Chinese patients with Lewy body dementia had shorter survival and developed complications earlier than those with Alzheimer’s disease

INTRODUCTIONAlzheimer’s disease (AD) and Lewy body dementia (LBD) are two common forms of dementia. There are still controversies regarding whether LBD patients have a worse clinical course than AD patients.METHODSWe retrospectively reviewed all biomarkers that supported AD and LBD patients presenting to the Memory Clinic of Queen Mary Hospital, Hong Kong, between 1 January 2008 and 30 December 2016. Diagnoses of AD and LBD were supported by clinical diagnostic criteria and biomarkers. LBD patients included those with dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Baseline demographics, presenting clinical features, degree of cognitive impairment and specified clinical outcomes were compared.RESULTSWe recruited 31 AD and 25 LBD patients (18 DLB, 7 PDD). When measured from disease onset, LBD patients were noted to have shorter overall survival (p = 0.02) with earlier occurrence of falls (p < 0.001), dysphagia (p < 0.001), pneumonia (p = 0.01), pressure injuries (p = 0.003) and institutionalisation (p = 0.03) than AD patients. Cox regression analyses showed that LBD predicted falls (hazard ratio [HR] 5.86, 95% confidence interval [CI] 2.29–15.01, p < 0.001), dysphagia (HR 10.06, 95% CI 2.50–40.44, p = 0.001), pressure injuries (HR 17.39, 95% CI 1.51–200.10, p = 0.02), institutionalisation (HR 2.72, 95% CI 1.12–6.60, p = 0.03) and death (HR 2.96, 95% CI 1.18–7.42, p = 0.02).CONCLUSIONLBD patients had shorter overall survival with earlier occurrence of pre-specified long-term events compared with AD patients. LBD also independently predicted pre-specified long-term events.     

载脂蛋白E基因多态性与阿尔茨海默病和帕金森病痴呆作用关系的研究

目的 探讨阿尔茨海默病（ＡＤ）、帕金森病（ＰＤ）、帕金森病痴呆（ＰＤＤ）的发病机制及与载脂蛋白Ｅ（ＡｐｏＥ）基因多态性的关系。方法 对ＡＤ组（４８例）、ＰＤ组（５４例）、ＰＤＤ组（４３例）和非痴呆对照组（２３４例）的ＡｐｏＥ基因频率及基因型分布进行对照研究。结果 ＡＤ组ＡｐｏＥε４基因频率明显升高（２１．９％）,显著高于非痴呆对照组（５．１％,Ｐ〈０．０１）,表明ε４与ＡＤ发病关系极为密切。ＰＤ和     

Takotsubo cardiomyopathy in a bedridden patient with dementia and communication difficulties due to Alzheimer’s disease

Takotsubo cardiomyopathy is a transient wall motion abnormality of the left ventricular apex, accompanied by emotional or physical stress. Although Takotsubo cardiomyopathy is generally considered a benign disease, severe clinical complications may occur, and early detection of the disease is important. In this report, we present the case of an 86-year-old bedridden woman with a history of bronchial asthma who was transferred to our hospital because of wheezing. She was diagnosed with Alzheimer’s disease and had communication difficulties. After an asthma attack and improvement, Takotsubo cardiomyopathy was identified via electrocardiography. She was unable to complain of any symptoms but showed serial electrocardiographic changes, elevated myocardial markers, and transient left ventricular apical ballooning. The prevalence of dementia increases dramatically with age. This case indicates that Takotsubo cardiomyopathy may occur even in patients with severe dementia, who are bedridden and show communication difficulties in a clinical setting.     

阿尔茨海默病与血管性痴呆患者合并症的比较

目的:比较阿尔茨海默病(Alzheimer's disease,AD)与血管性痴呆(vascuiar dementia,Va D)患者合并症的差异。方法:收集46例老年期痴呆患者,分为阿尔茨海默病患者组(AD组)22例,血管性痴呆患者组(Va D组)24例,了解两组患者的合并症发生率,并进行分析。结果:高血压的发生率在Va D组患者显著高于AD组,而糖尿病、冠心病、慢性阻塞性肺疾病、高脂血症、贫血的发生率,在两组患者之间均无显著差异。结论:高血压可能在Va D患者的病程中起重要作用,糖尿病、冠心病、慢性阻塞性肺疾病、高脂血症、贫血患者伴随着部分AD和Va D的发生、发展过程,对各种因素的干预,可能对老年期痴呆患者的防治和预后均有意义。     

头颅CT平扫在鉴别老年阿尔茨海默病与血管性痴呆患者中的临床应用

目的探讨头颅CT平扫在老年阿尔茨海默病(AD)和血管性痴呆(VD)患者鉴别诊断中的应用价值。方法选取2019年1月至2020年1月合肥市滨湖医院老年科收治的101例痴呆患者,其中55例阿尔茨海默病者作为AD组,46例血管性痴呆患者作为VD组,比较分析两组患者头颅CT检查结果。结果AD组大脑半球最大横径、大脑半球最大横径与侧脑室最大宽度比值小于VD组,AD组外侧裂池最大宽度大于VD组,差异有统计学意义(P<0.05)。VD组腔隙性脑梗死和大面积脑梗死/出血灶的发生率明显高于AD组,AD组侧脑室颞角扩大发生率高于VD组,差异有统计学意义(P<0.05)。结论头颅CT平扫在鉴别老年患者阿尔茨海默病和血管性痴呆方面具有较高的临床应用价值。     

阿尔茨海默病的药物治疗新进展

近年来,随着以β淀粉样蛋白（β-Amyloid,Aβ）单抗为代表的疾病修饰治疗（disease-modifying therapies,DMT）药物的出现,阿尔茨海默病（Alzheimer''s disease,AD）的药物治疗进入了一个全新的阶段,目前已经有2种靶向淀粉样蛋白的抗体-阿杜卡单抗和伦卡纳单抗相继上市,在全世界引起了广泛关注;同时非Aβ非tau蛋白治疗靶点的药物研发也取得明显进展。本文拟对AD新型药物的研发和应用,包括临床试验阶段和已获批上市的药物治疗进展进行一全面分析和阐述。     

阿尔茨海默病、脑血管性痴呆及正常老人的事件相关电位研究

目的：探讨事件相关电位对阿尔茨海默病（AD）的脑血管性痴呆（VD）的临床应用价值。方法：检测了25例AD患者,24例VD患者和22名正常老年人（NC）的事件相关电位。结果：VD组命令信号后负变化（PINV）出现率增多（VD组79％,NC组32％,X2值10．47,P＜0．01）,与NC组相比,VD组CNV早成分M1,晚成分M2潜伏期延长,反应时间延迟,且与其认知功能评定（MMSE评分）相关。VD组早成分M1波幅下降（P＜0．01）,与NC相比,AD组和VD组P300均有多指标变异,且为同一方向即潜伏期延迟和波幅下降,但变异程度AD组更趋明显,与VD组相比,AD组在Ca区域,靶P2,N2潜伏期上延迟,靶P2波幅一降,结论：这些改变与其认知功能评定（MMSE评分）相关,分析P300的不同成分可能对鉴别AD和VD类型有意义。ERP是评定老年痴呆如患者大脑综合功能的辅助工具之一,在临床上值得进一步推广应用。     

阿尔茨海默病和额颞叶痴呆患者徘徊行为落日现象的比较分析

目的 探索阿尔茨海默病和额颞叶痴呆患者徘徊行为的落日现象,并比较该现象在两痴呆亚型之间的差异.方法 利用电子示踪监测系统对2008年9月至2009年9月入住大阪浅香山医院,符合纳入标准的27例阿尔茨海默病及7例额颞叶痴呆患者进行连续30 d的步行活动监测,分析并比较两者24h标准化活动水平的变化.结果 经Huynh-Feldt Epsilon(H-F)校正后的重复测量方差分析显示两组24h标准化活动水平差异无统计学意义(F=3.74,P=0.06),分组因素与时间因素无交互效应(F=1.42,P＞0.05),两组间标准化活动水平变化趋势不服从第17次项曲线(F=5.24,P＜0.05)和第9次项曲线(F=4.26,P=0.05).两组标准化活动水平均逐渐增高,阿尔茨海默病组在18:00达到最高点,额颢叶痴呆组则在19:00达到最高点,Bonferroni法多重比较显示阿尔茨海默病组在5:00 ～7:00的标准化活动水平较额颞叶痴呆组高(分别为0.75±0.08比0.35±0.16,F =4.91;1.13±0.13比0.49±0.26,F=5.06;1.24±0.15比0.56±0.28,F=4.47;P＜0.05),而在16:00则较低(1.65±0.11比2.22±0.22,P＜0.05).圆形分布x2检验显示额颞叶痴呆组活动峰值时间较阿尔茨海默病组延迟(14:12±5:12比15:47±4:19,x2=87.31,P＜0.01).结论 徘徊行为的落日现象在阿尔茨海默病及额颞叶痴呆中均有出现,但两者徘徊行为时间趋势不尽相同.与额颞叶痴呆患者相比,阿尔茨海默病患者徘徊行为时相较长,且峰值时间较早.     

阿尔兹海默病与血管性痴呆的诊疗对比

目的：探讨阿尔兹海默病与血管性痴呆的诊断方法和治疗效果。方法：选取我院2006～2010年收治的阿尔兹海默病和血管性痴呆患者,观察比较其诊断指标和治疗效果。结果：AD和VaD患者MMSE-R评分无显著差异;AD组和VaD组脑电图异常率有统计学意义（P〈0.01）,AD组脑电图异常率低于VaD组;AD与VaD组患者血浆Hcy、VitB12和ChE差异有统计学意义（P〈0.05）;AD组与VaD组认知功能、记忆功能和社会行为能力改善比较差异有统计学意义（P〈0.05）,VaD组改善均好于AD组。结论：通过临床症状和生化检查在一定程度上能够鉴别AD和VaD患者,同时针对二者不同的病因和发病机制,采取相应的治疗措施有一定的效果,值得临床借鉴。     

嗅觉障碍与帕金森病痴呆研究进展

<正>帕金森病(parkinson's disease,PD)是一种以运动障碍为特征的神经系统变性疾病,主要患病群体为老年人群。目前PD的运动症状治疗方案日趋完善,而PD的非运动症状愈来愈受到关注,帕金森病痴呆(parkinson's disease with dementia,PDD)是PD患者最易发生的非运动症状,研究显示,PD患者的晚期阶段,约80%的患者会进展为痴呆,这将导致更高的病死率及耗费高额的医疗成本[1]。PDD在疾病的早期阶段很难进行预测,最新调查发现嗅觉功能相关的脑区与认知障碍存在联系,严重的嗅觉障碍可     

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.     

美金刚联合脑电磁治疗阿尔茨海默病痴呆的行为精神症状的疗效观察

目的 探讨美金刚联合脑电磁治疗阿尔茨海默病(AD)痴呆的行为精神症状(BPSD)的研究.方法 选取2017年1月—2020年1月在浙江省人民医院就诊的AD伴BPSD患者122例,按照随机表法分为观察组和对照组,各61例.对照组口服美金刚片;观察组在对照组基础上结合脑电磁治疗.两组疗程均为12周.比较两组疗效,以及治疗前...     

帕金森病与痴呆

为探讨帕金森病痴呆的发生率和痴呆的类型，对３０例患者和２６例正常人进行神经心理测验。结果表明：ＨＲＢ（Ａ）－ＲＣ测验脑损伤指数（ＤＱ）为６３．６４％脑损害。ＷＡＩＳ－ＲＣ及ＷＭＳ测验智力商数（ＩＱ）、记忆商数（ＭＱ）分别为２０％和６０％轻至极重度损害。６例（２０％）符合痴呆诊断，其中皮质下痴呆４例，混合性痴呆２例。讨论了病程与痴呆的关系；指出应早期发现智能障碍，早期治疗，以利于预防或延缓痴呆的发生。     

老年性痴呆与血管性痴呆脑电图的对比分析

目的探索脑电图(EEG)对老年期痴呆诊断和鉴别诊断的价值.方法对113例阿尔茨海默病(AD)和87例血管性痴呆(VD)的脑电图进行对比分析.结果AD阳性率82.30%,VD89.66%,EEG异常与病期和痴呆严重度有关,与年龄无关,这在VD表现较为明显,而且VD可有局灶性改变.结论EEG可作为AD和VD的鉴别参考,并对鉴别痴呆与假性痴呆有实用价值.     

白细胞介素6基因敲除对阿尔茨海默病5×FAD模型小鼠β淀粉样蛋白沉积和认知的影响

目的 探讨白细胞介素6(IL-6)基因敲除对阿尔茨海默病5×FAD转基因小鼠认知及脑组织病理变化的影响。方法 IL-6^+/-小鼠与5×FAD小鼠杂交,构建5×FAD;IL-6^-/-小鼠模型,并选用3、10月龄子代小鼠进行实验。采用行为学实验对小鼠的认知记忆功能进行分析;采用HE染色和β淀粉样蛋白(Aβ)免疫组织化学染色检测小鼠脑组织病理变化。结果 得到5×FAD;IL-6^-/-模型小鼠(3月龄n=20,10月龄n=5)及5×FAD同窝对照小鼠(3月龄n=26,10月龄n=24),子代小鼠数量符合孟德尔定律。新物体识别实验结果显示,与同月龄5×FAD小鼠相比,3月龄5×FAD;IL-6^-/-小鼠的探索指数显著升高,差异有统计学意义(q=3.890,P=0.002)。Morris水迷宫空间探索结果显示,与同月龄5×FAD小鼠相比,3月龄5×FAD;IL-6^-/-小鼠目标象限停留时间及穿台次数增加,差异有统计学意义(q=3.797,P=0.012;q=2.505,P=0.017)。免疫组织化学染色结果显示,IL-6基因敲除显著减少3、10月龄5×FAD小鼠海马(q=13.490,P=0.002;q=45.680,P<0.001)及皮层(q=16.830,P=0.001;q=14.180,P=0.001)的Aβ沉积,差异有统计学意义。结论 IL-6基因敲除可明显改善阿尔茨海默病5×FAD模型小鼠的空间记忆能力,减少小鼠大脑Aβ沉积。     

Vascular disease burden in Indian subjects with vascular dementia

Background

Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia.

Aims

To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia.

Methods

In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis.

Results

Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001).

Conclusion

People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.     

TXNIP介导的氧化应激在雌激素延缓阿尔兹海默病中的作用

目的：研究硫氧还蛋白相互作用蛋白(thioredoxin-interacting protein,TXNIP)在阿尔茨海默病(Alzheimer’s disease,AD)发病及雌激素延缓AD发生中的作用。方法：检测雌二醇(E2)处理的AD细胞模型中活性氧(reactive oxygen species,ROS)和TXNIP水平、细胞凋亡情况;TXNIP过表达慢病毒后,观察E2处理对AD细胞ROS水平和凋亡的影 响。在AD大鼠模型中,观察E2处理后大鼠学习记忆能力和TXNIP的表达变化;过表达TXNIP后,观察E2处理对AD 大鼠模型学习记忆能力的影响。结果：AD细胞中ROS,TXNIP及细胞凋亡水平升高,而E2处理可降低AD细胞ROS, TXNIP及细胞凋亡水平;增强TXNIP表达后,E2处理可降低AD细胞ROS和凋亡水平。与细胞实验类似,E2处理可增 强AD大鼠的学习记忆能力,抑制脑内TXNIP表达;而TXNIP过表达可削弱E2对AD大鼠学习记忆能力的增强效果。 结论：雌激素可通过抑制神经组织中TXNIP的表达,降低神经损伤程度,延缓AD的发生发展。     

纳米医学结合靶向基因治疗阿尔茨海默病治疗中的现状、挑战与未来

阿尔茨海默病（AD）是一种神经退行性疾病,以认知、情感、语言和记忆的进行性损害为主要特征。现有的AD治疗手段主要是药物治疗,但药物治疗仅能改善患者的临床症状,并不能有效延缓病情进展。因此发现并找到有效治疗AD的手段是急需解决的问题。研究已证实基因突变和家族遗传与AD的发生、发展密切相关,且基因治疗在AD动物模型中已有一些进展。同时普通药物与一些常见小分子药物仍面临着无法通过血脑屏障进入脑内发挥作用,而相关通过如免疫逃逸等方法发挥作用的纳米载体则可以很好的解决无法透过血脑屏障的问题。本文综述与AD相关的基因治疗策略,总结现有的基因疗法与纳米医学相结合的 AD治疗理论,并为AD的临床治疗提供新的思路。     

痴呆与脑脊液Tau蛋白含量的关系

目的:探讨痴呆与脑脊液(Cerebrospinal fluid, CSF)Tau蛋白(神经元微管相关蛋白)含量之间的关系,为阿尔茨海默病(Alzheimer′s disease, AD)临床诊断提供生化依据.方法:采用双抗体夹心式ELISA技术,对AD组15例、血管性痴呆(Vascular dementia, VD)组15例、神经系统疾病(Neurologic disease, ND)组20例及正常对照(Normal control, NC)组20例CSF-Tau蛋白含量进行检测,并作比较分析.结果:AD组CSF-Tau蛋白含量明显高于其它各组,差异有高度显著性(P<0.01);AD三个不同临床阶段间及CSF蛋白总量正常组与升高组间比较,差异均无显著性(P>0.05);以CSF蛋白总量为因素作直线相关性分析,ND组r=0.16(P>0.05),无相关性;以年龄因素作直线相关性分析,NC组r=0.53(P<0.05),具有正相关性.结论:CSF-Tau蛋白含量检测对AD的临床诊断具有一定的参考价值.     

水通道蛋白4在阿尔兹海默病脑组织间液引流改变中的作用

目的：通过磁共振成像（magnetic resonance imaging, MRI）示踪剂钆喷酸葡胺（gadolinium-diethylene triamine pentacetic acid, Gd-DTPA）在脑组织间隙（extracellular space,ECS）内扩散的特征,反映大鼠阿尔兹海默病（Alzheimer’s disease,AD）脑组织间液（interstitial fluid,ISF）引流的改变及水通道蛋白4（aquaporin-4,Aqp4）在AD中发挥的作用。方法：将野生型SD大鼠（300～350 g）和Aqp4基因敲除（Aqp4-/-）SD大鼠(300～350 g)分别分为Sham组（10只）、AD组（10只）、Aqp4-/--Sham组（10只）、Aqp4-/--AD组（10只）。Sham组和Aqp4-/- Sham组连续6周每天腹腔注射生理盐水,AD组和Aqp4-/- AD组连续6周每天腹腔注射D-半乳糖。将示踪剂Gd DTPA（10 mmol/L,2 μL）注射到大鼠海马区,分别于0.5 h、1 h、1.5 h、2 h、3 h 进行MRI扫描,观察示踪剂在海马区的动态分布,并测量示踪剂的扩散速率D*值、清除速率k′ 值和半衰期t1/2值。结果：Sham组示踪剂在ECS 内的扩散率D*值为（2.66±0.36）×10-6 mm2/s,AD组D*值（2.72±0.62）×10-6 mm2/s ,Aqp4-/--Sham组D*值（2.75±0.47）×10-6 mm2/s,Aqp4-/--AD组D*值（2.802±0.55）×10-6 mm2/s,4组之间差异无统计学意义（One-Way ANOVA,P>0.05）。Sham组海马区的示踪剂清除速率k′ 为（4.57±0.14）×10-4/s,AD组k′ 为（3.68±0.22）×10-4/s,Aqp4-/- Sham组k′ 为（3.17±0.16）×10-4/s,Aqp4-/--AD组k′ 为（2.59±0.19）×10-4/s,4组之间两两比较差异均具有统计学意义（one-way ANOVA,P<0.05）,4组之间的示踪剂清除半衰期t1/2值依次延长,Sham组海马区的t1/2为（0.67±0.12） h,AD组t1/2为(0.88±0.08) h,Aqp4-/- Sham组t1/2 为（1.12±0.15） h,Aqp4-/- AD组t1/2 为（1.58±0.11） h,两两比较差异均具有统计学意义（One-Way ANOVA,P<0.05）。结论：AD的退行性病变使脑内ISF引流减慢,Aqp4的缺失使AD大鼠脑内ISF引流明显减慢,Aqp4对清除脑组织间隙的代谢废物具有重要作用。