摘要:

We have analyzed the tendency of amyloid load, neuritic plaques and neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in Clusters in 49 consecutive cases of Alzheimers disease (AD). This clustering tendency of the pathology was analysed in relation to severity of clinical disease assessed within 6 months before death, duration and age at onset of disease and at death. Amyloid plaques showed only a slight tendency to cluster together while neuritic plaques and, even more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly strong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clustering tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic plaques showed similar but less pronounced and robust correlations between clustering and cognitive status. In the hippocampus NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that clustering characterises neuritic pathology but not diffuse amyloid deposits and significantly affects cognition. The discrepancies between the group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a signiflcant effect on the cognitive status of AD patients.

ISSN:1420-8008    

DOI:10.1159/000106866

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The most important new development during recent years in the field of degenerative dementia concerns synaptic pathology. So far it has been investigated in some regions and some cortical laminae in Alzheimer''s disease (AD). The present communication is a more comprehensive study of all laminae in four different regions, the prefrontal, parietal, inferior temporal and posterior cingulate cortex. Against the background of normal aging, AD was compared with another degenerative disorder, frontal lobe degeneration of non-Alzheimer type (FLD). The synapse density was measured using synaptophysin as a marker. Astrocytes were also counted in the molecular layer. In normals, the cortex showed successively lower synaptic density from layer I to layer VI and relatively lowest density in the prefrontal cortex and a general decline with increasing age. A 46-49% decrease in synaptic density was found in all laminae in all regions of AD brains, a finding different from that in FLD. The number of astrocytes increased significantly in the prefrontal cortex both in AD and FLD but parietally only in AD. These results contribute to the understanding of normal synaptic organization of cortex, demonstrate the laminar and regional distribution of synaptic loss in AD and underscore the difference between AD and FLD. The gliosis appears to be secondary to the neurodegenerative changes. Synaptic loss is likely to be a common pathogenetic feature of neurodegenerative disorders and a likely cause of clinical symptoms and regional metabolic decrements in dementia.

ISSN:1420-8008    

DOI:10.1159/000106867

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Individual differences in the development of neurofibrillary changes were examined in eight cortical regions in the brains of 43 subjects with Down syndrome (DS; age range, 15-69 years) using sections stained with monoclonal antibodies (mAb) tau-1 and 3-39. Neurofibrillary pathology was found in 4 cases below 36 years of age and in all 20 cases above that age. In the 24 positive cases, numerical density of pretangles stained with tau-1 and 3-39, respectively, was 6.1/mm2 and 0/mm2; early tangles, 5.0/mm2 and 5.3/mm2; mature tangles, 4.0/mm2 and 5.0/mm2 (p < 0.01); and end-stage tangles, 0.04/mm2 and 2.5/mm2 (p < 0.001). Numerical density of pretangles stained with mAb tau-1 and tangles and plaques stained with mAb 3-39 correlates weakly with age (r = 0.43; p < 0.02), and together with the wide range of numerical densities suggested heterogeneity of the population examined. Cluster analysis based on two variables – i.e., numerical density of pretangles stained with mAb tau-1 and neurofibrillary tangles (NFTs) and plaques stained with mAb 3-39, distinguished three groups of subjects with severe, moderate and weak changes. The severely affected group of 5 subjects (21%) had an average 54.6/mm2 of neurons and 13.9/mm2 plaques with neurofibrillary changes, whereas the moderately affected group (6 subjects; 25%) showed a significantly lower numerical density of neurons and plaques with neurofibrillary changes (25.7/mm2 and 8.1/mm2, respectively) as compared with the most affected group. Most of the subjects (13; 54%) belong to the third group with only 2.2/mm2 of neurons and 1.4/mm2 plaques with neurofibrillary pathology. Comparison of these three groups of Down syndrome subjects representing high, moderate, and low susceptibility to neurofibrillary changes with the general population suggests that the risk of Alzheimer disease is similar but the onset of pathological changes is earlier in D

ISSN:1420-8008    

DOI:10.1159/000106868

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The present study is a retrospective study of remoxipride therapy. A total of 103 patients, 65 years or older, with a DSM-III-R diagnosis of dementia or delirium, were included. They had all been treated with remoxipride because of psychotic symptoms or behavioural disturbances. The dose range of remoxipride was 50-300 mg, the median dose being 75 mg. The clinical effect was rated as good in two thirds of the patients, and side-effects were noted in one fourth. When psychomotor hyperactivity was the dominating problem, a good effect was rated in 81 % of the patients. Side-effects were few and mild, the most common being tiredness; only 5 patients showed extrapyramidal symptoms.

ISSN:1420-8008    

DOI:10.1159/000106869

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A physiopathological role for acetylcholine (ACh) was hypothesized during ageing and related neurodegenerative diseases, e.g. dementia. This research was aimed to study acetylcholinesterase (AChE) activity during development and ageing of the frontal cerebral cortex of 4-, 8-, 12-, 16-, 20- and 24-month-old rats. This study was performed on synaptic plasma membranes, the specific subcellular compartment where the enzyme is located in vivo both in control animals and after in vivo acute treatment with L-acetylcarnitine. Maximum AChE activity was unaffected by age, and L-acetylcarnitine treatment increased enzyme activity in synaptic plasma membranes of 8-month-old rats. A comprehensive analysis of these results suggests: (a) the observed alterations in protein can substantially affect neurochemical data if results are presented as specific activities per unit protein; (b) energy metabolism plays the major role in the disturbed ACh metabolism during ageing and (c) the understanding of the mode of action of L-acetylcarnitine in treatment of dementia.

ISSN:1420-8008    

DOI:10.1159/000106870

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We report the behavioural abnormalities, neuroimaging, and neuropsychological results of a 62-year-old patient, IP, who shows a clinical profile that fulfils all characteristics of dementia of frontal lobe type. The patient has been followed up over 5 years with psychometric testing. Comparing her cognitive profiles across examinations, her performance was substantially unchanged apart from behavioural disturbances and performance on frontal tasks which showed a progressive worsening. MRJ finding evidenced marked ventricular enlargement, prevalent frontal atrophy and hypertrophy of the genus of corpus callosum. SPECT investigation showed a considerable reduction of cerebral blood flow in the mesial parts of the frontal lobes, in the lateral surface of the right fronto-parietal lobe, and hypo-perfusion in the right thalamic area. The results are discussed with reference to the features (clinical and neuropsychological) which distinguish different profiles of dementia.

ISSN:1420-8008    

DOI:10.1159/000106871

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The cascade of reactions caused by ischemia in brain tissue is complex and not completely understood, but intensive investigation has led to convincing hypotheses. A disturbed calcium homeostasis and oxygen radicals seem to play a major role in postischemic neuronal damage. In accordance to these hypotheses drugs with different mechanisms of action have been developed. The aim of this paper is to give an overview over pathobiochemical mechanisms in cerebral ischemia and possibilities of pharmacological intervention.

ISSN:1420-8008    

DOI:10.1159/000106872

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

An increased apolipoprotein E (ApoE) type ε4 allele frequency is associated with both sporadic and familial late-onset Alzheimer''s disease (AD). The age of onset of disease in patients homozygous for the ε4 allele appears to be decreased by approximately 15 years compared with E2/3 individuals. In order to assess the influence of this allele on both dementia and cognitive decline in the elderly we have determined the ApoE genotype of 150 individuals over the age of 75 years who have taken part in a longitudinal study. Homozygosity for the ε4 allele was rare. Of the 2 homozygotes, 1 was severely demented but the other did not receive a clinical diagnosis of dementia. The latter individual did demonstrate marked cognitive decline over a 28-month period. There was a consistent association between the presence of an ε4 allele and both the clinical diagnosis of dementia and cognitive decline. These findings confirm a genetic heterogeneity in late-onset sporadic AD and prompt caution in the use of ApoE genotype to predict an elderly individual''s susceptibility to either dementia or cognitive decline.

ISSN:1420-8008    

DOI:10.1159/000106873

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000106874

出版商:S. Karger AG    

年代:1996

数据来源: Karger