Lp(a) Lipoprotein in Cerebrovascular Disease and Dementia

Abstract: Lp(a) lipoprotein has been considered an independent risk factor in the development of coronary heart disease (CHD). We examined the role of Lp(a) in patients with cerebrovascular disease (CVD) and those with dementia.
The Lp(a) concentration in patients with CHD, those with cerebral infarction due to a large artery occlusion and those with vascular dementia (VD) was significantly higher than that of age-matched control subjects. However, the Lp(a) concentration was not high in cerebral infarction due to a small artery occlusion, intracerebral hemorrhage and dementia of the Alzheimer type (DAT).
The present results suggest that Lp(a) should cause VD as well as CVD, and that Lp(a) should be one of the indicators that distinguish VD from DAT.     

Lipoprotein(a) phenotypes in patients with vascular dementia

We tried to examine if there is a particular distribution pattern of lipoprotein(a) [Lp(a)] phenotypes specific for patients with vascular dementia (VD). Fourteen cases of VD (9 males and 5 females), 18 cases of dementia of the Alzheimer type (DAT)(7 males and 11 females), 29 cases of cerebrovascular disease (CVD) in the chronic phase (18 males and 11 females) and 47 healthy individuals as controls (25 males and 22 females) were examined for serum Lp(a). Serum concentrations and phenotypes of Lp(a) were assessed by ELISA and a test kit for the Lp(a) phenotype, respectively. Serum concentrations of Lp(a) were significantly higher in patients with VD (p < 0.05) as well as patients with CVD (p < 0.01) compared with those in healthy individuals. Serum concentrations of Lp(a) did not significantly differ between patients with DAT and healthy individuals. The incidences of Lp(a) phenotypes containing relatively low-molecular-weight apolipoprotein(a) isoforms were significantly higher in patients with CVD in the chronic phase (p < 0.05) or those with VD (p < 0.01) compared with those in healthy individuals. Distribution patterns of Lp(a) phenotypes did not differ between patients with DAT and healthy individuals. Thus, high serum levels of Lp(a) could be considered a clinical hallmark to distinguish VD from DAT. Abnormally high serum levels of Lp(a) in patients with CVD and VD seemed to be due to specific increases in low-molecular-weight apolipoprotein(a) isoforms in Lp(a).     

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.     

Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia

The phenotypes of apolioprotein E (ApoE) in the plasma of patients with dementia of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the control subjects, the frequency of the ApoE ε4 allele was significantly higher in the DAT group as well as the VD group, but was not significantly different in the cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE mRNA level in the DAT group and the VD group was significantly lower than that in the control group. These findings suggest that the phenotype of ApoE is associated with DAT and VD, and that the lower level of ApoE mRNA may play an important role in the development of DAT as well as VD.     

脂蛋白(a)在不同部位脑梗死病人中的诊断价值

目的：探讨高浓度Ｌｐ（ａ）在不同部位脑梗死的关系。方法：采用单向火箭免疫电泳法检测６０例健康人和６６例脑梗死患者血清Ｌｐ（ａ）的含量。结果：脑梗 皮质动脉区脑梗死组Ｌｐ（ａ）水平显著性地高于对照组，其中穿通动脉区脑梗死组Ｌｐ（ａ）含量明显低于皮质动脉区脑梗死组，而与正常对照组无显著性差异，结论：血清Ｌｐ（ａ）浓度增高是脑梗死重要的危险因素，其中可能在在皮质动脉区脑梗死发病中起到独立的作用。     

中青年人脑卒中与血脂关系的研究

目的 探讨血脂与中青年人脑卒中的关系。方法 检测了206例中青年脑卒中患者及80例对照者的甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL－C）、低密度脂蛋白胆固醇（LDL－C）、载脂蛋白A－I（ApoA-I)、载脂蛋白B100（ApoB100)和脂蛋白（a)[Lp(a)]血清含量。结果 脑梗死组TG、TC、LD-L－C、ApoB100及Lp(a)水平显著高于对照组,Lp(a)水平亦高于脑出血组,异常的血脂成分随年龄变化而发生改变;皮层动脉区脑梗死组Lp(a)水平显著高于穿通动脉区脑梗死组;脑出血组血脂指标与对照组比较差异无显著。结论 血脂代谢紊乱是中青年人脑梗死的危险因素。     

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.     

阿尔茨海默氏病与血管性痴呆临床特点的对照研究

目的比较阿尔茨海默氏病（AD）与血管性痴呆（VD）的临床特点。方法对39例AD和38例VD患者的精神行为症状特点、伴随的躯体疾病、头颅CT检查以及脑电图检查进行比较。结果AD组与VD组在幻觉、妄想等精神病性症状方面无明显差异,在抑郁、焦虑等情绪障碍以及行为脱抑制方面有显著差异;AD组伴随的躯体疾病无明显特异性,VD组多伴发高血压、冠心病;AD组头颅CT多表现为脑萎缩,VD组多表现为脑梗塞;脑电图检查AD组无明显特异性,VD组界限脑电图居多。结论AD与VD患者的BPSD及所伴随的躯体疾病可有不同特点,CT和脑电图的检查等对痴呆的诊断与鉴别诊断均具有重要价值。     

脑梗塞合并冠心病36例临床分析

本文报告36例脑梗塞合并冠心病,其中男26例,女10例,脑梗塞合并心绞痛16例,心肌梗塞7例,隐性冠心病13例,死亡10例,主要死因有心力衰竭、肾功能衰竭、脑水肿并脑疝。对脑梗塞与冠心病同时存在的病理生理机制进行了讨论。为了提高诊疗水平,作者强调详细询问病史、认真体查、及时监测心脑功能和二病同治的原则,并应积极消除致病因素。     

Possible antidepressant dihydroergosine preferentially binds to 5-HT1B receptor sites in the rat hippocampus

Summary Cerebrospinal fluid (CSF) and serum levels of 22 amino acids were studied in 13 patients with dementia of the Alzheimer type (DAT), 13 patients with vascular dementia (VD) and 15 age-matched controls. We found significantly reduced levels of glutamate in CSF samples from DAT patients compared to VD and control subjects, but CSF levels of aspartate were found to be significantly elevated in the two groups of dementia studied. Moreover, CSF concentrations of tyrosine, leucine and phenylalanine were significantly increased in VD patients in comparison with those in DAT patients and control subjects. Our results showed a wide increase in CSF/serum amino acid ratios in DAT and VD groups compared to controls. However, no differences were found in CSF/serum ratios between dementia groups. These changes show evidence for a possible disorder of amino acid metabolism with different patterns in these two dementia types.     

Lipoprotein(a) as a strong indicator for cerebrovascular disease

To evaluate the role of lipoprotein(a) (Lp(a] in patients with cerebrovascular disease (CVD), lipid parameters were compared with a control group (CO). Additionally, the Lp(a) serum levels were investigated in a coronary artery disease (CAD) group. The CO was made up of 37 healthy persons (age: 54.5 +/- 7.7, 26 males and 11 females), the CVD group included 46 patients with sustained transient ischemic attack (TIA) prolonged reversible ischemic neurologic deficits (PRIND) and cerebral infarction (CI) (age: 53.6 +/- 9.7, 32 males and 14 females), and the CAD group was made up of 28 survivors of myocardial infarctions (age: 52.5 +/- 8.1, 18 males and 10 females). The median values of Lp(a) in CVD were significantly higher than in the CO (p less than 0.01) and did not differ significantly from the CAD. Total TC, HDL-C, TG, LDL-C and the ratio of LDL-C/HDL-C did not show any significant difference between the control and cerebrovascular disease group. For quantification of the vascular lesions of the carotid system, a Duplex Doppler score system was used. The score correlated with Lp(a) in patients between 40 to 65 years of age (r = 0.34, p less than 0.01). Thus, we conclude that Lp(a) is not only a risk factor for CAD but also for CVD.     

Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients.

CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.     

LIPOPROTEIN(a) CONCENTRATION AND MOLECULAR WEIGHT OF APOLIPOPROTEIN(a) IN PATIENTS WITH CEREBROVASCULAR DISEASE AND DIABETES MELLITUS

Plasma lipoprotein(a) [Lp(a)] concentrations are genetically determined, and hyper-Lp(a)-emia is an independent risk factor for atherosclerosis and thrombosis. To study the implications of Lp(a) in cerebrovascular disease (CVD) and diabetes mellitus (DM), we examined plasma Lp(a) levels and molecular weights of apolipoprotein(a) [apo(a)] in 118 patients with CVD, and 125 cases with DM. Although mean Lp(a) concentrations were higher in those cases with atherothrombotic brain infarction than in those with brain hemorrhage and lacunar infarction, the difference was not statistically significant. Lp(a) levels were significantly higher in the DM cases treated with insulin and in those treated with oral hypoglycemic agents than in those on diet therapy alone, suggesting that insulin and oral agents modulate apo(a) expression. Lp(a) concentrations correlated significantly with the low-molecular-weight isoforms of apo(a) in all CVD and DM groups. © 1997 Elsevier Science Ltd     

对97例脑梗塞后痴呆的危险因素分析

目的 探讨脑梗塞后血管性痴呆（ＶＤ）的发生率及其危险因素。方法 采用简易智力状态检查表（ＭＭＳＥ）和流调用抑郁自评量表（ＣＥＳ－Ｄ）;对９７例住院脑便塞病人进行筛选与检测。对其中认知受损者则采用日常生活能力量表（ＡＤＬ）和Ｈａｃｈｉｎｃｋｉ缺血指数量表（ＨＩＳ）进上步检测。并对痴呆组５和非痴呆组病人的临床资料进行统计分析。结果 （１）２７例确诊为ＶＤ,ＶＤ发生率为２７．８４％,≥６５岁为３４．３３     

Optico-cerebral syndrome: simultaneous hemodynamic infarction of optic nerve and brain

Three (0.5%) of 612 patients with an acute ischemic stroke in the carotid territory also had ipsilateral optic nerve infarction. They had unilateral or bilateral internal carotid artery occlusion and reversed flow in the ophthalmic artery. Hemodynamic infarction was suggested by triggering by a drop in blood pressure, decreased ophthalmic artery flow and perfusion pressure, and cerebral infarction in a watershed area. The "optico-cerebral syndrome" suggests internal carotid artery occlusion with hemodynamic disturbances. In carotid disease, monocular blindness may be due to an optic nerve lesion sparing the retina.     

Vascular risk factors in demented elderly: analysis of Alzheimer Clinic materials]

In recent years evidence is increasing that vascular disease is associated with cognitive impairment and dementia. Moreover, presence of cerebrovascular disease may intensify the clinical symptoms of Alzheimer's disease (AD). The aim of the study was to determine the prevalence of vascular risk factors in age and sex matched patients with dementia. We studied 109 patients with AD and 37 patients vascular dementia (VD). DSM-III-R test for dementia, NINCDS-ADRDA guidelines for AD and NINDS-ARIEN for VD were applied. RESULTS: Mean age of dementia onset in AD and VD was 65.8 SD 7.8 and 67.4 SD 7.0 years (p > 0.05), the duration of dementia, MMS and GDS for patients with AD and VD was not significantly different. Arterial hypertension was associated in 51.3% VD and 30.3% AD (p < 0.05), hypotension in 11.1 and 23.6% respectively (p > 0.05), atrial fibrillation was similar in AD and VD, coronary artery disease was presents 64.8% AD and 46.8 VD (p > 0.05) and type 2 diabetes in 21.6% and 10.1% (p > 0.05) respectively. No significant differences in serum lipid profile were found in both groups, except two times higher incidence of normal HDL-cholesterol concentration in AD compare to VD. The relation between alcohol consumption, cigarette smoking and head trauma was similar in both types of dementia. CONCLUSION: Vascular disease and AD have to some extent a shared aetiology, and risk factors that they have in common increase the risk of both disorders independently and vascular disease is perhaps involved in the aetiology of AD.     

听觉P300对血管性痴呆早期诊断及鉴别诊断的价值

目的探讨P300对血管性痴呆(VD)的早期诊断及与Alzheimer病(AD)鉴别的价值.方法分别对20名正常人(NC)、20例VD患者、24例无痴呆脑梗死患者(CI)及20例AD患者进行神经心理学量表长谷川智力量表(HDS)评分,并选用听觉oddball序列分别对上述各组进行P300测试.结果 (1)VD组与CI组及NC组比较,N2、P3潜伏期(PL)明显延长(均P<0.05);P3PL与HDS评分呈负相关(r=-0.686,P＜0.01),且较HDS更为敏感;梗死部位与P300变化有一定关系,梗死位于颞叶、额叶的患者与其他梗死部位的患者相比,P3PL异常率明显增高(P＜0.05).(2)AD组与VD组相比,N1 PL更长,差异有显著性(P<0.05).结论 (1)P300对VD的早期诊断具有重要意义.(2)N1PL在VD与AD的鉴别诊断中有一定的意义.     

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     

交界区脑梗死与脑动脉狭窄或闭塞的关系

目的　观察交界区脑梗死与颅内外主要动脉狭窄或闭塞的关系。方法　回顾性分析经磁共振(MRI)弥散加权成像 (DWI)检查证实的急性交界区脑梗死 4 5例患者的临床资料 ,将交界区梗死部位分为前交界区、后交界区及内交界区 ,利用磁共振血管成像 (MRA)和经颅超声多普勒 (TCD)检查判断颅内外主要动脉有无狭窄或闭塞 ,观察梗死部位与血管受累的情况。结果　 4 5例中共有 32例 (71 1% )存在相应血管狭窄或闭塞。大脑中动脉狭窄出现比例最高 (4 7 6 % ) ,其次为颈内动脉狭窄或闭塞 (31% ) ,大脑前或后动脉狭窄少(11 9% )。动脉异常情况在单交界区与多交界区梗死的患者间无差别 ,但内交界区受累更易合并大脑中动脉狭窄 (P <0 0 5 )。结论　交界区脑梗死患者常存在颅内外主要动脉狭窄或闭塞 ,大脑中动脉狭窄最常见 ,尤其在内交界区受累时。     

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.