Alzheimer病与血管性痴呆临床对照研究

Ａｌｚｈｅｉｍｅｒ病与血管性痴呆临床对照研究程瑞艳老年期痴呆越来越引起人们的关注。为了使老人安度晚年、健康长寿，我院于１９９４年９月在浙江省首先创办了老年心理康复中心。两年多来，我们中心除收治老年期精神病外，还收治老年期痴呆８０例，其中阿尔采木病（Ａ...     

载脂蛋白E基因多态性与Alzheimer病和血管性痴呆的关系

目的 探讨载脂蛋白E(ApoE)基因多态性与Alzheimer病(AD)和血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测79例AD患者(AD组)、85例VD患者(VD组)及156名健康老年人(正常对照组)ApoE基因型和等位基因频率.结果 ApoEε3/ε4基因型及ε4等位基因频率AD组分别为25.3%及17.7%,VD组分别为25.9%及20.5%,正常对照组分别为10.9%及5.7%;AD组及VD组ApoEε3/ε4基因型及ε4等位基因频率显著高于正常对照组(均P＜0.01).结论 ApoEε4等位基因可能是AD和VD共同的危险因素.     

Alzheimer病、血管性痴呆与ABO血型的关系

血型与一些疾病的相关性曾有过大量研究。在分裂症中,青春型以AB型居多,在情感性精神障碍中,双相型以O型居多。而Alzheimer病(AD)、血管性痴呆(VD)与ABO血型的关系如何,尚未见这方面报道,本研究旨在对此作一探索。     

Alzheimer病与血管性痴呆临床特点的对照研究

目的 比较Alzheimer病(AD)与血管性痴呆(VD)的临床特点。方法 通过详细收集临床资料，并用痴呆严重程度临床评定量表(CDR)、简易精神状态检查量表(MMSE)、日常生活能力量表(ADL)评定，对38例AD与30例VD患者的发病情况、行为、精神症状特点、认知功能、日常生活能力等进行比较。结果 VD患者多急性发病、呈阶梯性病程、伴有高血压和卒中史；AD患者脑电图改变主要是双额叶及双枕叶的节律改变，以θ波及δ波为主要活动，而VD患者以不对称为主要表现；抑郁、焦虑、欣快的发生率VD患者明显高于AD患者，而幻觉、妄想、饮食障碍则明显低于AD患者；时间定向、地点定向、物体命名评分AD患者明显低于VD患者，而图形描述评分高于VD患者；AD和VD患者存在着躯体生活、工具使用能力下降的不平衡，VD患者躯体生活能力下降更明显。结论 AD与VD患者的临床特点不同，发病基础、行为、精神症状、认知功能、智能障碍、日常生活能力的评价及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。     

Alzheimer病与炎症因子基因多态性关系的研究进展

最新研究认为Alzheimer病 (AD)与炎症相关 ,如损害的神经元和神经原纤维缠结 (NFT)都是炎症的刺激物 ,刺激机体产生炎症因子 ,而炎症因子的存在可能增加AD的发病风险。炎症因子的基因多态性与AD发病风险之间的关系是AD遗传学研究的热点问题 ,目前认为至少有 10种炎症因子和急性期反应物的基因多态性与AD相关[1,2 ] 。白介素 (IL) 1A、IL 1B、肿瘤坏死因子 (TNF α)、α2 巨球蛋白 (A2 M)、和α1抗糜蛋白酶 (ACT)是目前研究较多的炎症因子 ,它们在AD患者脑组织局部分泌均增多[3 ] 。研究者一般采用免疫组化分析方法来观察炎症因…     

阿尔茨海默病与血管性危险因素

阿尔茨海默病(Alzheimer disease,AD)是一种多因素致病疾病,涉及遗传、环境和社会心理等诸多方面以及不同因素之间复杂的相互作用。研究结果显示,血管性危险因素不仅与认知损害和血管性痴呆(vascular dementia,VD)有关,     

Alzheimer病和血管性痴呆患者血清β—AP与多肽生长因子相关性

目的:探讨血清β淀粉样蛋白(β－ＡＰ)和多肽生长因子含量变化及其相关性在Ａｌｚｈｅｉｍｅｒ病(ＡＤ)和血管性痴呆(ＶＤ)发病机制中的作用。方法:采用放免法检测ＡＤ患者３２例,ＶＤ患者３４例及６３例缺血性脑血管病(ＩＣＶＤ)患者血清β－ＡＰ、转化生长因子α(ＴＧＦ－α)和类胰岛素样生长因子Ⅱ(ＩＧＦ－Ⅱ)水平,与对照组比较。结果:ＡＤ与ＶＤ患者血清β－ＡＰ、ＴＧＦ－α、ＩＧＦ－Ⅱ水平明显高于ＩＣＶＤ组和对照组,有显著差异(Ｐ＜０．０１),两组患者血清β－ＡＰ和ＩＧＦ－Ⅱ之间呈明显相关关系。结论:①β－ＡＰ是ＡＤ和ＶＤ发病危险因素;②引起ＡＤ和ＶＤ神经元毒性作用进而导致痴呆与ＴＧＦ－α和ＩＧＦ－Ⅱ增多有关;③β－ＡＰ与ＴＧＦ－α、ＩＧＦ－Ⅱ密切相关,并在老年斑形成过程中起主要作用。     

Alzheimer病与血管性痴呆患者认知功能对照研究

目的探讨Alzheimer病与血管性痴呆患者认知功能状况及其之间差异。方法对36例临床诊断的Alzheimer病、35例血管性痴呆患者及35例健康人进行了事件相关电位(ERP)和简易智力状态检查(MMSE)测试。结果Alzheimer病组、血管性痴呆组ERP测定的异常率为94.4%(34/36)和85.7%(30/35),两组ERP中N2、P3波潜伏期较正常对照组延长,P3波幅降低,其差异具有统计学意义(P<0.01);而Alzheimer病组ERP测定N2、P3波潜伏期较血管性痴呆组延长,P3波幅降低,其差异具有统计学意义(P<0.05)。Alzheimer病组、血管性痴呆组MMSE量表总分值与分量表得分值较正常组降低,差异具有统计学意义(P<0.01,P<0.05);Alzheimer病组与血管性痴呆组比较,在MMSE量表总分、时间定向及物体命名等分值明显降低,差异具有统计学意义(P<0.05)。结论Alzheimer病与血管性痴呆患者均存在明显的认知功能减退,且Alzheimer病认知损害更为明显。     

Alzheimer病的环境危险因素

本文从传染、铝摄入、有机溶液、电磁场、震动及地域因素等方面介绍了Ａｌｚｈｅｉｍｅｒ病的环境危险因素。     

阿耳茨海默性痴呆与血管性痴呆的ApoE基因多态性研究

目的探讨ApoE基因在阿耳茨海默性痴呆（Alzheimer-typedementia,AD）与血管性痴呆（Vasculardementia,VD）患者当中的分布情况,以找出中国人的特点,评价ApoE基因检测在早期预测性诊断中的作用,比较AD与VD在ApoE基因多态性方面的异同。方法采用PCR-RFLP方法,对41例AD、35例VD和30例对照进行ApoE基因型测定。结果小于70岁的AD患者,其ε4等位基因频率大大高于同龄VD组患者和同龄对照组（P＜0.01和P＜0.05）。而≥70岁的AD患者ε4频率明显低于70岁以下AD患者（P＜0.01）。结论（1）ApoEε4与散发性AD之间具有明显相关性,其基因型以4/3为主,而ε4/4相对于国外文献报道要少。（2）AD组ε4等位基因频率高于VD组（P＜0.05）。（3）评价AD发病危险时,年龄因素不容忽视,70岁以下ε4携带者可能具有更高的AD发病危险性。     

阿尔茨海默病和血管性痴呆的临床症状研究

目的：了解阿尔茨海默病(AD)和血管性痴呆(VD)患者不同严重程度痴呆时临床症状。方法：认知功能测试量表采用简易智力状态检查(MMSE)、日常生活活动能力量表(ADL)，精神行为症状采用汉密尔顿抑郁量表(HAMD)、老年临床评定量表(SCAG)对住院AD157例及VD150例进行测试。结果：两组患者有不同程度的认知功能障碍及精神行为症状。AD组患者认知功能较差，VD组患者躯体生活自理较差。结论：不同严重程度的AD和VD患者临床症状有差异。     

血管内皮生长因子基因启动子区多态与散发性阿尔茨海默病的关系

目的 研究血管内皮生长因子(vascular endothelial growth factor,VEGF)基因启动子区多态与散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)发病的关系.方法 用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)或直接测序的方法对北方汉族279例SAD患者和317名健康对照者进行多态分型.采用SPSS 11.5统计学软件包进行等位基因和基因型分布的比较及其与疾病的关联分析.结果 北方汉族人群中VEGF启动子存在3个多态位点:-2578C/A(rs699947)、-2549I/D(rs35569394)和-1154G/A(rs1570360),其中-2549I/D位点为18个碱基的插入或缺失.-2578C/A和-2549I/D存在显著的连锁不平衡,当-2578为A等位基因时,-2549I/D位点有18个碱基的插入,而当-2578是C纯合子时,-2549I/D位点则为18个碱基的缺失.这3个多态位点的基因型频率、等位基因频率以及单体型分布在SAD患者和对照组间差异无统计学意义.用Logistic回归校正年龄、性别和ApoE状态后,-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的亚组中,单体型-2549D/-1154G可能增加SAD的发病风险(OR=1.325,95%CI1.023～1.716,P=0.033).结论 北方汉族人群中VEGF启动子存在3个多态位点-2578C/A、-2549I/D和-1154G/A.-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的情况下,VEGF启动子的-2549D/-1154G单体型可能是SAD发病的危险因素.     

线粒体 DNA 与阿尔茨海默病的关系

阿尔茨海默病(AD)是最常见的与痴呆有关的神经退行性疾病。已证实家族聚集性 AD与淀粉样前体蛋白基因及早老素1、早老素2基因的突变有关,而迄今为止,仍未发现与散发性 AD 相关的致病基因。研究表明,线粒体 DNA(Mitochondrial DNA,mtDNA)突变可导致能量代谢障碍、氧化应激增多以及β淀粉样蛋白的积累,进而导致 AD 的发生、发展。然而,关于 mtDNA 突变或单倍群与 AD关系的研究结果是有争议的。现对 mtDNA 与 AD 的关系进行综述,以期指导后续研究。     

Mirror writing in elderly patients with Alzheimer disease and vascular dementia

BACKGROUND: The results showed that mirror writing (MW) was correlated with the development of written language, so that MW examination may be one of methods to examine the intelligence of elderly people. OBJECTIVE: To study the MW in elderly patients with Alzheimer disease (AD) and vascular dementia (VaD) and take appropriate scale for their evaluation. DESIGN: Taking the written portion of the Chinese Aphasia Examination Scale (1994) for assessment. SETTING: Department of Neurology, Neuropsychological Laboratory, Beijing Hospital. PARTICIPANTS: From March 1998 to January 2001, 33 patients with AD, 30 patients with VaD admitted into Department of Neurology, Beijing Hospital was enrolled into study. Criteria according to the Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV), published by the American Psychiatric Association was used to diagnose AD, while criteria according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’ Enseignement en Neurosciences (NINDS-AIREN) and Alzheimer Disease Diagnostic and Treatment Center (ADDCT) were used for diagnosis of VaD. AD group contained 19 males and 14 females aged 60–83 years. Twenty-eight males and 2 females, aged 60–87 years made up the VaD group. The 63 healthy elderly subjects matched on age and education as controls were enrolled into study. The matched controls were categorized AD control (n =33) and VaD control (n =30). All patients and controls were understanding and agree with all items of assessment. METHODS: MW examination, Mini Mental State Examination (MMSE), Hachinski Ischemic Scale, the Global Deterioration Scale (GDS) were examined in all subjects. ① Use the written potion of the Chinese Aphasia examination Scale (1994), patient using MW for 91%–100% of dictation had complete MW, those using MW for 51%–90% of dictation had severe MW, those using MW for 11%–50% had moderate MW, those using MW for 1%–10% had mild MW. ② According to the MMSE, the patients were considered to have dementia if they were illiterate and had an MMSE score ≤ 17 score or educated time ≤ 6 years and MMSE ≤ 20 score or educated time > 6 years and MMSE ≤ 24 score. ③ Using the Hachinski Ischemic Scale to differentiate the AD and VaD, it included 6 items and total 9 scores. > 7 score was VaD, < 4 score was AD and 4–7 score was blended dementia. ④ Using the GDS to assess cognitive function: Standard criteria were divided in 7 degrees: 1 degree: no impairment of cognition and 7 degree: very severe impairment of cognition. MAIN OUTCOME MEASURES: The data of MW examination, evaluation of MMSE, Hachinski Ischemic Scale and the GDS of all assessed subjects. RESULTS: All 63 cases of AD and VaD and 63 healthy controls were entered for analysis. ①Results of MW examination: A total of 17 patients with AD were characterized as using MW, 3 with moderate MW and 14 patients with mild MW. In the corresponding control group, only 2 subjects were characterized as being mild MW. The VaD group has 23 patients with MW, 2 with moderate and 21 patients with mild MW. ② MMSE score: MMSE score of AD group was much lower than that of individuals in control group [(20.15±3.40), (29.73±0.40) score, P < 0.01], MMSE score of VaD group was much lower than that of individuals in control group [(19.33±2.75), (29.12±0.63) score, P < 0.01]. ③ Hachinski Ischemic Scale and GDS score: Rating according to the Hachinski Ischemic Scale was higher in VaD patients compared to AD patients [(9.61±1.69), (1.09±0.60) score, P < 0.01]. The GDS score did not significantly differ between the AD group and the VaD group. CONCLUSION: ① MW examination could be used as an indicator of intelligence in healthy elderly people and also could be used as one of methods to assess the intelligence in AD and VaD patients. ② Grade of severity of MW may indirectly reflect the degree of dementia.     

β-分泌酶2多态性位点rs2252576与散发性阿尔茨海默病的相关性分析

目的 研究β-分泌酶2（BACE2） rs2252576位点基因多态性与中国北方汉族人群散发性阿尔茨海默病（SAD）发病的相关性.方法 随机选取10例SAD患者和10名健康对照者进行BACE2外显子区测序.筛查出第5外显子上游10bp存在一多态性位点rs2252576C/T,随后对348例SAD患者和294名健康对照者进行多态性分型及统计学分析.结果 SAD患者和健康对照组的BACE2基因rs2252576多态性位点基因型和等位基因频率差异无统计学意义（P＞0.05）.根据是否携带ApoEε4等位基因进行进一步分层比较后,该位点差异仍无统计学意义（P＞0.05）.应用Logistic回归分析平衡了年龄、性别和ApoE分型的影响后,差异仍无统计学意义（P＞0.05）.结论 中国北方汉族人群中BACE2基因rs2252576 C/T位点的基因多态性与SAD的发病可能无关.     

血管性痴呆与阿尔茨海默病的临床对照研究

目的了解血管性痴呆（VD）与阿尔茨海默病（AD）的临床不同特征。方法以CCMD--3为诊断标准，参照ICD-10，对符合标准的36例VD患者，31例AD患者进行对照分析，长谷川痴呆量表（HDS）及自编问卷进行评定。结果VD与AD的起病形式及病程发展不同，在年龄、性别、病程等无统计学差异的情况下，AD重于VD，两病在轻、中度阶段经治疗可有好转或减轻，在重度期精神症状治疗无显著差异。结论重视疾病的早期诊断，抓住治疗时机，可延缓和减少疾病恶化及并发症发生。     

Paternal age is a risk factor for Alzheimer disease in the absence of a major gene

We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E ε  4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7±8.1 years) than fathers of both other groups (high MGAD probability 31.3±6.9 years, P =0.004; controls 32.6±6.8 years, P =0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition. Received: February 23, 1998 / Revised and Accepted: May 20, 1998     

阿尔茨海默病载脂蛋白E基因多态性研究

目的：探讨载脂蛋白E(APoE)基因与阿尔茨海默病(AD)的行为和精神症状之间的关系。方法：采用聚合酶链式反应(PCR)扩增技术和限制性片段长度多态性(RFLP)技术测定85例AD病人的APOE基因多态性；采用AD病理行为量表评定病人的行为和精神症状。结果：对各等位基因及基因型频率分布在有无某项痴呆的行为和精神症状(BPSD)之间进行比较，发现具有行为紊乱症状的病人的ε2等位基因频率分布显著高于无行为紊乱症状的病人；无焦虑和恐惧病人的ε2等位基因频率分布显著高于有症状的病人。AD病人伴有BPSD症状及其严重程度，各基因型之间差异均无显著性。结论：ε2等位基因可能与行为紊乱、焦虑和恐惧症状有一定关联，而APoE基因与阿尔茨海默病的其它行为和精神症状之间未发现关联。     

帕罗西汀治疗阿尔茨海默病的抑郁对照研究

目的：比较帕罗西汀与氯米帕明在阿尔茨海默病(AD)抑郁症状治疗中的疗效和不良反应。方法：帕罗西汀组51例，氯米帕明组44例，均诊断为AD，汉密顿抑郁量表(HAMD，17项)≥18分。比较两组患者治疗后的HAMD减分率，采用副反应量表(TESS)评定不良反应。结果：帕罗西汀组与氯米帕明组总体疗效相当，但帕罗西汀组起效较快，不良反应发生率低。结论：帕罗西汀在AD抑郁症状治疗中具有一定优势，值得临床推广应用。     

脑血管病变与阿尔茨海默病关系的病例对照研究

目的探讨阿尔茨海默病与经头部CT证实的脑血管病变、白质病变的可能关系。方法选择60例阿尔茨海默病患者及84例年龄、性别与之相匹配的认知功能正常老年人,采用盲法分析临床诊断前3～5年的头部CT资料,调查头部CT显示的各种脑血管病变;对白质病变进行分区评分(评分等级为0～3分),并将双侧额区、顶枕区、颞区及幕下共8个区域的总和作为白质病变总评分;测量钩间距、双侧侧裂宽度、第三脑室宽度、哈氏值、脑室指数和侧脑室体部指数,以反映脑萎缩和脑室扩大的程度。结果CT资料显示,阿尔茨海默病组患者存在明显的脑血管病变、白质病变、脑萎缩和脑室系统扩大;正常对照组有脑血管病变者15例(17.86%),阿尔茨海默病组33例(55.00%),单因素分析组间差异有高度统计学意义(P=0.0001)。两组白质病变均以双侧额区和顶枕区评分居高,双侧颞区和幕下评分较低;白质病变总评分、双侧额区及左侧顶枕区白质病变评分,组间差异有统计学意义(P<0.05)。两组钩间距、双侧侧裂宽度、第三脑室宽度及侧脑室体部指数,组间差异亦有统计学意义(P<0.05);但哈氏值、脑室指数,组间差异无统计学意义(P>0.05)。多因素分析显示,考虑白质病变总评分时,脑血管病变、第三脑室宽度和钩间距与阿尔茨海默病有关(OR=3.222,1.507,1.271;95%CI:1.199～8.689,1.197～1.897和1.093～1.476);考虑不同部位白质病变评分时,脑血管病变、左侧额区白质病变评分、第三脑室宽度和钩间距与阿尔茨海默病有关(OR=2.876,1.744,1.548和1.268;95%CI:1.048～7.895,1.021～2.978,1.221～1.962和1.091～1.473);其中第三脑室宽度和钩间距OR值变化不明显。双侧侧裂宽度和侧脑室体部指数与阿尔茨海默病无关。剔除年龄和脑萎缩等影响因素后,多因素分析显示脑血管病变、左侧额区白质病变评分与阿尔茨海默病显著相关。结论阿尔茨海默病患者的脑血管病变和白质病变均可能促进阿尔茨海默病的发生和发展。控制脑血管疾病,减轻白质病变程度,将有助于阿尔茨海默病的防治。