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。     

同型半胱氨酸与阿尔茨海默病及血管性痴呆

目的研究同型半胱氨酸(Homocysteine,Hcy)及叶酸、维生素B_(12)与阿尔茨海默病(Alzheimer Dis- ease,AD)和血管性痴呆(Vascular dementia,VaD)的关系,并通过Hcy揭示AD发病的血管危险因素。方法用美国国立神经病学、语言障碍和卒中-阿尔茨海默病和相关疾病学会(NINCDS-ADRDA)标准的可能标准严格筛选AD患者35例,用ADDTC诊断标准筛选VaD患者30例,并同期选择31例无临床脑血管病史、无认知功能障碍的健康查体中心志愿者为对照组。取肝素抗凝的血浆用循环酶法进行Hcy的测定。取血清由全自动化学发光免疫检测仪进行叶酸和维生素B_(12)的测定。结果AD组和VaD组血浆Hcy水平显著高于对照组,血清叶酸和VitB_(12)水平显著低于对照组。VaD组存在痴呆程度越高血浆Hcy水平越高这一显著正相关关系,而AD组这一正相关关系无统计学意义;且发现VaD组患者MMSE评分越低其血浆Hcy水平越高这一显著负相关关系,而AD组这一关系仍无统计学意义。在所有研究对象中存在血浆Hcy水平与血清叶酸及VitB_(12)水平的显著负相关关系。结论提示高Hcy血症可能是引起AD和VaD的一个重要危险因素,Hcy作为一个新的血管因素加强了AD与血管危险因素之间的联系,并且提示积极治疗高Hcy血症在预防AD和VaD方面可能有积极意义。     

Lack of association between interleukin-1alpha polymorphism and Alzheimer disease or vascular dementia

Recently, a C/T polymorphism in the promoter region of the interleukin 1-alpha (IL-1alpha) gene (position -889) was reported to be associated with Alzheimer disease. In this study, the polymorphism of IL-1alpha was examined in patients with Alzheimer disease, vascular dementia, and nondemented controls in a Chinese population in Taiwan. No difference was found in the IL-1alpha T allele frequency among the three groups. The predominant polymorphic allele ( approximately 90%) of IL-1alpha was the C allele. The APOE4 allele was overrepresented in the AD cohort. The presence of the APOE4 allele did not influence the IL-1alpha genotype or allele distribution. The prevalence of the IL-1alpha T allele, in particular the homozygous form, was lower than in whites and may account for the lack of association between IL-1alpha C/T polymorphism and Alzheimer disease among Chinese in Taiwan. The presence of the heterozygous IL-1alpha T allele cannot be used for distinguishing Alzheimer disease or vascular dementia from controls.     

Relation of plasma lipids to Alzheimer disease and vascular dementia

BACKGROUND: The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear. OBJECTIVE: To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship. DESIGN AND SETTING: Cross-sectional and prospective community-based cohort studies. PARTICIPANTS: Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY. MAIN OUTCOME MEASURES: Vascular dementia and AD according to standard criteria. RESULTS: Elevated levels of non-high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. CONCLUSIONS: We found a weak relation between non-HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD.     

Activation-flow coupling differentiates between vascular and Alzheimer type of dementia

The activation-flow coupling describes a mechanism, which adapts local cerebral blood flow in accordance with the underlying neuronal activity. It was suggested that the mechanism helps in differentiation between Alzheimer and vascular type of dementia. We combined EEG and Doppler techniques and assessed integrity of the activation-flow coupling in the occipital cortex utilizing a visual stimulation task. Alzheimer patients (MMSE: 18+/-8 points, DemTect 5+/-4 points) without signs of vascular lesions on a MRI scan and vascular demented patients (MMSE: 20+/-6 points, DemTect 6+/-3 points; MRI Fazekas score 7+/-3 points) were compared with data from an age-matched control group. Evoked flow velocity responses in the posterior cerebral artery were analysed according to a control system model specifying the parameters gain, attenuation, natural frequency and rate time. Evoked potentials were analysed for the N(75)-P(100) amplitude difference. Vascular demented patients exhibited a significant decreased gain parameter and increased attenuation parameter indicating severe cerebrovascular dysfunction. Also, the potential amplitudes were significantly decreased indicating neuronal damage due to the vascular disease process. Alzheimer patients did not differ in parameters as compared to the control group supporting other reports of intact occipital function at this stage of disease. Simultaneous assessment of electrical as well as vascular integrity might help in differentiating the most frequent forms of dementia.     

脑脊液生物学标志物诊断阿尔茨海默病与血管性痴呆

目的探讨脑脊液β-淀粉样蛋白（Aβ1～42）、tau蛋白和磷酸化tau蛋白诊断阿尔茨海默病与血管性痴呆的敏感性和特异性。方法采用酶联免疫吸附法检测阿尔茨海默病与血管性痴呆患者脑脊液中Aβ1～42、tau蛋白和磷酸化tau蛋白浓度的变化,根据受试者工作特征曲线观察脑脊液中这3种生物学标志物用于诊断阿尔茨海默病与血管性痴呆的敏感性和特异性;采用单因素方差分析以及受试者工作特征曲线对所获结果进行统计学分析。结果阿尔茨海默病组患者脑脊液Aβ1～42浓度低于对照组（P=0.010）,tau蛋白浓度高于对照组（P=0.001）和血管性痴呆组（P=0.030）,磷酸化tau蛋白浓度高于对照组（P=0.004）。脑脊液Aβ1～42、tau蛋白和磷酸化tau蛋白用于诊断阿尔茨海默病的敏感度为60.00%～96.70%,特异度可达70.00%～90.00%。Aβ1～42、tau蛋白和磷酸化tau蛋白联合检测可提高阿尔茨海默病与血管性痴呆鉴别诊断的敏感性和特异性,敏感度可达86.57%,特异度为90.00%。结论脑脊液Aβ1～42、tau蛋白和磷酸化tau蛋白浓度的变化,不仅对诊断阿尔茨海默病具有较高的敏感性和特异性,而且亦可作为阿尔茨海默病与血管性痴呆鉴别诊断的生物学指标。     

Lysosomes,autophagosomes and Alzheimer pathology in dementia with Lewy body disease

A failure of protein degradation may underpin Lewy body disease (LBD) where α‐synuclein is assimilated into the pathognomic Lewy bodies and Lewy neurites. We investigated histological alterations in lysosomes and autophagosomes in the substantia nigra (SN) and cingulate gyrus (CG) in 34 patients with LBD employing antibodies against phosphorylated α‐synuclein and lysosomal (lysosomal associated membrane proteins 1 and 2 (LAMP‐1 and LAMP‐2), cathepsin D (CTSD)) and autophagosomal (microtubule‐associated protein light chain 3α (LC3A)) proteins. Immunostained sections were qualitatively and semi‐quantitatively assessed for the appearance, distribution and intensity of staining. Four LBD patients had mutations in GBA1. There was significantly less LAMP‐1, LAMP‐2 and CTSD immunostaining in neurons of the SN in LBD cases compared to control cases and marginally less LAMP‐1 in patients with GBA1 mutations compared to those without. Loss of LAMP‐1 and CTSD immunoreactivity correlated with cell loss from the SN. There were no changes in LC3A immunoreactivity in the SN, nor any major changes in the CG, or glial cell activity in the SN and CG, for any of the markers. A proportion of amyloid plaques in both the LBD and control cases was immunoreactive for LAMP‐1 and LAMP‐2, but not CTSD or LC3A proteins. These immunohisochemical features were seen in glial cells, which were negative for amyloid‐β. Alterations in lysosomal structure or function, but not macroautophagy, may underpin the pathogenesis of LBD.     

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.     

Treatment effect size of memantine therapy in Alzheimer disease and vascular dementia

The purpose of this paper is to assess the clinical relevance of the significant results reported in clinical trials of memantine therapy for Alzheimer disease (AD) and vascular dementia. We sought to understand what clinically detectable changes would be evident to the patient with dementia, their caregivers, and the treating physician during a trial of memantine therapy. A literature search was performed on MedLine, PsycInfo, and the Cochrane database. The statistically significant findings from the memantine literature were reviewed using treatment effect size as a measure of clinical meaningfulness. There have been 3 phase 2 studies of memantine in dementia, and 6 phase 3 studies published as of August 1, 2005. Of the 6 published phase 3 trials of memantine in dementia; 2 were in mild-moderate vascular dementia, 1 in mild-moderate AD, 2 in moderate-severe AD, and 1 in severe dementia (both AD and vascular dementia). The most convincing evidence of a clinically meaningful treatment effect of memantine therapy is in the moderate-severe AD patient population. Cognition, as measured by the Severe Impairment Battery, had an effect size of 0.32 and 0.49 in the 2 published trials, indicating a small-to-medium effect of the medication. Global, functional, and behavioral scales also showed a small-to-medium response to memantine.     

阿尔茨海默病、血管性痴呆血脂浓度分析

目的：研究阿尔茨海默病（AD）、血管性痴呆（VD）及轻微认知功能损害（MCI）患者血脂水平的特点。方法：所有研究对象均来自广州市城乡社区及养老院。痴呆诊断采用美国精神障碍诊断与统计手册第4版的标准,MCI诊断参照Petersen的标准。采用酶法进行血脂测定。结果：AD、VD、MCI及正常老人血浆总胆固醇（TC）、三酰甘油（TG）浓度差异无显著性（P〉0．05）。按痴呆程度分组,中度、重度AD患者血浆TG浓度、重度AD患者血浆TC浓度均显著低于正常老人及轻度AD患者（P〈0．05）;轻度AD患者与正常老人血浆TC、TG浓度的差异无显著性（P〉0．05）。不同程度VD患者及正常老人血浆TC和TG浓度的差异无显著性（P均〉0．05）。结论：VD、MCI及轻度AD患者的血浆TC、TG浓度与正常老人相似。AD患者痴呆程度越重,血浆TC、TG浓度越低。