Sulfatide as a biochemical marker in cerebrospinal fluid of patients with vascular dementia

The myelin-associated glycosphingolipid sulfatide in cerebrospinal fluid (CSF) was investigated in 20 patients with vascular dementia (VAD), 43 with Alzheimer's disease (AD) and 20 age-matched controls. The sulfatide concentration in the VAD group (307 +/- 118 nmol/l) was significantly (p less than 0.0001) higher than that in controls (145 +/- 86 nmol/l) and the AD group (178 +/- 79 nmol/l). Among the VAD patients, 8/20 had a significantly increased concentration of sulfatide (greater than mean + 2 S.D.), as compared with controls, while only 2/43 of the AD patients had a sulfatide concentration above this level. It is suggested that the elevated concentration of sulfatide in CSF from VAD patients reflects demyelination. Furthermore, sulfatide determinations, when combined with clinical findings, may be of diagnostic value, for discriminating between VAD and AD.     

Intrathecal synthesis of immunoglobulin G in vascular dementia

Serum and CSF from 53 vascular dementia (VD) patients and 50 controls were analysed to investigate the possibility of an intrathecal synthesis of IgG, defined as an elevated IgG index (greater than or equal to 7) and/or presence of oligoclonal IgG in cerebrospinal fluid (CSF), but not in serum. Five (9%) patients and no controls exhibited an intrathecal synthesis of IgG. The IgG index increased with the degree of dementia (p less than 0.05). It was positively related to presence/absence of hypertension (p less than 0.05) and correlated positively with diastolic blood pressure (p less than 0.05). The findings suggest that immunological factors might be involved in the pathogenesis of VD.     

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.     

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.     

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.     

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。     

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.     

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.     

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     

Oligoclonal bands in cerebrospinal fluid: a comparative study of isoelectric focusing, agarose gel electrophoresis and IgG index

OBJECTIVE: To compare the sensitivity and specificity of isoelectric focusing (IEF) with immunofixation, agarose gel electrophoresis (AGE) and the IgG index in detecting intrathecally synthesized IgG in multiple sclerosis (MS) and in other nervous system disorders. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and serum from 147 patients with various nervous system diseases, 20 of whom had MS, were compared with IEF, AGE and the IgG index. RESULTS: CSF-restricted oligoclonal bands (OCB) were found in 20 of 20 patients with MS using IEF and in 9 of 20 using AGE. OCB were found in 12 patients with other nervous system disorders (OND) using IEF and 4 using AGE. The mean IgG index was 0.50 in OND and 0.96 in MS (P< 0.0001). Of 20 MS patients, 9 had an IgG index above the defined cut-off value of 0.72. CONCLUSIONS: IEF is about twice as sensitive as AGE in detecting OCB in MS. IEF is also far superior to the IgG index in determining intrathecal IgG synthesis.     

Oligoclonal immunoglobulin G in cerebrospinal fluid of myasthenia gravis patients

Immunoglobulin G (IgG) band patterns were investigated in cerebrospinal fluid (CSF) from 19 patients with myasthenia gravis (MG) in a search for abnormalities indicating central nervous system (CNS) involvement in this disorder. Using the isoelectric focusing (IEF) technique and antiserum immunoblotting against IgG, we found no evidence of the presence of oligoclonal IgG in CSF from most of MG patients. In 2 cases, the positive findings of oligoclonal IgG in CSF may have reflected a manifestation of an associated disease, which has already been associated with immune abnormalities within the CNS. Further investigations with more sophisticated techniques are required to give additional insight into humoral immune events within the CNS in MG patients.     

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.     

The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia

Abstract.Background: Recent guidelines from the United States and Europe on the diagnosis and management of dementia include advice that younger patients with dementia should undergo CSF examination, which frequently includes analysis for oligoclonal bands (OCB). The presence of CNS specific OCB has traditionally been considered suggestive of an inflammatory aetiology, although the interpretation of such a finding in the presence of a normal CSF white cell count and protein is more difficult.Methods: We reviewed retrospectively the prevalence of OCB, determined using agarose isoelectric focusing, in a series of 131 well characterised patients with a final diagnosis of a degenerative dementia who had undergone CSF examination.Results: The mean age of the patients was 60.0 (SD 8.4) years. Seventy (53%) patients had Alzheimers disease (AD), forty seven (36 %) had frontotemporal lobar degeneration (FTLD), seven (5%) had Dementia with Lewy bodies and the remaining seven (5%) patients had other rarer neurodegenerative dementias. Neuropathological examination had been performed in fifteen (11%) patients. CNS specific OCB were present in nine (7%) patients in this cohort, all of whom had normal CSF white cell counts: four AD patients (a prevalence of 6%), four FTLD patients (a prevalence of 9%), and one patient with Creutzfeldt-Jakob disease (a prevalence of 25%). Investigation of these patients, including two with neuropathologically verified AD and one with post-mortem confirmed CJD, did not reveal an alternative aetiology for their dementia.Conclusion: A central immune response can occur in primary neurodegenerative dementias, albeit uncommonly.     

Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia

Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.     

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.     

Dopamine-β-hydroxylase and acetylcholinesterase activities of cerebrospinal fluid in Alzheimer''s disease

Recent neurochemical studies have indicated that in Alzheimer's disease there is disturbance of the cholinergic metabolism of the brain. Defects in other transmitter systems have also been suggested. As a marker of noradrenergic metabolism of the central nervous system, we measured dopamine-beta-hydroxylase (EC. 1.14.17.1) activity in cerebrospinal fluid (CSF) from 60 Alzheimer patients and 20 controls of the same age and sex. Dopamine-beta-hydroxylase activities of the CSF from Alzheimer patients did not differ significantly from those for the controls. The dopamine-beta-hydroxylase activities were not correlated with severity of dementia. As reported previously, the activity of a cholinergic marker, acetylcholinesterase (EC 3.1.1.7), was reduced in the CSF of Alzheimer patients. Interestingly, dopamine-beta-hydroxylase activities were correlated with acetylcholinesterase activities both in Alzheimer patients and control group.     

Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy bodies in a Japanese population

We studied the prevalence of dementing disorders in a rural town of Japan (Amino-cho), using a door-to-door two-phase design. Of the 170 persons screened as having cognitive impairment, 142 cases were diagnosed as having dementia. The prevalence (cases/100 aged 65 years older) was 3.8 for all types of dementia, 2.1 for Alzheimer's disease (AD), 1.0 for vascular dementia (VD) and 0.7 for other types of dementia. Among other types of dementia, there were four male patients with dementia with Lewy bodies (prevalence: 0.1), but no patients with frontotemporal lobar degeneration. The overall prevalence was higher in women for AD, while that of VD was the same in both sexes. With results similar to many previous studies in Western countries and some recent surveys in Japan, the present sudy clearly showed that AD is more prevalent than VD.     

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.     

阿尔茨海默病与血管性痴呆患者临床特征和影像学比较

目的 探讨阿尔茨海默病(AD)和血管性痴呆(VaD)患者的临床特征和影像学改变,以期寻找鉴别诊断的方法. 方法 收集武警广东医院老年病科自2006年8月至2011年6月收治的162例和同期本地区痴呆症状调查发现的42例痴呆患者的临床资料,采用简易精神状况检查(MMSE)量表进行筛选,其中AD患者114例、VaD患者90例,分析并比较AD、VaD患者的认知能力、行为症状和影像学资料. 结果 与VaD患者比较,AD患者女性较多,文化程度普遍较高,病程更长,差异有统计学意义(P＜0.05);VaD患者注意和计算分项评分低于AD患者,AD患者短程记忆、语言复述和阅读理解分项评分低于VaD患者,差异有统计学意义(P＜0.05); AD患者重复收敛行为的发生高于VaD患者,差异有统计学意义(P＜0.05);AD患者海马萎缩的比例高于VaD患者,VaD患者脑区域发生血管病变的发生率明显高于AD患者,差异均有统计学意义(P＜0.05). 结论 AD和VaD患者具有不同的临床特征和影像学改变,是由各自的病变本质、病变部位和病理机制所共同导致的.