摘要:

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and β/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. β/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.

ISSN:1420-8008    

DOI:10.1159/000106727

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and β/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. β/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.

ISSN:1420-8008    

DOI:10.1159/000315546

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Using computer-enhanced image analysis, the amount of lipofuscin was measured in 500 hippocampal pyramidal neurons (regions CA2 and CA3) with and without neurofibrillary tangles (NFT), in brains of 10 patients with Alzheimer's disease (AD), as well as in 6 age-matched controls. The average content of lipofuscin in those cells from AD brains carrying NFT is only 10% of the total perikaryal area, whereas in the AD neurons free of NFT, and in age matched controls, lipofuscin amounted to 31 and 33% of cellular area, respectively. Measurements of lipofuscin's intrinsic autofluorescence confirmed this material to be three times more abundant in AD neurons without NFT and in controls. We propose that a breakdown in the capacity for making lipofuscin may result in the neuronal inability to store toxic waste. Such a defect could be responsible for the generation of NFT and ultimately may contribute to neuronal demise.

ISSN:1420-8008    

DOI:10.1159/000106728

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Lipofuscin, the age pigment, is of interest in Alzheimer's disease because of its property to accumulate in neurons and because of the hypothesis that Alzheimer's dementia is a kind of premature ageing. The amount of intraneuronal lipofuscin in the inferior olivary nucleus of 20 brains from patients with histologically confirmed Alzheimer's disease according to the CERAD protocol and of 20 controls has been measured microfluorometrically. Patients and controls were matched for age. The amount of lipofuscin in the neurons of the inferior olivary nucleus did not differ significantly between the cases of Alzheimer's disease and the controls. The result is discussed taking the findings of previous authors into account. We conclude that there is no evidence that lipofuscin plays an important role in the pathogenesis of Alzheimer's disease.

ISSN:1420-8008    

DOI:10.1159/000106729

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The frequency of the ε4 allele of the apolipoprotein E (apoE) is increased in familial and sporadic late-onset Alzheimer's disease, but its prevalence in non-Alzheimer dementias in Caucasian populations is unknown. We found that the frequency of the apoE ε4 allele was 0.45 in 93 Alzheimer's disease patients, 0.46 in 23 vascular dementia patients, 0.31 in 13 dementia of the frontal type patients, and 0.18 in 51 elderly controls. The association of apoE ε4 allele is not unique to Alzheimer's disease, and its importance as a risk factor for the disease should be reconsidered.

ISSN:1420-8008    

DOI:10.1159/000106730

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To assess the feasibility of one approach to combined cholinergic/noradrenergic treatment in Alzheimer's disease, ten patients were enrolled in a 2-week placebo-controlled study of oral physostigmine plus clonidine. The Alzheimer's Disease Assessment Scale (ADAS) was used as the primary outcome measure. Neither physostigmine alone, nor the combination of physostigmine plus clonidine, was associated with a statistically significant improvement for the group. Three patients did show an improvement of at least 4 points on the total ADAS score with the drug combination. The implications of these results for treatment strategies are discussed.

ISSN:1420-8008    

DOI:10.1159/000106731

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The density of senile plaques (SP) and neurofibrillary tangles (NFT) was estimated at post-mortem in areas B17 and B18 of the visual cortex in 18 Alzheimer's disease (AD) cases which varied in disease onset and duration. The density of SP in B17 and NFT in B17 and B18 declined significantly with age at death of the patient. The density of SP and NFT was greater in B18 than B17 but only in cases of earlier onset and shorter duration. The pathological differences between B17 and B18 could explain the visual evoked responses (VER) that have been reported in AD. However, the differences were small, and changes in the afferent pathways remain the most likely explanation for the VER in AD.

ISSN:1420-8008    

DOI:10.1159/000106732

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In 40 patients with Alzheimer's disease (AD, <65 years), 56 patients with senile dementia of the Alzheimer type (SDAT, ≥65 years) and 45 patients with vascular dementia (VAD), basal cortisol levels were estimated and the dexamethasone test (DST) was performed. The degree of dementia was assessed according to DSM-III-R and the GBS scale was used for quantitative measures of functional impairment. There were no significant differences in basal cortisol levels. Especially in the VAD group, scores on functional impairment correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in demented patients which can be correlated to the degree of dementia. In VAD, and to a certain extent also in SDAT, there appears to be a disconnection between cortical areas, including the hippocampus and the hypothalamus.

ISSN:1420-8008    

DOI:10.1159/000106733

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The present study compares the sensitivity and specificity of the short and full forms of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) interview in diagnosing dementia. We tested 73 subjects meeting DSM-HIR criteria for dementia and 61 matched controls. The short version was applied 3 months after the full one to guarantee a relative stability of the tested functions. Referred to an independent clinical rating made at the beginning of the study, the levels of sensitivity and specificity were not significantly different in the two forms and fully comparable with those of the original full English version. Moreover, the scores on analogous sections of the two versions were highly correlated in the demented and control groups. These findings support the hypothesis that the short form of the CAMDEX maintains the psychometric properties of the full one, and consequently can be used in diagnostic routines for a variety of clinical and research purposes.

ISSN:1420-8008    

DOI:10.1159/000106734

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The CANTAB battery was administered to a large group (n = 787) of elderly volunteers in the age range from 55 to 80 years. This battery, which is based on tests used to identify the neural substrates of learning and memory in non-human primates, has now been extensively used in the assessment of various forms of dementia and also validated on patients with neurosurgical lesions of the frontal and temporal lobes. The tests employed were pattern and spatial recognition, simultaneous and delayed matching to sample, learning of visuo-spatial paired associates, a matching to sample, reaction time task and a test of spatial working memory. The sample was banded into different IQ bands based on performance on 5 standard tests of intelligence. The MMSE was also administered to exclude cases of possible dementia (n = 16) in the normal sample. In general, performance declined with age and IQ, but these factors did not interact. A factor analysis (with varimax rotation) identified 4 factors with eigenvalues greater than 1, which accounted for over 60% of the variance. Factor 1 was equated with general learning and memory ability and loaded significantly with the Intelligence scores; factor 2 was related to speed of responding and loaded most heavily with Age. Comparisons were also made of performance on CANTAB of those subjects with dementing scores on the MMSE and the lowest 5th percentile of the population sample. The results are discussed in terms of the utility of the CANTAB battery for the assessment of dementia and of the implications for theories of changes in cognitive function during normal aging.

ISSN:1420-8008    

DOI:10.1159/000106735

出版商:S. Karger AG    

年代:1994

数据来源: Karger