CT in the differential diagnosis between Alzheimer''s disease and vascular dementia

A prospective series of consecutively admitted patients with Alzheimer's disease (AD) (n = 68), multi-infarct dementia (MID) (n = 79) and probable vascular dementia (PVD) (n = 46) were studied by CT of the head. In MID 88.6% and in PVD 41.3% of the patients had at least one brain infarct on CT, but only one patient (1.5%) with AD. White matter low attenuation (WMLA) also differentiated MID and PVD from AD, especially among patients aged 75 years or less, and with mild or moderate dementia. In all types, brain atrophy on CT had a positive correlation with the degree of dementia. Infarcts and WMLA on CT, but not brain atrophy seem to be of differential diagnostic value between vascular and degenerative dementia.     

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.     

Relationship between vascular factors and white matter low attenuation of the brain

To study the relationship between vascular factors and white matter low attenuation of the brain (WMLA), computer tomography findings of 251 patients were re-interpreted. Clinical data on patients were collected from the hospital records. It was possible to obtain sufficient clinical data on 204 patients who were included in the study. WMLA changes, on computer tomography, were found in 51.5% of patients. WMLA was most commonly present in patients with vascular (69.8%) and combined (69.2%) dementia. The occurrence of WMLA did not differ between patients with Alzheimer's disease (26.7%) and those without dementia (35.9%). Arterial hypertension, coronary heart disease, or diabetes were not associated with WMLA. Heart failure and orthostatic hypotension, were found to be more commonly present in patients with than in those without WMLA more commonly present in patients with than in those without WMLA (34.0% vs 14.3%, p = 0.0012; 10.0% vs 2.0%, p = 0.036). Both systolic and diastolic low blood pressure values were associated with WMLA unlike hypertensive blood pressure values. Atrial fibrillation in electrocardiography was associated with WMLA, while neither left ventricular hypertrophy nor myocardial infarction was. When several explanatory variables were adjusted by logistic regression analysis, age, heart failure, and systolic blood pressure below 130 predicted WMLA. In conclusion, the association between WMLA and vascular factors with hemodynamic significance suggests that cerebral hypoperfusion may contribute to the genesis of WMLA.     

Oligoclonal immunoglobulin bands in cerebrospinal fluid of patients with Alzheimer''s disease and vascular dementia

We examined serum and cerebrospinal fluid (CSF) of 16 patients with Alzheimer's disease (AD), 28 patients with vascular dementia (VD), their age-matched controls and multiple sclerosis (MS) patients in order to evaluate the humoral immune response within the central nervous system both quantitatively and qualitatively. Intra-blood-brain barrier (BBB) protein synthesis was calculated by CSF IgG index. The presence of oligoclonal banding (OCB) was investigated with agarose isoelectric focusing (IEF) followed by immunoblotting with antihuman IgG. No patient with AD and only 4 patients with VD had slightly elevated IgG indexes, and no statistically significant differences in the indexes were found between the two groups. No bands were found in the CSF of AD patients but 3 VD patients had OCB in both serum and CSF. One VD patient had bands in serum but no bands in CSF. No kappa or lambda free light chains were found in those demented patients with demonstrable bands in the CSF and serum. No OCB were found in control sera and CSF. For comparison, the majority of patients with MS had OCB in CSF. Thus, no consistent increase of intrathecal protein synthesis was found in patients with AD and VD. Methodological differences explain at least part of the conflicting results published earlier.     

Neuropsychological differentiation between normal aging, Alzheimer''s disease and vascular dementia

A random sample of 182 elderly community residents and 211 demented patients were studied using the D-Test Battery based on the Luria's neuropsychological investigation method. A steady but selective cognitive impairment was observed with increasing age in normal healthy subjects. The most sensitive areas of cognition to the effects of normal aging were mnestic and conceptual functions, as well as arithmetical skills. The age-related changes could be clearly differentiated from the changes found in patients with mild degree of dementia. The test also differentiated patients with mild, moderate and severe dementia from each other on the basis of their social competence. It failed to demonstrate specific patterns of impairment and to clearly differentiate between patients with Alzheimer's disease and vascular dementia who had the same degree of cognitive decline. Further qualitative analyses are needed to improve the sensitivity and specificity of the test.     

White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study

White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction.     

EEG in the differential diagnosis between Alzheimer''s disease and vascular dementia

Demented patients with Alzheimer's disease (AD) (n = 67), multi-infarct dementia (MID) (n = 77) and probable vascular dementia (PVD) (n = 45) were studied with electroencephalography (EEG). All patients underwent a routine EEG examination and quantitative EEG was recorded from 14 patients with AD, 20 with MID, and 12 with PVD. The patient groups did not differ in regard to sex, age, education, or degree of dementia. Diffuse abnormality of EEG increased in AD, while driving response to photic stimulation and the mean frequency of background activity decreased in all groups with increasing degree of dementia. In quantitative EEG, the percentage of alpha power decreased and those of theta and delta power increased relative to the degree of dementia. Focal abnormalities, and irritative (spikes and/or sharp waves) and slow wave paroxysms were more common in MID than in AD. Patients with different types of dementia did not differ significantly in regard to diffuse abnormality, occurrence of driving response, mean background frequency, or parameters of quantitative EEG. The mean frequency of background activity and the degree of diffuse abnormality correlated with central and cortical atrophy, white matter low attenuation seen on computed tomography, and with neuropsychological findings.     

Alzheimer病与血管性痴呆患者认知功能对照研究

目的探讨Alzheimer病与血管性痴呆患者认知功能状况及其之间差异。方法对36例临床诊断的Alzheimer病、35例血管性痴呆患者及35例健康人进行了事件相关电位(ERP)和简易智力状态检查(MMSE)测试。结果Alzheimer病组、血管性痴呆组ERP测定的异常率为94.4%(34/36)和85.7%(30/35),两组ERP中N2、P3波潜伏期较正常对照组延长,P3波幅降低,其差异具有统计学意义(P<0.01);而Alzheimer病组ERP测定N2、P3波潜伏期较血管性痴呆组延长,P3波幅降低,其差异具有统计学意义(P<0.05)。Alzheimer病组、血管性痴呆组MMSE量表总分值与分量表得分值较正常组降低,差异具有统计学意义(P<0.01,P<0.05);Alzheimer病组与血管性痴呆组比较,在MMSE量表总分、时间定向及物体命名等分值明显降低,差异具有统计学意义(P<0.05)。结论Alzheimer病与血管性痴呆患者均存在明显的认知功能减退,且Alzheimer病认知损害更为明显。     

Regional differences in diffusion abnormality in cerebral white matter lesions in patients with vascular dementia of the Binswanger type and Alzheimer's disease

We investigated changes in water diffusion in the cerebral white matter of 14 patients with vascular dementia of the Binswanger type (VDBT) and ten patients with Alzheimer's disease (AD) with periventricular hyperintensity (PVH) lesions using diffusion-weighted magnetic resonance imaging (MRI) and studied the pathophysiological differences between white matter lesions found in these two conditions. Apparent diffusion coefficients (ADCs) in the anterior and posterior white matter and the genu and splenium of the corpus callosum were significantly higher in both groups of patients than in the 12 age-matched controls, and ADC values in VDBT and AD groups were almost the same. ADC ratios, defined as diffusion restricted perpendicular to the direction of nerve fibers, were also significantly higher in the patients than in the control subjects. However, there were regional differences in ADC ratios in the two conditions, with ratios in VDBT being higher in the anterior portions of the white matter but ratios in AD were higher in the posterior portions. The diffusion-weighted MRI technique may be useful in the differential diagnosis of VDBT and AD with white matter lesions.     

Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia

The prevalence of Alzheimer's disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE₂ offers protection and apoE₃ is neutral, while apoE₄ promotes the development of the disease. Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD. Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates. In our results, we found that most of the patients with AD had the apoE4 isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 ± 0.89, VAD: 6.3 ± 0.8, AD: 6.52 ± 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 ± 0.6, VAD: 3.96 ± 0.8, AD: 3.84 ± 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 ± 55 U/l; AD: 131 ± 37, VAD: 151 ± 50 l; p < 0.05). Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimer's disease and vascular dementia. Received: 30 November 2001 / Accepted: 24 January 2002     

Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia

OBJECTIVES: The study aimed to increase understanding of behavioural changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). METHODS: A semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD patients. RESULTS: Behavioural changes that strongly discriminated FTD from AD and to a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies, loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of patients using regression analysis. CONCLUSIONS: Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion.     

Survival and cause of death in Alzheimer''s disease and multi-infarct dementia

Survival and causes of death of 218 patients with Alzheimer's disease (AD) and of 115 patients with multi-infarct dementia (MID) were examined. The patients were originally found in a community-based epidemiological survey of dementia, and all patients with AD or MID alive on the prevalence day were included. The 6-years survival rate for AD was 21.1% vs. the expected rate 48.5%, that for MID 11.9% vs. 45.2% expected. A comparison of relative survival rates suggested that MID carries a less favorable survival prognosis than AD. The mean durations were: AD 5.7 years and MID 5.2 years; median duration being 5 years in both diseases. The excess mortality in both AD and MID was independent of age. In AD, the survival rate decreased with increasing severity of dementia, while in MID the mortality was the same regardless of the severity of the dementia. The dementia disorder was the underlying cause of death in 68% of AD patients, and in 38% of MID patients, bronchopneumonia being the most frequent immediate cause of death in both groups. As a cause of death, acute cerebrovascular accidents occurred more often in MID patients than in the general population of comparable age. Malignant diseases were less frequent as a cause of death in both dementia groups than in the general population.     

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。     

White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia

OBJECTIVE: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.     

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.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the Abeta(42) species were by far the predominant form of extractable peptide compared with Abeta(40) peptide in VaD brains. The strong signal intensity for the peak representing Abeta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both Abeta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Abeta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.     

皮质下缺血性血管性痴呆患者认知功能与脑白质弥散张量成像的关系

目的探讨皮质下缺血性血管性痴呆(SIVD)患者认知功能与脑白质弥散张量成像(DTI)的关系。方法采用MMSE、蒙特利尔认知测评量表(Mo CA)及临床痴呆量表(CDR)评价60例SIVD患者(SIVD组)和45名正常对照者(正常对照组)。应用DTI技术测量患者脑白质不同感兴趣区(ROI)各向异性分数(FA)和表观弥散系数(ADC)。SIVD组用常规头颅MRI采用年龄相关白质改变(ARWMC)评分方法对侧脑室周围脑白质高信号严重程度进行评分。结果与SIVD组比较,正常对照组MMSE及Mo CA评分显著增高,CDR评分显著降低(均P0.01)。与正常对照组比较,SIVD组双侧额叶前部、双侧侧脑室前角区及后角区的FA值显著下降,ADC值显著升高(P0.05~0.01)。其余各区FA及ADC值差异无统计学意义。SIVD组ARWMC评分为1分11例(18.3%),2分31例(51.7%),3分18例(30.0%)。正常对照组中5人(11.1%)为1分。Spearman相关性分析显示,SIVD组ARWMC评分与双侧侧脑室前角区及后角区FA值呈负相关(r=-0.912,P0.01),与ADC值呈正相关(r=0.891,P0.01)。双侧额叶前部皮质下白质及海马区FA值与MMSE及Mo CA评分呈正相关(P0.05~0.01)。结论 SIVD患者多个ROI的FA值降低及ADC值的增高程度,可以反映认知功能障碍的程度。