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1.
2型糖尿病可能加重颈动脉斑块的易损性并增加缺血性中风的风险,关于2型糖尿病患者伴有颈动脉斑块特征的急性中风亚型鲜有研究报道。本研究旨在探讨2型糖尿病患者颈动脉斑块特征与MRI确定的急性脑梗死病变特征之间的关系。本研究以颈内动脉区急性脑血管病患者为研究对象,所有患者分为2型糖尿病组和非2型糖尿病组,分别行颈动脉和脑部MRI扫描,测定同侧颈动脉斑块的形态和特征,以及颅内和颅外颈动脉狭窄。基于中风亚型和急性脑梗塞病变模式对患者进行评估。研究结果表明,与非2型糖尿病患者相比,2型糖尿病患者颈动脉型IV-VI病变的患病率更高,斑块负荷更大,以及富脂质坏死核(LRNC)更大。在有症状的颈动脉LRNC患者中,与非2型糖尿病组相比,2型糖尿病组颈内动脉区出现较多的伴有大穿孔动脉梗塞形态和较大的急性脑梗塞。LRNC%>23.5%的颈动脉斑块是2型糖尿病患者存在颈动脉狭窄的急性脑梗塞病变的独立危险因素。颈动脉斑块特征的量化,尤其是MRI诊断的富脂质坏死核对中风风险具有潜在应用价值。  相似文献   

2.
The purpose of this investigation was to determine the atherosclerotic changes in patients with vascular parkinsonism and in patients with idiopathic Parkinson's disease, in order to evaluate the possible influence of the extracranial pathology of carotid arteries in developing lacunar cerebral infarcts. Degree of stenosis and plaque morphology of the extracranial part of carotids in both group of patients were evaluated by color Doppler flow imaging ultrasound investigation and the results were compared. We selected two matched groups of patients with parkinsonism: 22 patients with vascular parkinsonism, and 28 with idiopathic Parkinson's disease.The atherosclerotic changes found in patients with Parkinson's disease showed mild carotid lesions with mostly stable calcified plaques and lesser risk for embolic cerebral intravascular events contrary to the higher degree of carotid stenosis found in patients with vascular parkinsonism with mostly mixed plaques prone to embolization. Therefore, we suggest performing ultrasonographic examination of the extracranial part of carotid arteries in all patients with parkinsonism to assess risk of vascular accidents originating from carotid lesions. That would enable adequate treatment of parkinsonism and prevent further occurrence of intracranial vascular changes.  相似文献   

3.
目的研究脑卒中患者血管危险因素与颈动脉粥样硬化的关系。方法受试者151人主要为脑梗死及椎-基底动脉供血不足病例。将所有受试对象行颈动脉超声检查,采用二分类变量的Logistic回归分析方法对其危险因素进行筛选,找出与颈动脉粥样硬化改变相关的因素。结果年龄及吸烟与颈动脉内中膜增厚之间存在相关性,P=0.006(OR=1.08,95%CI 1.02-1.14)和0.01(OR=5.09,95%CI 1.47-17.61);年龄、吸烟同样与颈动脉斑块之间存在相关性,P=0.006(ORn=n1.06,95%CI 1.06-1.11)和0.04(ORn=2.97,95%CI 1.04-8.50),收缩压与颈动脉斑块呈正相关,P=0.04(OR=1.03,95%CI 1.00-1.05),舒张压与颈动脉斑块呈负相关P=0.04(OR=0.96,95%CI 0.92-1.00)。结论随年龄的增大动脉内中膜增厚及颈动脉斑块的患病率增加,吸烟者内中膜增厚及颈动脉斑块比率高于不吸烟者;收缩压增加颈动脉斑块患病率增加,舒张压增加斑块患病率下降。  相似文献   

4.
目的:探讨不同部位脑梗死导致血管性痴呆的脑电图表现差异,为血管性痴呆的诊断分类提供客观依据。方法:80例诊断血管性痴呆的患者根据影像学表现分为多灶梗死后痴呆和关键部位梗死后痴呆。入选患者均于饱餐后2小时给予常规18导脑电图检查,记录时间为30分钟以上。结果:1多灶梗死后痴呆多表现为α节律减慢,6-8Hz为主;波幅低,以20-25Uv为主,α波频率调节差、节律不规则。低波幅θ波出现者27例,占71.1%,出现于各导联,出现δ波者17例,占44.7%。2关键部位梗死后痴呆的患者中,正常为6例,占13%。异常者39例,占87%。EEG改变主要表现为α指数减少,节律以7-9Hz为主的患者28例,占71.8%。低波幅θ波出现者17例,以前额为主,占43.6%。39例患者未出现δ波。结论:不同部位梗死后血管性痴呆的脑电图表现不尽相同,可以为血管性痴呆的分类诊断提供客观依据。  相似文献   

5.
Stereological investigations (Leitz-Classimat) of the capillary net of young (19-44 yrs), old (85-95 yrs) and age-matched demented patients with Alzheimer's disease show a condensation (40%) of the capillary volume in the cerebral cortex of the Alzheimer group (n-3) compared with the age-matched controls (n-7), without change of the capillary diameter. These results represent gross atrophy of the frontal brain in senile dementia of Alzheimer type (SDAT). No changes of this kind can be observed between young individuals (n-6) and normal aged group. The behaviour of the capillary net in the putamen is different from that of the cortex. Already during normal aging a 80% condensation of the capillary volume is observed (capillary volume and length per unit increase, intercapillary distances decrease). A comparison between the aged group and the Alzheimer patients exhibits neither additional alterations of capillary parameters nor decreased volume of the putamen. In all anatomical layers of the frontal cortex a significant atrophy (27-36%) of neuronal perikarya (size and shape measurements with the TAS of Leitz) occurs in the Alzheimer group, compared with the normal aged ones. In the same way, neuronal surface area decreases by 30% in the putamen. Significant changes of perikaryal shape in both brain regions confirm marked neuronal atrophy in Alzheimer's disease. During normal aging only 85-95 years old group shows significantly smaller (15-35%) neurons in comparison to young individuals. Quantitative image analysis facilitates considerably evaluating new morphometrical data of the aging process in the human brain, which are important for a pharmacological concept of treating cerebral insufficiency symptoms.  相似文献   

6.
颈动脉负压分流制作大鼠全脑缺血/再灌注模型   总被引:13,自引:0,他引:13  
目的 根据解剖学和血流动力学原理建立新型大鼠全脑缺血/再灌注模型。方法 夹闭大鼠双侧颈总动脉,同时经右颈外动脉持续抽吸颈总动脉内血液,造成大鼠全脑缺血,抽出的血液从左股静脉回输;停止抽吸血液,去除微动脉夹,开始再灌注。应用脑电图、光镜和电镜等评定脑缺血的效果。结果 实验组大鼠脑电图、光镜和电镜检查均显示明显的缺血改变。结论 本模型具有全脑缺血效果可靠、再灌注充分、制备简便、成功率高并可经颈动脉注入药物等优点,适用于全脑缺血/再灌注损伤及其干预措施的实验研究。  相似文献   

7.
OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.  相似文献   

8.
The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker N(G)-nitro-L-arginine methyl ester (L-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, L-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after L-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.  相似文献   

9.
目的:探讨螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。方法:选取2014年1月至2016年1月期间来我院就诊的60例急性脑梗死患者作为观察组,另选同期来我院就诊的非急性脑梗死患者60例作为对照组。两组患者均进行螺旋CT头颈部血管成像检查,比较两组患者的颈动脉狭窄程度及各段血管斑块分布情况,并根据检查结果评价螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。结果:观察组轻度狭窄与中度狭窄检出率均显著高于对照组(P0.05),重度狭窄与闭塞检出率与对照组比较无统计学差异(P0.05),观察组总检出狭窄率高于对照组(P0.05)。观察组与对照组在颈动脉分叉处、颈总动脉、颈内动脉及颈外动脉均有斑块检出,观察组斑块总检出率为69.4%,显著高于对照组的41.2%(P0.05)。结论:临床上应用128层螺旋CT头颈部血管成像技术对急性脑梗死患者颈动脉狭窄情况可进行有效评估,该方法对患者轻、中度狭窄以及双侧颈动脉斑块检出率更高,在临床诊断及预后防治中具有应用推广价值。  相似文献   

10.
Vascular cognitive impairment and dementia (VCID) is the most common etiology of dementia in the elderly. Both, vascular and Alzheimer’s disease, pathologies work synergistically to create neurodegeneration and cognitive impairments. The main causes of VCID include hemorrhage/microbleed (i.e., hyperhomocysteinemia), cerebral small vessel disease, multi-infarct dementia, severe hypoperfusion (i.e., bilateral common carotid artery stenosis), strategic infarct, angiopathy (i.e., cerebral angiopathy), and hereditary vasculopathy (i.e., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). In this review, we will discuss the experimental animal models that have been developed to study these pathologies. We will discuss the limitations and strengths of these models and the important research findings that have advanced the field through the use of the models.  相似文献   

11.
Patients with spinocerebellar ataxia type 3 (SCA3) have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE) and electroencephalography (EEG), are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD) method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA), the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients’ MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.  相似文献   

12.
目的:研究血管内皮功能与颈动脉内膜中膜厚度在监测和评估糖尿病肢动脉闭塞症病情变化中的作用及临床意义。方法:将2012年10月至2013年10月入院的75例糖尿病肢体动脉闭塞症患者为研究对象,按照病程分为一、二和三期组,各25例,并纳入25例健康者为对照组。测定其体内一氧化氮、内皮素1、6-酮-前列腺素F1a和血栓素B2水平变化,并运用高分辨率超声对患者及对照组颈动脉内膜中膜厚度(IMT)、内皮依赖性舒张功能(EDD)及非内皮依赖性舒张功能(EID)进行检测,分析比较各组间差异性。结果:随着病程变化,健康对照组与三组糖尿病肢体动脉闭塞症患者相比较高,一、二和三期患者的EDD逐渐降低,且差异有统计学意义(P0.01)。三期患者的EID值较健康组、一期及二期患者低,差异有统计学意义(P0.01)。二期与三期患者IMT与对照组相比逐渐升高,差异有统计学意义(P0.01)。各病程糖尿病肢体动脉闭塞症患者的总胆固醇水平、空腹血糖水平、收缩压及舒张压均高于健康对照组(P0.05),而各组间差异无统计学意义。结论:血管内皮功能及颈动脉内膜中膜厚度的变化可反映糖尿病肢体动脉闭塞症的病程发展,可作为这临床诊断与监测的参考指标。  相似文献   

13.
We studied the hexose transporter protein of the frontal and temporal neocortex, hippocampus, putamen, cerebellum, and cerebral microvessels (which constitute the blood-brain barrier) in Alzheimer disease and control subjects by reversible and covalent binding with [3H]cytochalasin B and by immunological reactivity. In Alzheimer disease subjects, we found a marked decrease in the hexose transporter in brain microvessels and in the cerebral neocortex and hippocampus, regions that are most affected in Alzheimer disease, but there were no abnormalities in the putamen or cerebellum. Hexose transporter reduction in cerebral microvessels of Alzheimer subjects is relatively specific because other enzyme markers of brain endothelium were not significantly altered. The low density of the hexose transporter at the blood-brain barrier and in the cerebral cortex in Alzheimer disease may be related to decreased in vivo measurements of cerebral oxidative metabolism.  相似文献   

14.
In this study we evaluated the adenosine stress-test combined with 99mTc-HMPAO SPECT as a possible tool for evaluation of brain perfusion reserve in patients with various degrees of cortical neurologic damage due to internal carotid artery stenosis. The investigation comprised 37 patients with atherosclerotic carotid disease, in everybody of whom the stenosis was detected by echo-Doppler study of carotids and later in 28 verified also using invasive intraarterial digital subtractive angiography. In everybody the 99mTc-HMPAO SPECT study was performed twice: at rest and during stress-test with intravenous injection of adenosine with the patient in the supine position. It was gathered three groups of patients with different kinds of cerebral blood flow reactivity in adenosine stress-test. Henceforth, we conclude that, first, the 99mTc-HMPAO SPECT adenosin stress challenge of cerebral blood flow is a reliable functional test for every group of patients with extensive atherosclerosis and can be used for detection of patients with exhausted or decreased cerebral perfusion reserve in whom the risk of future cerebral vascular ischaemic events is elevated.  相似文献   

15.
Twelve healthy pregnant women were studied between 35 to 40 weeks gestation to determine the effect of carbon dioxide on the Doppler flow velocity waveform in the cerebral and umbilical arteries of the human fetus near term. The Resistance index (RI), as an index of vascular resistance, was calculated for the internal carotid and umbilical arteries during a control period while patients breathed room air followed by three randomized 15-30 min study periods with patients breathing either room air, a prepared gas mixture with 2% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The RI of the internal carotid and umbilical arteries both showed a significant inverse relationship to maternal end-tidal PCO2 with a greater negative slope for RI plotted against end-tidal PCO2 in the internal carotid artery (0.0153) than in the umbilical artery (0.0047). The change in the RI as an index of changing vascular resistance, suggests that carbon dioxide is also an important determinant of cerebral blood flow in the human fetus, as previously described for fetal sheep, with a lesser although significant effect on umbilical blood flow.  相似文献   

16.
OBJECTIVE: To determine the safest, least costly, and most effective way to select patients with symptomatic carotid ischaemic events for carotid angiography before carotid endarterectomy. DESIGN: Prospective cohort study. SETTING: University departments of clinical neurosciences and clinical neurology. PATIENTS: 485 Patients with carotid territory transient ischaemic attacks of the brain (n = 224) or eye (n = 162) or retinal infarction (n = 99) were referred to a single neurologist between 1976 and 1986. INTERVENTIONS: Clinical examination by auscultation over the precordium, supraclavicular fossae, and neck vessels (all patients). Cerebral angiography of patients suitable for carotid endarterectomy. MAIN OUTCOME MEASURES: Financial cost and number of disabling strokes after angiography. RESULTS: 296 Patients were investigated by cerebral angiography. Ischaemic symptoms had occurred in the distribution of 298 internal carotid arteries (symptomatic) that were imaged, two patients having bilateral symptoms. The presence or absence of a carotid bruit and the maximum percentage diameter stenosis of the origin of the symptomatic internal carotid artery were correlated. The prevalence of mild disease (diameter stenosis greater than or equal to 25%) of the symptomatic internal carotid artery was 57%, and if an ipsilateral carotid bruit was heard the probability of mild stenosis rose to 92%. The prevalence of moderate disease of the symptomatic internal carotid artery (stenosis greater than or equal to 50%) was 39%, and if a bruit was heard the probability doubled to 78%. The prevalence of severe internal carotid disease (stenosis greater than or equal to 75%) was 22%, and if a bruit was heard the probability was more than double, at 49%. The direct cost to both the NHS and the private health sector of investigating patients with symptomatic carotid ischaemia was estimated for several strategies of carotid artery imaging and expressed in terms of financial cost and number of strokes after angiography incurred in detecting all patients with diameter stenosis of the symptomatic internal carotid artery of greater than or equal to 25%, 50%, or 75%. To detect diameter stenosis of the internal carotid artery of greater than or equal to 25% it is most cost effective to proceed directly to cerebral angiography in patients with a carotid bruit over the symptomatic carotid bifurcation and to screen patients without a carotid bruit by duplex carotid ultrasonography; patients in whom duplex ultrasonography discloses stenosis of greater than or equal to 25% are then referred for cerebral angiography. To detect only more severe internal carotid disease (stenosis of greater than or equal to 50%) the same policy applies, unless the local duplex ultrasonographic service is particularly efficient and reliable, when it is probably most cost effective and safer to screen all patients by this method irrespective of the findings on cervical auscultation. To detect stenosis of 75% or greater it is most cost effective to screen all patients with duplex ultrasonography, whether a carotid bruit is present or not, because this approach reduces the number of angiograms required, is the least expensive, and results in the least number of strokes after angiography. CONCLUSIONS: Patients selection for cerebral angiography before carotid endarterectomy needs to be appropriate and cost effective. Sound clinical evaluation and duplex carotid ultrasound are required. The findings of this study should not be applied to other medical centres without first considering possible differences in the prevalence of carotid artery disease, the efficiency and reliability of duplex ultrasonography, the local complication rates of cerebral angiography, and the local costs of the imaging procedures.  相似文献   

17.
Abstract: Lysosomal hydrolases are normally intracellular enzymes but are abundant extracellularly within senile plaques in Alzheimer disease and in other conditions where β-amyloid accumulates. To examine whether acid hydrolases released from abnormal hydrolase-laden neurons are detectable in CSF, we measured levels of the major aspartic proteinase of lysosomes, cathepsin D (Cat D), in ventricular CSF collected after death from 30 patients with Alzheimer disease, 14 patients with Huntington disease, and seven patients with other neurodegenerative diseases. The levels of Cat D-immunoreactive protein, expressed as micrograms per milliliter of protein, determined by western blot immunoassay using a polyclonal antiserum against human brain Cat D, were more than fourfold higher in the Alzheimer patients than in the other patient groups ( p < 0.0005). Cat D activity, assayed separately against [14C]methemoglobin at pH 3.2, was also significantly elevated but less than Cat D content. The lower specific activity of Cat D in Alzheimer CSF therefore indicated that the abnormally accumulated Cat D included a high proportion of inactive enzyme. These results indicate that abnormal Cat D release from affected neurons into the extracellular space is an active, ongoing process in Alzheimer brain. In addition, the levels of this enzyme and possibly other lysosomal hydrolases in CSF may prove to be useful biological markers of Alzheimer disease.  相似文献   

18.
beta-Endorphin-like immunoreactivity in cerebrospinal fluid(CSF) was observed to decrease in patients with Huntington's disease and dementia due to brain vascular disease. The greatest decrease was seen in patients with presenile and senile dementia of Alzheimer type(SDAT). The immunoreactivity significantly correlated with psychological functions when examined using a dementia rating scale (r=0.51, p less than 0.01, for all dementia, r=0.65, p less than 0.02, for only SDAT). These results suggest that a B-endorphin-like substance may be related in the pathophysiology of dementia.  相似文献   

19.
The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.  相似文献   

20.
The exact cause of Alzheimer’s disease and the part played in it by aluminum is still speculative. We have studied serum aluminum in 356 healthy people, and we have observed that serum aluminum concentration is increased in aging people in relation to age. We suggest that this could be associated with an enhanced gastric permeability or by an increase in metal accumulation proportional to age. We have measured serum aluminum levels in patients with probable Alzheimer’s disease, patients with other senile dementias, and agematched group. Patients with probable Alzheimer’s disease have statistically significant higher serum aluminum levels than patients with other types of senile dementias (alcoholic, vascular, multi-infart) and an age-matched control group. When we compare serum aluminum of patients with senile dementias from other causes with the agematched control group, we do not find significant differences.  相似文献   

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