Serum auto-antibodies in Alzheimer''s disease

The prevalence and clinical significance of non-CNS auto-antibodies in the serum of patients with probable and possible Alzheimer's disease (AD) was determined. Serum was obtained from 88 patients and 55 normal controls. Serum from each subject was tested for the presence of seven different auto-antibodies. Auto-antibodies were detected in 44% of the subjects with probable AD, 70% with possible AD with cerebrovascular disease (CVD), 45% with possible AD and other disease and 42% of normal controls. Although a subpopulation of AD patients with CVD showed a trend to an increased predisposition to develop autoimmune disease, these results do not support the relationship of AD and serum auto-antibodies or autoimmune disease.     

Alzheimer''s disease: neuropathological correlates of cognitive and motor disorders

Correlations between clinical symptoms and changes in brain neuropathology were investigated in 34 patients with Alzheimer's disease, who were compared with 17 non-demented, age-matched controls. The patients were originally found in a community survey of dementia and were followed up prospectively until death. A highly significant correlation emerged between the severity of dementia and the numbers of plaques and tangles in the material as a whole, but no essential difference was found between severely and less severely demented patients. Low brain weight correlated highly with many clinical symptoms and signs and the severity of dementia. A multiple regression model consisting of plaques and tangles in amygdala, gyrus frontalis medius, gyrus angularis, and gyrus temporalis medius, plaques of gyrus rectus, tangles of the hippocampus, gyrus precentralis and gyrus cinguli together with brain weight, emerged to link dementia to neuropathological changes at the level of maximum significance. Dyskinetic movements were associated with damage of several brain areas, implying a multiple etiology.     

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.     

Presenilin immunoreactivity in Alzheimer''s disease

The role of presenilin (PS) mutations in familial Alzheimer's disease (AD) may be as a toxic gain of function, but in sporadic disease their contribution is more difficult to understand. In this study, we investigated PS proteins in sporadic AD by comparing the immunocytochemical profiles in sporadic AD with control brains using a quantitative immunocytochemical approach to both the N- and C-terminals of PS1 and PS2. Ten patients with pathologically proven AD (using modified Consortium to Establish a Registry for Alzheimer's Disease [CERAD] criteria) and 10 controls were age- and sex-matched. The immunocytochemical primary antibodies were affinity-purified goat polyclonal antibodies and the secondary antibodies were biotinylated donkey anti-goat to the N- and C-terminal of both PS1 and PS2. The number of PS-containing neurones was quantified manually and without the knowledge of the diagnosis. We found no significant differences in the number of PS1- and PS2-containing neurones in three anatomical regions for both N- and C-terminals between AD and controls. Our findings argue in favour of functional changes in PS molecules contributing to the pathogenesis of AD and are consistent with the hypothesis of dysfunction of the entire gamma-secretase complex, of which PS proteins are a constituent.     

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.     

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.     

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。     

Recent advances in the neuropsychology of Alzheimer''s disease

1. Memory, language, and visuospatial impairments are prominent neuropsychological deficits in Alzheirner's disease.

2. The neuropsychological characteristics of Alzheimer's disease are unigue, and contrast with those of other brain diseases.

3. Neuropsychological study of patients with Alzheimer's disease may he useful in discovering the neuronal basis of cognitive processes, in differential diagnosis of dementia, and in evaluating treatment.     

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.     

Alzheimer''s disease and senile dementia of Alzheimer type

Clinical and neuropsychological findings, EEG, and several blood and CSF parameters were investigated in 36 patients with Alzheimer's disease (AD) and 35 patients with senile dementia of Alzheimer type (SDAT). There were more women among senile patients and more familial cases among presenile patients. The average duration of the symptoms was longer in presenile patients (6.1 years) than in senile patients (3.9 years). This could be due to the lower resistance to the disease process in the senile group.
Extrapyramidal signs, especially rigidity, were found in over 60 % of all patients and in practically all patients with advanced dementia. Tremor was found in three patients only. Four presenile (11 %) and two senile (6 %) patients had epileptic seizures. All patients had abnormal EEG recordings, mainly in form of diffuse slowing. A positive correlation was found between the EEG abnormality and the severity of dementia in AD but not in SDAT. However, the difference between the correlation coefficients in AD and SDAT was insignificant. Between EEG and the duration of the disease there was no correlation. EEG was not more abnormal in very severe dementia than in severe dementia. Other findings were similar in AD and SDAT.
It is concluded that it is artificial to separate AD and SDAT at the age of 65 and that they clinically compose a single entity. This entity could well be called Alzheimer's disease.     

Erythrocyte glutathione peroxidase and superoxide dismutase in Alzheimer''s disease and other dementias

Activities of 2 enzymes protecting from free radical damage, erythrocyte glutathione peroxidase and superoxide dismutase, were measured in 4 patients with Alzheimer's disease, in 4 with multi-infarct dementia, in 1 with Huntington's disease and in 1 with Hakola-Nasu disease. In none of these dementing diseases the activities were diminished compared to controls.     

阿尔茨海默病实验性研究进展

阿尔茨海默病（Alzheiwer's Disease,AD）是最常见的与年龄相关的痴呆性疾病。随着人类平均寿命的增长，AD病人不断增多，医疗消费逐渐增长。所以基础与临床都十分重视AD的研究。AD属进行神经变性疾病。临床特征为认知障碍。其病理学改变是临床诊断的最可靠根据，包括细胞外淀粉样变性斑块和细胞内神经元缠结形成。以病因学角度，AD 属基因异原性遗传性疾病。最近10年的研究显示APP，PS1，PS2以及ApoE基因与AD具有肯定的联系。目前认为前三为AD的致病性基因，而ApoE则是危险性基因。本报告了近10年的AD基础研究进展，着重于淀粉条变致源学说，危险因素ApoE以及其他基因学及危险因素的研究。     

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.     

Platelet membrane fluidity in Alzheimer''s disease and multi-infarct dementia: a spin label study

The membrane fluidity of platelets isolated from 15 patients with probable Alzheimer's disease (AD), 11 patients with probable multi-infarct dementia (MID), and 7 neurologically healthy controls was studied by electron spin resonance (ESR) spectroscopy employing spin label techniques. Spin label I(12,3) probed the shallow site (hydrophilic region) and spin label I(5, 10) the deeper site (hydrophobic region) of the platelet membrane. With both probes, a significant increase in membrane fluidity was observed in patients with AD and MID, as compared to age-matched controls. However, there were no significant differences in fluidity between AD and MID patients. Our results suggest an increased platelet membrane fluidity in dementias, but the change seems not to be specific 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.     

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.     

Mamillary bodies in Alzheimer''s disease

The number of senile (neuritic) plaques (SP) and neurofibrillary tangles (NFT) in mamillary bodies (MB) and in the dorsomedial nucleus of the thalamus (DMNT) were assessed in 25 cases of definite Alzheimer's disease. In 20 cases with AD without other CNS disease the MB and DMNT showed SP and/or NFT in 19 (95%). No correlation was found between the number of SP and NFT and the duration or age of onset of the disease. In patients with AD plus another CNS disease, there were fewer SP and NFT regardless of duration and age at onset of the disease. AD is a diffuse disorder with cortical and subcortical changes. The involvement of MB and DMNT suggests that subcortical structures are also implicated in the memory disorder of AD. The association of AD with other diseases that can themselves cause dementia requires further studies, especially regarding the pattern of topographic distribution of the degenerative changes.     

Hippocampal membrane alteration in Alzheimer''s disease

The biophysical properties of hippocampal membrane preparations from patients with Alzheimer's disease were examined by fluorescence spectroscopy using the membrane lipid probe 1,6-diphenyl-1,3,5-hexatriene (DPH) and its cationic derivative 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). Results of these experiments suggest that Alzheimer's disease is associated with a biophysical alteration in superficial regions of brain cell membranes, as reflected by the mobility of TMA-DPH. In contrast, no change in the mobility of DPH, which preferentially localizes to the hydrocarbon core, was observed. Although a trend was observed for TMA-DPH mobility to parallel histopathologic severity in hippocampal specimens, the biophysical changes did not appear to reflect a loss of neuronal membranes relative to glial membranes or the presence of senile plaques or neurofibrillary tangles.     

The cortex of the primary auditory area in Alzheimer''s disease

The cortex of the superior temporal gyrus has been examined in two brains with Alzheimer's disease. Numerous neurofibrillary tangles and neuritic plaques that are characteristic of the disease, were present in area 38 in the anterior part of the gyrus and in area 22 more posteriorly but the primary auditory cortex, area 41, was virtually unaffected by these pathological changes. This relatively minor involvement of the primary auditory cortex, like that of the primary somatic and visual areas, again emphasises the uniqueness of the olfactory system in being severely degenerate. The findings are considered to support the suggestion that the distribution of the pathological changes in Alzheimer's disease has an anatomical basis due to spread of the disease process along certain well-defined sets of cortical fibre connections.     

Glioblastoma multiforme of the hippocampus in advanced Alzheimer''s disease

An 87-year-old woman suffered from Alzheimer's disease diagnosed 6 years prior to her death. Autopsy showed in addition to far-advanced Alzheimer's disease, a large, partially necrotic glioblastoma occupying her right hippocampus. Occurrence of a glial neoplasm in Alzheimer's disease could well be coincidental, since both entities are fairly common in elderly individuals; it is however, uncommon for gliomas to centre on the hippocampus itself. For these reasons it is possible (although cannot be proven from a single case), that florid reactive gliosis commonly associated with Alzheimer's disease, may have played a role in eventually initiating neoplastic proliferation of astrocytes in this patient.