摘要:

The cholinergic hypothesis of Alzheimer''s disease (AD) has formed the basis for several approaches at cholinergic replacement therapy, including the administration of anticholinesterases and muscarinic agonists. Although cholinesterase inhibitors such as physostigmine and THA have been shown to improve performance in patients with AD, benefits have been modest. It is anticipated that studies employing cholinesterase inhibitors with an improved pharmacokinetic and safety profile will provide a realistic test of this therapeutic approach. Treatment with non-selective muscarinic agonists has been limited by unacceptable side-effects, and there is a need for subtype selective agents. Currently available functionally selective muscarinic agonists demonstrate low intrinsic efficacy, but it is hoped that the development of truly selective, full agonists will offer a real clinical advantage.

ISSN:1420-8008    

DOI:10.1159/000107015

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Principal component analysis of the Gottfries-Bråne-Steen (GBS) scale was performed. GBS ratings of 221 consecutive patients with suspected or mild to severe dementia formed the basis for the analysis. A four-factor solution and varimax rotation was selected which accounted for 64.5 % of the variance. The components were called Impaired Orientation and Memory, Impaired Ability to Perform Activities of Daily Living, Depression-Anxiety and Impaired Attention and Motivation. This empirically based organization of 22 of the 26 items was used to generate subscales (GBS-F scales). The internal consistency of each of the GBS-F scales was estimated in 2 other samples and was found satisfactory. The GBS-F scales may be used in studies of the course of various dementia disorders and of the efficacy of drug therapy and other interventions aimed at modifying the course of a dementia disorder

ISSN:1420-8008    

DOI:10.1159/000107016

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Ca-independent and Ca-dependent proteolytic activity were significantly higher in erythrocytes from male patients with Alzheimer''s disease compared to control subjects. The level of calpastatin, an endogenous inhibitor of the proteolytic enzyme calpain, was lower in male patients with Alzheimer''s disease. The small changes observed in the female group were not statistically significant. Control male subjects had significantly higher levels of calpastatin compared to female controls. The observed changes in the calpain/calpastatin system of erythrocytes may be caused by a general dysregulation of Ca homeostasis in cells of Alzheimer patients and may lead to calpain-induced pathological changes.

ISSN:1420-8008    

DOI:10.1159/000107017

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

A study was undertaken to investigate the frequency and accuracy of dementia diagnosis in two Swedish nursing homes. The diagnoses of 46 patients were registered from the medical records on the wards. Then the patients were reinvestigated and diagnosed according to DSM-III-R. Ratings were performed using two instruments, the Gottfries-Bråne-Steen scale (GBS scale) and the Mini-Mental State Examination (MMSE). The results of the psychiatric reinvestigation and the ratings showed that 45 of the 46 patients had dementia, while, according to the ward records, dementia was diagnosed in only 9 cases. The discrepancy was striking. The unawareness of dementia in the nursing homes was thus considerable and may have had implications for the planning and quality of the care. Education of the staff with regard to dementia must also be considered. The use of a rating scale for identification of dementia symptoms is suggested

ISSN:1420-8008    

DOI:10.1159/000107018

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The Canadian Study of Health and Aging includes 18 centres, and all provinces are represented. The objectives of the study are: to estimate the prevalence of dementias, especially Alzheimer''s disease; to study risk factors for Alzheimer''s disease; to describe patterns of caring and to measure the burden on those who care for people with dementia; and to create a data base for future research. A representative sample of 10,250 Canadians aged 65 or over are recruited, including 9,000 living at home and 1,250 in institutions. Participants are screened for cognitive impairment. Those who are considered to be cognitively impaired (and an equal number who are not) are invited to undergo a clinical examination including a battery of neuropsychological tests. Proxies for the cases and controls complete a risk factor questionnaire; caregivers complete a separate questionnaire. Results of the pilot study are discussed.

ISSN:1420-8008    

DOI:10.1159/000107019

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The formation of thiobarbituric-acid-reactive substances (TBARS) indicative of oxygen-induced lipid peroxidation in vitro was assayed in the frontal cortex, hippocampus, putamen, basal nucleus of Meynert and substantia nigra from controls and patients with Alzheimer''s disease. A significant increase of oxygen-stimulated formation of TBARS in vitro was found in the frontal cortex and substantia nigra of Alzheimer''s-type brains, while there was only a trend to an increase in the basal nucleus of Meynert. In addition, induction of lipid peroxidation in vitro by incubation with a Fenton reagent did not result in significant differences between control and pathological brain areas. Levels of total iron in the brains from patients with Alzheimer''s disease and controls did not differ significantly with respect to the same brain region investigated. Further analysis of frontal cortex, substantia nigra and basal nucleus of Meynert using differential scanning calorimetry revealed significantly lower thermostability of these areas in Alzheimer''s disease. Our data suggest that, within distinct brain regions, Alzheimer brains differ from normal brains with respect to their susceptibility to peroxidation in vitro and to their resistance to thermic stress. These results implicate changes in cell membrane constituents and cytoarchitecture.

ISSN:1420-8008    

DOI:10.1159/000107020

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We report a case of dementia in which cortical degeneration with widespread presence of swollen chromatolytic neurons was the dominant pathologic feature. The previously healthy woman began to notice psychiatric symptoms at the age of 52 years. The symptoms and neurological signs progressed inexorably over the next 4 years. By the time of her death at 56 years of age, she was hopelessly disabled and lay in a mute, rigid, immobile, and seemingly insensate condition. Ultimately, quadriplegia in flexion and profound dysfunction of the extrapyramidal system, the ''akinetic-rigid syndrome'' were noted. In this patient the relentlessly progressive course, without remissions, suggests a degenerative process. Pathological examination showed frontoparietal atrophy with nerve cell loss and the presence of swollen chromatolytic cells, but there were no Pick bodies. There was nerve cell loss and gliosis in the pigmented portion of substantia nigra. Despite some pathological similarities to Pick''s disease we suggest that the distribution of nerve cell loss and the absence of Pick bodies and white matter lesions are unique to this case. Comparison of swollen chromatolytic neurons with other cerebral degenerative disorders indicates a similarity with corticonigral degeneration. This case could be included as a type of primary degenerative dementia.

ISSN:1420-8008    

DOI:10.1159/000107021

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This work describes the distribution of the central benzodiazepine-binding sites (BZD-BS) in several structures recently described as involved in memory processes. The study was performed on 4 postmortem human brains by in vitro quantitative autoradiography using 3H-flunitrazepam as a ligand. Very high densities of BZD-BS (1,500–2,000 fmol/mg protein) were observed in the anterior and posterior cingulate cortex, in the indusium griseum and in the accessory basal nucleus of the amygdala, and moderate concentrations (500–700 fmol/mg) in the magnocellular region of the mediodorsal thalamic nucleus. In the classical cerebral memory circuits, high densities of BZD-BS (1,000 to 1,500) were also found, except in the septum where the density of BZD-BS (400 to 600) was not significantly different from that in control structures not involved in memory. No evidence for lateralization of the sites was obser

ISSN:1420-8008    

DOI:10.1159/000107022

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Benzodiazepine and muscarinic receptors in the neocortex were studied using homogenate binding techniques and in vitro autoradiography (ARG). Tritiated flunitrazepam was used to bind to the benzodiazepine portion of the γ-aminobutyric acid receptor. Tritiated quinuclidnyl benzilate was used to locate the muscarinic receptor. Tissue samples from four areas of neocortex from cases of Parkinson''s disease, Alzheimer''s disease and age-matched controls were used for homogenate binding experiments to estimate binding parameters. Tissue for ARG provided more detailed anatomical localization of the relevant receptors. Homogenate binding studies showed that the receptor density, as measured by maximum binding capacity for tritiated flunitrazepam, was significantly reduced in the frontal cortex in Parkinson''s disease. In Alzheimer''s disease there was reduced binding of flunitrazepam in all portions of the neocortex studied, reaching statistical significance in the frontal and temporal cortex. The dissociation constant, indicating receptor affinity for flunitrazepam, was unaltered in all areas studied. ARG demonstrated that the distribution of benzodiazepine receptor loss within different cortical layers was distinct in Parkinson''s and Alzheimer''s disease. In control brains, the greatest density of benzodiazepine receptors was seen in regions corresponding to layers II and III. This peak was greatly reduced in the frontal cortex of Parkinson''s disease, while in Alzheimer''s disease the loss was more uniform. There was no significant alteration in the binding parameters of the muscarinic cholinergic receptors in either of these disease states

ISSN:1420-8008    

DOI:10.1159/000107023

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This experiment examined the retention of a passive avoidance response in 1-, 2-, 10- and 18-month-old C57BL/6 mice. Retention performance was assessed after training-test intervals of 24, 48 and 72 h. Adult (2 months) animals always reached the highest performance. At each interval the decline in retention performance (i.e. the rate of forgetting) varied according to the age group. With increasing testing intervals, the retention times of young, mature and old animals tended to become similar.

ISSN:1420-8008    

DOI:10.1159/000107024

出版商:S. Karger AG    

年代:1992

数据来源: Karger