSE)的人群分布特征、临床适用性、痴呆筛查的界定值及痴呆早中期的分界值。方法 采用随机分层抽样方式。对北京城乡40岁及以上常模、痴呆及易混淆疾病人群进行MMSE调查研究及统计分析。结果 MMSE检测结果表明．在城乡常模人群间差异有显著性。其分值随年龄增长而下降．文化程度越高分值越高；痴呆筛查的界定值文盲组≤24分、文化组(初小及以上)≤26分．痴呆早中期分界值文盲组为17分、文化组(初小及以上)为19分。结论 MMSE涵盖的认知项目广泛。操作简单方便。筛查痴呆敏感度较高。适于临床广泛应用，但MMSE判断的认知功能下降是非特异性的．受许多疾病及意识、精神状态干扰，故应结合临床综合判断。     

阿尔采默病和血管性痴呆死亡病例病程分析

目的 分析住院老年痴呆患者起病年龄,死亡年龄及病程。方法 对住院87例痴呆患者起病年龄,死亡年龄,病程进行统计分析,并对阿尔采默病(AD)与血管性痴呆(VD)组间及组内进行对照。结果 AD的起病年龄高于VD(P<0.01),AD的平均死亡年龄大于VD(P值<0.01),AD组的平均病程为(4.0±2.7)年,VD组的平均病程为(4.6±3.8)年,AD与VD的病程无明显差异(P>0.05),AD平均病程女性大于男性(P<0.05),男性平均(3.3±2.1)年,女性(5.3±3.1)年。结论 女性AD的生存时间明显长于男性,AD病人与VD病人存在不同的死亡影响因素。     

单纯脑白质疏松症与皮质下动脉硬化性脑病患者记忆障碍的对比研究

目的比较单纯脑白质疏松症(LA)与皮质下动脉硬化性脑病(SAE)患者记忆障碍的特征。方法采用临床记忆量表对单纯LA、SAE患者各30例进行记忆功能检测及简易精神状态量表(MMSE)检测,并与30名健康老年人比较。结果单纯LA组患者各项记忆量表成绩及记忆商(MQ)均明显低于健康对照组(均P<0.01),其中图像自由回忆(12±5)、人像特点联系回忆(16±5)下降明显;单纯LA组各项记忆量表成绩及MQ均高于SAE组(P<0.05～0.01),其中SAE组患者指向记忆(10±7)、联想学习(14±5)明显下降;单纯LA组无痴呆发生,SAE组22例MMSE≤19分,痴呆发生率73.33%;MQ>70的患者痴呆发生率明显低于MQ≤69的患者(P<0.01)。结论(1)单纯LA组患者有明显记忆障碍,但程度明显轻于SAE患者;(2)单纯LA组患者无痴呆发生,SAE组痴呆发生率高,且与记忆损害程度成正比。     

视频脑电图在小儿癫痫诊断中的应用

目的评价视频脑电图(video-EEG)在小儿癫诊断中的应用价值。方法对126例具有发作性症状的患儿进行连续8h的包括清醒、睡眠、诱发试验及必要的认知测验的视频脑电图监测。结果经发作期视频脑电图证实,39例初诊为癫性发作的患儿中14例(35%)为非癫性发作;15例其他症状发作中13例(86%)为非癫性发作。64例样放电患儿中51例(80%)确定发作类型,22例(34%)确定癫类型。视频脑电图可发现短暂轻微的癫发作及样放电引起的一过性认知损伤。结论视频脑电图在排除非癫性发作、确定癫性发作的类型、评价脑电-临床关系方面可提供准确可靠的证据,进一步提高癫的临床诊断水平。     

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltage-dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia-ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.     

脑电图预测痫性发作研究进展

癫痫(epilepsy)是由脑部神经元高度同步化异常放电所致的临床综合征,系神经系统的常见病,困扰着全世界约1%的人群.每次神经元的阵发性放电或短暂的脑功能异常称为痫性发作(seizures).     

Storage of lipofuscin in neurons in mucopolysaccharidosis

Summary A histochemical and ultrastructural study was made on the brain of a 23-year-old man with Sanfilippo's syndrome. In accordance with previous reports the cortical nerve cells contained a PAS-positive lipid storage substance. This showed intense autofluorescence in UV-light and was positive with various stains for lipofuscin. The storage material appeared ultrastructurally as inclusion bodies composed of short lamellated membranes, granular material, and vacuoles. In addition, concentrically and transversely lamellated membranous cytoplasmic bodies were observed in the nerve cells. It is concluded that the PAS-positive lipid storage material in the neurons was composed partly of lipofuscin in addition to other lipids presumably glycosphingolipids.Supported by a grant from the Expressen Prenatal Research Foundation     

Role of vincristine in the inhibition of angiogenesis in glioblastoma

Objective: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α).

Methods: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O₂ (hypoxia).

Results: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G₂-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC₅₀), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels.

Conclusions: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.     

自噬参与帕金森病发病的研究进展

近年来,蛋白质的降解障碍被认为是帕金森病（Parkinson’Sdisease,PD）发病过程中的重要因素,人们已经公认泛素一蛋白酶体系统（ubiquitin--pro—teasomesystem,UPS）功能异常或衰竭能够导致细胞内异常蛋白蓄积、细胞功能障碍,甚至细胞凋亡。与此同时,蛋白降解的另一条途径——自噬-溶酶体途径（autophagy—lysosomepathway,ALP）也已成为了生命科学领域的研究热点,自噬与神经变性疾病,尤其是PD的关系日益受到人们的重视。     

Midazolam in treatment of various types of seizures in children

Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8±1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Issues in evaluation of cognition in the elderly in developing countries

Background:

Developing regions of the world host the majority of elderly subjects who are at risk for dementia. Reliable epidemiological data from these countries is invaluable in tackling this global problem. Scarcity of such data in literature is largely attributable to problems that are unique to developing communities worldwide.

Objective:

To classify and describe the problems that interfere with the collection of reliable epidemiological data on cognitive impairment in the elderly in developing communities, and to suggest practical solutions for some of them.

Methods:

Inferring from the experiences of a large, ongoing, population-based study on the cognitive impairments in the elderly in South India and from the review of literature.

Conclusion:

A fatalistic attitude regarding aging in the communities, significant heterogeneity in educational abilities and activities of daily living, high illiteracy among rural subjects, and lack of an organized health care system and updated demographic figures are some of the major factors that contribute to technical, namely, methodology-related problems and practical, namely, subject-related problems in such epidemiological studies.