血管性痴呆患者血清维生素B12变化

该研究应用放射免疫分析法检测34例卒中后血管性痴呆(VD)患者及30例卒中后非痴呆患者血清中维生素B12的水平，以探讨维生素B12与VD的关系。     

血管性痴呆与脑白质疏松的相关研究

目的探讨血管性痴呆(VaD)与脑白质疏松症(LA)的相关性.方法对104例LA患者应用分级法将LA分为4级LA1-LA4;应用MMSE和Hachinski量表诊断VaD.结果与LA1组比较,LA3LA4组VaD发生率有明显上升(P＜0.01),MMSE评分有明显下降(P＜0.01).结论LA的损伤程度与VaD发生率呈正相关,LA分级愈高,痴呆的程度愈重.     

血管性痴呆患者血清叶酸、维生素B12水平的改变

研究[1.2]发现缺乏叶酸、维生素B12与脑功能障碍尤其与老年人认知功能障碍有关.本研究观察血管性痴呆(VD)患者的血清叶酸、维生素B12水平改变.现报告如下.     

老年性血管性痴呆与脑白质疏松的相关研究

目的　探讨老年性血管性痴呆 (VD)与脑白质疏松症 (LA)的相关性。方法　对 5 4例 6 0岁以上LA患者的临床及CT和 /或MRI进行 3年跟踪观察 ,应用分级法观察LA的损伤程度 ;应用MMSE和Hachinski量表诊断VD。结果　 5 4例LA患者损伤程度Ⅰ～Ⅲ级变化分别为第 1年 34、14、6例 ,第 2年 17、19、18例 ,第 3年 8、17、2 9例。患老年性VD者第 1年 6例 ,第 2年 13例 ,第 3年 33例 ,平均年增长率为 32 %。结论　LA是老年性VD发生的早期危险信号 ,LA的损伤程度与老年性VD的发生呈正相关 (r=0 .82 ,P <0 .0 5 ) ,应当积极预防和治疗。     

甲基维生素B12对多发性硬化模型大鼠的作用

研究甲基维生素Bi2对脱髓鞘的修复作用.以实验性自身免疫性脑脊髓炎作为多发性硬化的动物模型.用豚鼠脊髓匀浆和完全弗氏佐剂诱导Lewis大鼠发生实验性自身免疫性脑脊髓炎(experimental auto-immuneencephalomyelitis,EAE),给予不同剂量的甲基维生素B12,观察体重变化、神经系统评分和组织学检查.注射甲基维生素B12(266 μg/kg,532μg/kg)增加大鼠的缓解比例,由35.7%增至60%.降低死亡率,由52.3%降为16.70%,减少体重(g)下降量,由18.9±15.6降到4.8±9.5.组织学检查证实甲基维生素B12有促进髓鞘修复的作用.提示,较大剂量甲基维生素B12对多发性硬化模型大鼠有确切良好作用.     

甲基维生素B12对多发性硬化模型大鼠的作用

研究甲基维生素B12 对脱髓鞘的修复作用。以实验性自身免疫性脑脊髓炎作为多发性硬化的动物模型。用豚鼠脊髓匀浆和完全弗氏佐剂诱导Lewis大鼠发生实验性自身免疫性脑脊髓炎 (experimentalauto immuneen cephalomyelitis,EAE) ,给予不同剂量的甲基维生素B12 ,观察体重变化、神经系统评分和组织学检查。注射甲基维生素B12 (2 6 6 μg/kg ,5 32 μg/kg)增加大鼠的缓解比例 ,由 35 .7%增至 6 0 %。降低死亡率 ,由 5 2 .3%降为 16 .70 % ,减少体重 (g)下降量 ,由 18.9± 15 .6降到 4 .8± 9.5。组织学检查证实甲基维生素B12 有促进髓鞘修复的作用。提示 ,较大剂量甲基维生素B12 对多发性硬化模型大鼠有确切良好作用。     

血管性痴呆与偶然发现的白质损害

血管性痴呆与偶然发现的白质损害周国庆，金永清，孙中玉老年人脑白质常在ＭＲＩＴ２加权像出现高密度信号。这些改变多与以前的临床症状无联系。有研究认为，这种皮质下偶然发现的损害（１Ｌｓ）与痴呆有关。本文对血管性痴呆的１Ｌｓ进行探讨。对象与方法一、对象：研究...     

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。     

血管性痴呆大鼠N-甲基-D-天冬氨酸-2B受体变化机制的研究

目的 研究血管性痴呆（VD）大鼠形成过程中N-甲基D-天冬氨酸-2B受体（NR2B）的变化规律及作用机制.方法 永久性结扎双侧颈总动脉制备VD大鼠模型,用Morris水迷宫衡量大鼠的学习记忆水平,用免疫组化法检测大鼠海马NR2B的表达.结果 随缺血时间延长,VD大鼠的学习记忆能力下降,缺血4周后与对照有显著差异（P＜0.01）;NR2B的表达随缺血时间变化,呈先升后降改变,缺血2周时表达最多,与对照有显著差异（P＜0.01）,此后逐渐减少,并明显低于对照组（P＜0.01）,缺血16周时表达最少.结论 VD大鼠学习记忆的改变与海马NR2B的变化相关,缺血早期NR2B过表达产生神经毒引起该能力下降;而在慢性缺血期,这种损害则是因NR2B含量不足难以完成生理功能所致.     

叶酸、Vitamin B12与血管性痴呆

自从十九世纪五十年代Addison(英国)第一次描述恶性贫血伴有的神经精神症状,经用Vit B12、叶酸(folicacid)可逆转之后人们逐渐认识到叶酸、Vit B12缺乏可造成神经系统的损伤.近年来的研究发现叶酸、Vit B12与脑功能障碍尤其与老年人认知障碍有关.从近十几年发表的有关血管性痴呆(Vascular dementia,VD)文献来看,叶酸、Vit B12水平下降或缺乏与VD及认知障碍有关,并研究探讨了其作用机制和叶酸、Vit B12对VD及认知功能的改善效果.     

慢性前脑缺血致痴呆大鼠皮质及皮质下白质区病理学变化的对比研究

目的对比研究慢性前脑缺血致血管性痴呆(VD)大鼠额叶、颞叶皮质、海马及皮质下白质区的病理学变化，探讨血管性痴呆发病的病理基础。方法采用双侧颈总动脉永久结扎方法制备慢性前脑缺血致VD大鼠动物模型；通过常规HE及LFB染色，对比观察缺血后不同时间点大鼠额、颞叶皮质、海马区及皮质下白质的形态学改变；应用HPIAS-1000高清晰彩色病理图文分析系统进行图像分析．检测皮质下白质神经纤维脱失情况。结果HE染色结果显示：缺血1个月时额、颞叶皮质及海马区以锥体细胞缺血的改变为主，逐渐转变为锥体细胞凝固性坏死、变性、脱失及星形胶质细胞增生，少数大鼠额叶出现梗死灶；缺血1个月起实验组大鼠皮质下白质神经纤维疏松、断裂、脱失，且有随缺血时间延长而逐渐加重的倾向；图像分析显示缺血1个月实验组大鼠脑白质神经纤维脱失，出现囊泡样改变并逐渐增重。结论进行性的额、颞叶皮质、海马神经元退变以及皮质下白质损害是VD的病理基础，且白质区的损害要早于皮质。     

Depressive symptoms and white matter changes in patients with dementia

OBJECTIVE: The aim of the present study was to investigate if depressive symptoms in demented patients are associated with white matter changes (WMCs) in the brain. BACKGROUND: WMCs are frequently found in patients with dementia, as well as among elderly nondemented patients with depressive symptoms. However, it is less established whether or not WMCs are related to depressive symptoms in demented patients. METHODS: 67 (26 men, 41 women) patients with primary degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The patients were young-old (mean 68.1, SD 7.3). All patients underwent a standardized examination procedure and MRI of the brain. The degree of WMCs was visually rated, blindly. Depressive symptoms were rated according to the Gottfries-Br?ne-Steen scale (anxiety, fear-panic, depressed mood). RESULTS: No significant relationship was found between WMCs and depressive symptoms in the demented patients. CONCLUSION: The possible involvement of WMCs in the pathogenesis of depressive symptoms in dementia is unclear. A link between disruptions of frontal-subcortical pathways, due to WMCs, and depressive symptomatology in dementia has been hypothesised from earlier findings, which would imply common elements of pathogenesis for depressive symptomatology and cognitive impairment in dementia. However, the results of the present study do not add further support to this hypothesis.     

Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions

Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 ± 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 ± 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.     

慢性间断缺氧对老年期大鼠脑白质的影响

目的研究慢性间断缺氧对老年期大鼠脑白质的影响。方法建立老年期SD大鼠慢性间断缺氧模型,免疫组化检测大鼠脑室旁白质髓鞘碱性蛋白（myelin basic protein,MBP）、神经微丝H＋L（neutofilament—H＋L,NF-H＋L）、胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）表达并行图像分析;电镜下观察大鼠脑内髓鞘、轴突的超微结构。结果慢性间断缺氧可使老年期大鼠脑白质MBP、NF-H＋L表达减少及GFAP表达增加（P均〈0．05）,MBP与NF-H＋L呈高度正相关（R^2=0．908,P〈0．01）。电镜观察与空白对照组比较,缺氧组大鼠脑内可见较多的髓鞘脱失、轴突受损。结论慢性间断缺氧可对老年期大鼠脑白质产生不良影响,表现为髓鞘脱失、轴突变性以及神经胶质增生。     

Longitudinal white matter changes in frontotemporal dementia subtypes

Frontotemporal dementia is a degenerative brain condition characterized by focal atrophy affecting the frontal and temporal lobes predominantly. Changes in white matter with disease progression and their relationship to grey matter atrophy remain unknown in FTD. This study aimed to establish longitudinal white matter changes and compare these changes to regional grey matter atrophy in the main FTD subtypes. Diffusion and T₁‐weighted images were collected from behavioral‐variant FTD (bvFTD: 12), progressive non‐fluent aphasia (PNFA: 10), semantic dementia (SD: 11), and 15 controls at baseline and 12 months apart. Changes in white matter integrity were established by fractional anisotropy, mean, axial and radial diffusivity measurements using tract‐based spatial statistics. Patterns of cortical grey matter atrophy were measured using voxel‐based morphometry. At baseline, bvFTD showed severe cross‐sectional changes in orbitofrontal and anterior temporal tracts, which progressed to involve posterior temporal and occipital white matter over the 12‐month. In PNFA, cross‐sectional changes occurred bilaterally in frontotemporal white matter (left > right), with longitudinal changes more prominent on the right. Initial white matter changes in SD were circumscribed to the left temporal lobe, with longitudinal changes extending to bilateral frontotemporal tracts. In contrast, progression of grey matter change over time was less pronounced in all FTD subtypes. Mean diffusivity was most sensitive in detecting baseline changes while fractional anisotropy and radial diffusivity revealed greatest changes over time, possibly reflecting different underlying pathological processes with disease progression. Our results indicate that investigations of white matter changes reveal important differences across FTD syndromes with disease progression. Hum Brain Mapp 35:3547–3557, 2014. © 2013 Wiley Periodicals, Inc .     

血管性痴呆患者与认知正常老年人颅脑CT表现的对照研究

目的探讨血管性痴呆(vascu lar dem en tia,VD)与颅脑CT所发现的脑白质病变(W h ite m atter le-s ions,WM L)和脑萎缩的可能关系。方法病例对照研究,VD 60例,年龄和性别相匹配的认知正常老年人(cogn i-tive norm a l con tro ls,NC)84例。结果单因素分析显示WM L总分、双侧额区以及双侧顶枕区WM L评分;钩间距、左、右外侧裂宽度、三脑室宽度、哈氏值、脑室指数和侧脑室体部指数在VD与NC之间均有显著差异(P<0.05)。多因素分析结果说明,WM L总分、左额区WM L、三脑室宽度和左侧裂宽度与VD显著相关,其OR值(95%可信区间)分别为1.53(1.26~1.86),4.13(2.19~7.79),2.64(1.74~4.00),1.37(1.06~1.76)。结论尽管脑血管病变是导致VD发生的直接原因,但脑白质病变、脑萎缩以及三脑室扩大所反映的丘脑受累均与VD密切相关,提示VD的发病可能涉及多种因素的复杂作用。     

Profiles of white matter tract pathology in frontotemporal dementia

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template‐based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co‐localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. Hum Brain Mapp 35:4163–4179, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Perivascular deposits of serum proteins in cerebral cortex in vascular dementia

Summary Immunocytochemical techniques were used to study the histopathologic changes in vascular dementia, i. e., both multi-infarct dementia (MID) and MID combined with Alzheimer changes (MID/SDAT). In eight of 13 of the dementia cases strongly immunostained deposits of plasma proteins were observed around numerous capillaries of layers I–IV of frontal grey matter. Each of these deposits contained albumin, prealbumin, IgG, C1q, C3c, and fibrinogen. No such deposits were found in any of the seven nondemented aged controls. In contrast, in white matter in both demented and normal aged control cases only weak immunostaining of serum proteins was observed which gradually decreased with the distance from the vessels. The presence of heavy deposits of serum proteins exclusively around the capillaries of the gray matter in cases with vascular dementia may indicate a defect of the cortical capillary system which might play a role in the clinical symptoms seen in vascular dementia. The enrichment of C1q within the deposits is intriguing as this might occur because of the binding of C1 through its subunit C1q to the antibody-antigen complex and thereby support a possible immunologic involvement in the formation of these deposits.Supported by grants from the Swedish Medical Research Council, King Gustaf Vth and Queen Victoria's foundation, Osterman's, Pfannenstill's, Mångberg's, and Thuring's foundations