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。     

Overlap between pathology of Alzheimer disease and vascular dementia

There is overwhelming evidence to suggest that the neuropathology of Alzheimer disease (AD) extends beyond amyloid plaques and neurofibrillary tangles. Review of various consortium data shows that more than 30% of AD cases exhibit cerebrovascular pathology. However, certain vascular lesions such as cerebral amyloid angiopathy, microvascular degeneration, and periventricular white matter lesions are evident in almost all cases of AD. Whether these vascular lesions are coincidental or causal in the pathogenetic processes of AD remains to be defined. Although systemic vascular influences such as hypertension, coronary artery disease, and other cardiovascular disturbances may be responsible for such pathology in AD, it is equally intriguing that about one third of patients diagnosed with vascular dementia (VaD) will have AD-type pathology at autopsy. Moreover, previous studies have revealed that deficits in cholinergic indices related to the basal forebrain neurones are apparent in multi-infarct dementia. In this short review, we evaluate cerebrovascular pathology of AD in light of peripheral vascular pathophysiology implicated in the etiopathogenesis of the dementia. We also consider pathological findings in relation to genetic influences such as apolipoprotein E that may shed light on the link between AD and VaD. In view of these commonalties, it is reasonable to consider the same treatment strategies for both AD and VaD.     

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。     

Decreased myelin lipids in Alzheimer''s disease and vascular dementia

The lipid composition of white matter and myelin from the semioval centre was studied in autopsy material from cases with Alzheimer's disease (AD) (n = 11), vascular dementia (VD) (n = 7), and age-matched controls (n = 11). In AD and VD the white matter content of phospholipids and cholesterol was reduced to 72-76% of the control values (P less than 0.01), the diminution of cerebrosides and sulphatides was more pronounced (55-69%) (P less than 0.001) while the concentration of gangliosides did not change significantly (87-90%). The myelin composition was the same in the 3 groups, suggesting that the white matter involvement is not caused by alteration of the myelin structure. The altered lipid composition in white matter in AD and VD suggests that the myelin sheath is the primary lesion site.     

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。     

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。     

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.     

Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia

Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.     

Body mass index in midlife and risk of Alzheimer disease and vascular dementia

Prior work has suggested that obesity and overweight as measured by body mass index (BMI) increases risk of dementia. It is unknown if there is a difference in the risk of developing Alzheimer disease (AD) versus vascular dementia (VaD) associated with high body weight. The goal of this study was to examine the association between midlife BMI and risk of both AD and VaD an average of 36 years later in a large (N= 10,136) and diverse cohort of members of a health care delivery system. Participants aged 40-45 participated in health exams between 1964 and 1968. AD and VaD diagnoses were obtained from Neurology visits between January 1, 1994 and June 15, 2006. Those with diagnoses of general dementia from primary care providers were excluded from the study. BMI was analyzed in WHO categories of underweight, overweight and obese, as well as in subdivisions of WHO categories. All models were fully adjusted for age, education, race, sex, marital status, smoking, hyperlipidemia, hypertension, diabetes, ischemic heart disease and stroke. Cox proportional hazard models showed that compared to those with a normal BMI (18.5-24.9), those obese (BMI > or = 30) at midlife had a 3.10 fold increase in risk of AD (fully adjusted model, Hazard Ratio=3.10, 95% CI 2.19-4.38), and a five fold increase in risk of VaD (fully adjusted model, HR=5.01, 95% CI 2.98-8.43) while those overweight ( BMI > or = 25 and <30) had a two fold increase in risk of AD and VaD (fully adjusted model, HR=2.09, 95% CI 1.69-2.60 for AD and HR=1.95, 95% CI 1.29-2.96 for VaD). These data suggest that midlife BMI is strongly predictive of both AD and VaD, independent of stroke, cardiovascular and diabetes co morbidities. Future studies need to unveil the mechanisms between adiposity and excess risk of AD and VaD.     

脑血管病性痴呆与Alzheimer病患者脑局部区域的血流量

目的 测定多灶脑梗塞痴呆及Ａｌｚｈｅｉｍｉｅｒ病患者的脑局部区域的血流量（ｒＣＢＦ）,方法 用＾１３３氙（＾１３３Ｘｅ）吸入法测定１０例多灶脑梗塞痴呆患者。１０例Ａｌｚｈｅｉｍｅｒ病及２０名正常人的ｒＣＢＦ。结果 两个病例组双半球,脑干－小脑ｒＣＢＦ均明显低于正常健康组,脑梗塞痴呆组多数病例双侧半球灰质ｒＣＢＦ降低呈斑块状,Ａｌｚｈｅｉｍｅｒ病例组均为双侧大脑半球弥散性对称性的ｒＣＢＦ降低,前乾脑     

Alzheimer disease and vascular dementia: relationships with fasting glucose and insulin levels

Cerebrovascular disease and Alzheimer disease are the leading causes of dementia in elderly subjects. In spite of it, relatively little is known about the pathogenesis and risk factors for dementia. We evaluated fasting plasma glucose and insulin, albumin, lipids, Lp(a) and uric acid levels in nondiabetic patients of both sexes affected by vascular dementia (VD) and senile dementia of the Alzheimer type (SDAT) as well as in a control group of age-matched nondemented subjects. Following a covariance analysis by gender, body mass index, albumin levels and prevalence of arterial hypertension, total and LDL cholesterol as well as HDL cholesterol levels were not significantly different among the three groups. Fasting glucose (p < 0.001 and p < 0.005, respectively) and insulin levels (p < 0.05 for both differences) were higher in patients with VD and SDAT than in control subjects. Our data show that nondiabetic patients with VD or SDAT have higher fasting glucose and insulin levels than healthy control subjects. These metabolic characteristics were not influenced by differences in gender, adiposity, nutritional status, lipids or presence of arterial hypertension.     

Acetylcholinesterase activity in CSF in senile dementia of Alzheimer type, vascular dementia, and Parkinson's disease

Acetylcholinesterase (AChE) activity was measured in cerebrospinal fluid (CSF) from 25 patients with senile dementia of Alzheimer type (SDAT), 11 patients with vascular dementia (VD), 26 patients with Parkinson's disease (PD), and 30 normal controls. AChE activity also was measured in 46 normal subjects whose ages ranged from 15 to 85 to evaluate the effect of age on AChE activity. CSF AChE activity for the SDAT, VD and PD groups showed no significant difference compared with the value for the control group. However, there were significant decreases in CSF AChE activity in the VD and PD groups with the development of ventricular enlargement. There was no significant correlation between CSF AChE activity decrease and ventricular enlargement in the SDAT group. AChE activity increased significantly over the age range of 15 to 85. These results suggest that, although CSF AChE activity is not a useful parameter in the diagnosis of dementia, it may be a marker indicating abnormalities of the intracerebral cholinergic system during the process of cerebral atrophy.