血管性痴呆患者SPECT脑血流灌注显像特点

目的　探讨血管性痴呆 (VD)患者 SPECT局部脑血流灌注显像特点 ,为 VD的早期诊断和痴呆严重程度的评估寻找客观的生物学指标。方法　分别对 45例 VD、3 0例卒中无痴呆 (SWD)和 3 0例正常对照者 (NC)3组进行 SPECT局部脑血流灌注显像 ,半定量分析各脑区血流灌注情况。结果　 VD组额叶、顶叶、颞叶和基底节局部脑血流灌注比 SWD组减少 (P<0 .0 5 ) ;并以额叶、颞叶血流灌注的减少最为显著 (P<0 .0 1)。与 NC组相比 ,SWD组额叶、顶叶、颞叶和基底节局部脑血流灌注均减低 (P<0 .0 5 )。额叶、颞叶血流灌注减低与 MMSE评分间存在正相关关系 (r=0 .75 5 ,P<0 .0 1)。结论　 VD患者存在明显的脑血流灌注减低 ,以额叶、颞叶最为显著 ,且与MMSE评分间存在正相关 ,SPECT脑血流灌注显像有助于 VD的诊断和病情评估     

Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia

Summary The acetylcholine (ACh) and choline (Ch) concentrations in the cerebrospinal fluid were investigated in patients with vascular dementia of the Binswanger type (VDBT) or multiple small infarct type (MSID) as compared with patients with Alzheimer-type dementia (ATD). The ACh concentration in patients with ATD was found to be significantly lower than in controls (73%, p < 0.0001), and showed a significant positive correlation with dementia scale scores (r_s=0.63, p < 0.03). The Ch concentration in the CSF of ATD patients was approximately the same as in controls. In VDBT/MSID patients, the ACh concentration was significantly lower than in controls (p < 0.001), also showing a significant positive correlation with dementia scale scores (r_s=0.62, p < 0.02), but was significantly higher than in ATD patients (p < 0.001). Moreover, the Ch concentration in VDBT/MSID patients was significantly higher than in controls (p < 0.001) or ATD patients (p < 0.001). These results suggest that simultaneous determination of ACh and Ch concentrations in CSF may be useful for differentiating VDBT/MSID from ATD and that increasing the ACh level using cholinergic agents may be a beneficial therapeutic strategy for the treatment of ATD as well as VDBT/MSIT, and is worthy of further investigation.     

CSF biomarker profile and diagnostic value in vascular dementia

Background and purpose:  The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (τ_T) or hyperphosphorylated at threonin-181(τ_P-181) form and beta amyloid peptide 1–42 (Aβ42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD.
Methods:  The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls.
Results:  Alzheimer's disease and MD showed increased levels of τ_T, τ_P and reduced levels of Aβ42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying ≥85% of patients, either in the form of a discriminant function or in the form of the τ_T × τ_P-181/Aβ42 formula.
Conclusions:  Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.     

Serum and cerebrospinal fluid cystatin C levels in vascular and Alzheimer's dementia

INTRODUCTION: Cystatin C, a cysteine protease inhibitor, has been implicated in the neurodegenerative and repair processes of the nervous system, and the deposition of the same protein together with beta amyloid peptide was found as cerebral amyloid angiopathy (CAA) in different types of dementias. OBJECTIVE AND METHODS: Because of the differential diagnostic importance, serum and cerebrospinal fluid (CSF) cystatin C levels of 24 late onset Alzheimer's demented (AD) and 16 ischemic type of vascular demented (VD) probands were compared with 17 aged control (AC) persons. RESULTS: The serum and CSF cystatin levels were found in the normal range in all groups. The ischemic VD probands had the tendency to have higher cystatin C levels than the AD. No correlation has been found with the severity and duration of dementia and with the other measured parameters. CONCLUSION: These results indicate that lower than normal CSF cystatin C level is not a diagnostic marker in ischemic VD and CAA related to AD.     

高同型半胱氨酸血症与血管性痴呆相关性研究

目的:探讨血浆同型半胱氨酸(Hcy)水平与血管性痴呆(VD)的相关性。方法:应用全自动生化分析仪用循环酶法检测37例VD患者的血浆Hcy浓度,并与39例非痴呆脑梗死患者作为同龄对照组血浆Hcy浓度进行比较,同时测定血浆叶酸及VitB12浓度,根据简易精神状态检查量表(MMSE)评分划分VD患者严重程度,分为轻度(20～24分),中度(10～19分),重度(10分以下)。结果:VD组血浆Hcy水平显著高于非痴呆脑梗死组(P<0.05),VD组血浆叶酸水平显著低于非痴呆脑梗死组(P<0.05),两组间VitB12水平无显著性差异(P>0.05),不同程度VD患者血浆Hcy、叶酸水平有显著性差异(p<0.05),VitB12水平无显著性差异(p>0.05)。结论:高同型半胱氨酸血症可能是VD发病的一个新的危险因素。     

Change in the equilibrium of the levels of free and bound forms of alpha1-microglobulin and ulinastatin in patients with mood disorders

We have previously found that the relationship between the urinary content of alpha1-microglobulin (alpha1M) and ulinastatin (UT) in patients with mood disorders (MD) differs from that in age-matched healthy subjects. Similar results were obtained for the relationship between the content of free forms of alpha1M and UT in serum, and that between the ratio of the content of free form to the total (free + bound forms) content (F/T ratio) of alpha1M and UT in serum. As for the content of alpha1M and UT in serum, statistical differences were not observed between MD patients and healthy subjects with regard to the respective total content of alpha1M and UT nor the F/T ratio of alpha1M, whereas the F/T ratio of UT was significantly (p < 0.05) lower in MD patients than in healthy subjects. Furthermore, the serum cortisol content was higher in MD patients than in healthy subjects, and a positive correlation between cortisol content and F/T ratios of UT was demonstrated in the present investigation. These results suggest that the equilibrium of free and bound forms of UT in serum, but not of alpha1M, tends to decrease the free-form level of UT in MD patients. The efficiency of cortisol, which might increase the free-form level of UT, markedly deteriorated in MD patients.     

Neurosonographic findings in dementia

We performed neurosonographic examinations in 19 patients with vascular dementia (VD) and compared these findings with those in 21 patients with dementia of the Alzheimer type (DAT) and in 20 controls. There were no significant differences in age and sex among these three subject groups. The severity of dementia quantified by the Mini-Mental State Examination and Mattis Dementia Rating Scale did not reveal significant differences between VD and DAT. We found that carotid stenosis > 50% or occlusion was more frequent in VD compared to controls. The mean flow velocities of both the middle cerebral artery (MCA) and the basilar artery (BA) were decreased in VD and DAT compared with controls. This decrease was statistically significant for left MCA, but not for right MCA and BA. However, we did not find any significant differences between VD and DAT for the mean flow velocities of both MCA and BA.     

Olfactory dysfunction in dementia of Alzheimer's type and vascular dementia

Background: Olfactory function in vascular dementia has not been extensively investigated to date. We studied olfactory function in vascular dementia (VD) and dementia of Alzheimer's type (DAT). Methods: We studied olfactory functioning in 12 patients suffering from dementia of Alzheimer's type, 11 patients with vascular dementia and 30 normal subjects. For these subjects we examined a 12‐item version of the Pennsylvania smell identification test and mini‐mental state examinations. These three groups were matched for age, sex and educational level. Results: Although the dementia scores were comparable in the DAT and VD groups, the smell identifications were low in DAT patients compared with VD patients and normal control subjects. Conclusions: These results suggest that the smell identification test may be useful in differential diagnosis between DAT and VD patients     

Non-existence of a positive correlation between urinary levels of α1 -microglobulin and ulinastatin in patients with Parkinson's disease

Urinary levels of a,-microglobulin (αlM) and of ulinastatin (UT) and the αlM/UT ratio did not differ significantly between age-matched controls and patients with Parkinson's disease, and among subdivided groups based on Yahr's stages in Parkinson's disease. Furthermore, these indexes did not correlate with Yahr's stages. Although αlM and UT levels did not correlate in patients with Parkinson's disease, a positive correlation was observed in the control group. The non-existence of a positive correlation between αlM and UT levels distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorder.     

Impairment of the correlation between urinary contents of alpha-1-microglobulin and ulinastatin is induced by intracerebroventricularly administered interleukin-6 in mice.

We have found previously that the correlation between urinary contents of alpha-1-microglobulin (alpha1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1beta and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1beta and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which alpha1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, alpha1M and UT, and alpha1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1beta or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1beta (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of alpha1M and UT. However, a higher dose of IL-6 (20 ng) nullified the positive correlation for 2 days after administration. Recovery to a positive correlation was thereafter displayed. These findings suggest that central IL-6 plays an important role in correlating urinary contents of alpha1M and UT without affecting the renal functions.     

血管性痴呆患者神经肽Y和降钙素基因相关肽的临床意义

目的探讨血管性痴呆(VD)患者血清神经肽Y(NPY)和降钙素基因相关肽(CGRP)含量的变化及其临床意义。方法采用放射免疫分析法(RIA)测定66例VD患者,59例脑梗死非痴呆(CI)患者及40例健康人(NC)血淸NPY和CGRP含量,并探讨两者的关系。结果 VD组和CI组NPY水平显著高于NC组(P0.01);VD组NPY水平高于CI组(P0.05);VD组和CI组CGRP水平显著低于NC组(P0.01),VD组CGRP水平显著高于CI组(P0.01);VD组CGRP和NPY呈负相关(P0.05)。结论 VD体内CGRP降低,NPY升高,且CGRP与NPY呈负相关。脑血管舒缩功能平衡失调既可能是脑缺血缺氧的结果,又可能是导致脑细胞损伤的重要原因。脑的长期慢性缺血缺氧可能是VD发生发展的主要危险因素。     

Cerebrospinal fluid tau levels in Alzheimer's disease are elevated when compared with vascular dementia but do not correlate with measures of cerebral atrophy

Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset.     

β淀粉样蛋白与生长因子变化与老年性痴呆致病因素的研究

目的：检测血清β淀粉样蛋白（β－ＡＰ）和多肽生长因子含量变化,探讨其在Ａｌｚｈｅｉｍｅｒ病（ＡＤ）和血管性痴呆（ＶＤ）发病机制中的可能作用。方法：采用放射免疫分析法（ＲＩＡ）检测临床诊断为ＡＤ患者８例,ＶＤ患者１５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）的水平,同时与健康对照组比较。结果：ＡＤ与ＶＤ患者β－ＡＰ、ＴＧＦ－α和ＩＧＦ－Ⅱ水平明显高于ＩＣＶＤ组和健康对照组,均具有显著性差异。ＩＣＶＤ患者血清β－ＡＰ、ＴＧＦ－α和 ＩＧＦ－Ⅱ水平亦明显高于对照组,其中以脑梗塞后遗症（ＳＣＩ）和椎基底动脉供血不足（ＶＢＩ）组增高十分明显,与对照组比较差异显著（Ｐ＜０．０５）。ＡＤ与 ＶＤ患者 ３项测定指标之间具有明显的正相关。结论：①β－ＡＰ可能是ＡＤ和ＶＤ发病的危险因素。②引起ＡＤ和ＶＤ神经元毒性作用进而导致痴呆．这可能与ＴＧＦ－α和ＩＧＦ－Ⅱ增多有关。③β－ＡＰ与ＴＧＦ－α、ＩＧＦ－Ⅱ密切相关,在老年斑形成过程中可能起重要作用。     

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia

Objectives. Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. Design. Cross-sectional comparative study. Setting. Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. Methods. Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). Results. Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p=0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p=0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p=0.046). There were no significant differences in LP or TAC between the three groups. Conclusions. Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation. Copyright © 1998 John Wiley & Sons, Ltd.     

Presenilin-1 polymorphism in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia in Japanese population

We investigated the genetic association between intronic polymorphism in Presenilin-1 (PS-1) gene and patients with various types of dementia such as Alzheimer's disease (AD), vascular dementia (VD) and alcohol associated dementia (ALD), in Japanese population. Homozygosity for allele 1 of the PS-1 polymorphism was significantly increased in late-onset sporadic AD, but not in early-onset sporadic AD, familial AD, VD and ALD. When late-onset sporadic AD patients were divided on the basis of apolipoprotein E (APOE) genotype, homozygosity for the allele 1 of the PS-1 polymorphism was significantly increased in patients with late-onset sporadic AD without APOE εe 4 allele, but not in those with APOE εe 4 allele. Intronic mutation in PS-1 gene may be specific and one of the genetic risk factor for late-onset sporadic AD.     

Qualitative analyses of clock drawings in Alzheimer's disease and vascular dementia

Although quantitative analyses of clock drawings (CD) have achieved widespread clinical use as a cognitive screening, little is known about the qualitative profiles of CD in Alzheimer's disease (AD) and vascular dementia (VD). To address this issue, the present study examined the significance of qualitative analyses of CD in AD and VD. Sixty-seven AD patients, 44 VD patients and eight controls underwent a clock drawing test and took the Mini-Mental State Examinations (MMSE). In the dementia groups, quantitative scores significantly decreased compared with controls and were significantly correlated with MMSE scores. Qualitative analysis demonstrated that in AD patients qualitative error patterns were stable and independent of severity. In contrast, in VD patients the frequency of graphic difficulties and conceptual deficit increased, while the frequency of spatial and/or planning deficit decreased, as severity worsened. In mild dementia groups the frequency of spatial and/or planning deficit was significantly higher in VD. In moderate dementia groups, the frequency of graphic difficulties was significantly higher in VD and the difference in the frequency of spatial and/or planning deficit seen in mild dementia disappeared. The present study suggests that qualitative analyses of clock drawings could demonstrate the neuropsychological profiles of AD and VD and their differences between these dementias.     

Severity of vascular dementia is related to volume of metabolically impaired tissue.

The relation between dementia severity and regional cerebral metabolic rate of glucose was studied in 28 patients with vascular dementia (VD) in comparison with 20 age-matched patients who were suffering from Alzheimer's disease (AD) and 24 normal subjects by using positron emission tomography with fludeoxyglucose F 18. Similar metabolic impairment was found in the temporoparietal and frontal association cortex in patients with VD and in those with AD. Metabolism of the basal ganglia, thalamus, and cerebellum was reduced significantly in patients with VD only. The total volume of regions with metabolism below the 95% confidence interval of control values was significantly related to the severity of dementia but did not differ between patients with VD and those with AD. A metabolic ratio of regional cerebral glucose metabolism of association areas divided by regional cerebral glucose metabolism of structures that were typically not affected by AD was significantly lower in patients with AD than in those with VD. This ratio was also related to dementia severity in both types of dementia.     

Cytokines in Alzheimer's disease and vascular dementia

The levels of interleukin 1beta, interleukin 6, and interleukin 10 were elevated in the serum of patients with dementia. No statistically significant correlation was recorded in the interleukin levels among patients with Alzheimer's disease and vascular dementia. Also, no significant correlation was observed in the interleukin levels in the serum and the severity of dementia. However, a significant correlation was found between IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels and age. The levels of IL-1beta and IL-6 were positively correlated with hypertension, and IL-2 levels were negatively correlated. No correlation was found between depressive symptoms and levels of cytokines in the serum.     

Serum brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 levels in dementia

The aim of this study is to measure serum levels of neurotropic factor (NF) in patients with dementia. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) were determined in Alzheimer's dementia patients without medication (AD; n: 22), Alzheimer's dementia patients receiving cholinesterase inhibitor (CEI) treatment (AD?+?CEI; n: 32) and vascular dementia patients receiving CEI treatment (VaD?+?CEI; n: 27) and the age-matched control group (n: 20). NGF levels were detected to be significantly higher in the control group than in AD group (P?相似文献   

Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia patients

OBJECTIVES: To investigate a possible implication of inflammatory processes in the development of dementia in cerebrovascular disease. PATIENTS AND METHODS: We examined the levels of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 26), ischemic cerebrovascular disease without dementia (CVD) (n = 11), vascular dementia (VD) (n = 11), and other neurological disorders (n = 21) using sensitive enzyme-linked immunosorbent assay. RESULTS: The CSF concentrations of IL-6 were significantly elevated in patients with VD compared with those of patients with AD or CVD. CONCLUSION: The CSF IL-6 levels are increased in patients with VD, suggesting that inflammatory mechanisms may be involved in the development of cognitive decline in some patients with cerebrovascular disease. CSF IL-6 may be a biological marker for dementia in cerebrovascular disease.