摘要:

The regional brain distribution and selective binding of the cholinergic muscarinic receptor agonist CI-979 labelled with 11C was studied in rhesus monkeys by means of positron emission tomography. The selective binding was measured as displacement of [11C]CI-979-derived radioactivity following constant-rate infusion of CI-979 at doses of 0.5–10 µg/kg/h. An extensive and rapid distribution of [11C]CI-979 was observed to the basal ganglia and temporal occipital cortices, i.e., regions of the brain with a high density of muscarinic receptors. The radioactivity was dose-dependently decreased in cortical regions following infusions of unlabelled CI-979 (0.5–10 µg/kg/h), indicating selective receptor binding of [11C]CI-979 in these brain regions. The binding of [11C]CI-979 was unaltered or even higher in the striatum following unlabelled CI-979 infusion. The high densities of autoreceptors in the striatum may explain the inhibitory feedback mechanism on endogenous acetylcholine induced by the muscarinic receptor agonist. Since muscarinic receptor agonists release acetylcholine, the higher releasable pool of acetylcholine in the striatum will induce feedback inhibition of acetylcholine release and less competition between acetylcholine and CI-979 at the muscarinic receptors. This may explain the differences between cortex and striatum in [11C]CI-979 binding. The cerebral blood flow was not changed by the infusion of unlabelled CI-979, supporting the assumption that effects of CI-979 in brain may be due to the interaction with brain muscarinic receptors. Despite a relative rapid clearance of [11C]CI-979 radioactivity from binding in the brain characteristic of a receptor agonist, the radioligand might be useful in positron emission tomography studies to reveal changes in cholinergic receptors and functional activity in Alzheimer patients treated with muscarinic ago

ISSN:1420-8008    

DOI:10.1159/000106642

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Complement-activated oligodendroglia (CAOs) are thought to represent complement bearing damaged oligodendroglia for opsonization. The interrelationship between CAOs and amyloid deposits was examined by immunohistochemistry in the parietal lobe of patients with Parkinson''s disease, diffuse Lewy body disease, and pallido-nigro-luysial atrophy. In all brains, the anti-C4d antibody stained numerous CAOs. Anti-β-amyloid protein (anti-Aβ) antibody revealed moderate numbers of senile plaques, including some of the classical type. In both the grey and the white matter amyloid deposits were frequently associated with the myelinated axons of CAOs. CAOs were occasionally associated with phagocytosing microglial cells. Immunoelectron microscopy also showed a close relationship between phagocytosing microglia and Aβ deposition. On some occasions, Aβ deposits were seen in C4d-positive oligodendroglial cell bodies. These results indicate that damaged myelinated axons, which contain accumulated amyloid precursor protein, are the source of Aβ, and that CAOs may be initial targets for Aβ deposits forming the classical senile pl

ISSN:1420-8008    

DOI:10.1159/000106643

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Introduction: The Alzheimer Disease Assessment Scale (ADAS) is a scale specifically structured for the assessment of the cognitive decline and behavioral disorder seen in Alzheimer disease (AD) patients. Aim of the Study: The validation of ADAS in the Greek population. Material: One hundred and thirty-one subjects took part in the current study. Fifty of them were nondemented subjects (35 normal subjects and 15 suffering from age-associated memory impairment) and 81 demented patients (68 AD patients and 13 vascular dementia, VD, patients). Method: Diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. Hachinski Ischemia Scale was used to help to differentiate between AD and VD patients. Geriatric Depression Scale was used to quantify depressive symptomatology. MMSE and CAM-COG were used to assess the cognitive functioning of all subjects and FRSSD for the assessment of daily functioning. All subjects underwent a complete laboratory and biochemical testing, according to the protocol proposed in CAMDEX. All demented patients underwent brain CT. Results: ADAS-Cog discriminates perfectly AD patients and nondemented subjects at the score level of 13/14 and/or 14/15. Principal components analysis, using only AD patients, revealed 4 factors: cognitive, psychotic, depressive, and ''severe apraxia'' factors. Conclusion: ADAS is suitable for use in the discrimination between AD patients and nondemented subjects. It is also suitable for a more comprehensive assessment of the clinical symptomatology of AD patients, and for the evaluation of new therapeutic methods for AD, as well.

ISSN:1420-8008    

DOI:10.1159/000106644

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Performances of 12 patients with Alzheimer''s disease (AD), 15 healthy elderly subjects and 20 young healthy volunteers were compared on two episodic memory tests. The first, a learning test of semantically related words, enabled an assessment of the effect of semantic relationships on word learning by controlling the encoding and retrieval processes. The second, a dual coding test, is about the assessment of automatic processes operating during drawings encoding. The results obtained demonstrated quantitative and qualitative differences between the populations. Manifestations of episodic memory deficit in AD patients were shown not only by lower performance scores than in elderly controls, but also by the lack of any effect of semantic cues and the production of a large number of extra-list intrusions. Automatic processes underlying dual coding appear to be spared in AD, although more time is needed to process information than in young or elderly subjects. These findings confirm former data and emphasize the preservation of certain memory processes (dual coding) in AD which could be used in future therapeutic approaches.

ISSN:1420-8008    

DOI:10.1159/000106645

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Alzheimer''s disease (AD) represents a heterogeneous disorder, and several factors have been associated with its development. The presence of the apolipoprotein E type (APOE) ε4 allele has been proposed as a risk factor for AD, but how it influences the development of the characteristic hallmarks of the disease remains unknown. In the present study, the neuropathological changes and levels of both core PHF-tau and normal tau protein in 4 neocortical areas, cerebellum and medial temporal cortex were determined in 18 AD cases. The extent of these changes was compared between 10 cases possessing an εεallele and 8 cases without. These two groups were indistinguishable in terms of neurofibrillary pathology, whereas cases with an ε4 allele had more diffuse plaques, particularly in the temporal neocortex. Biochemically, there was no difference in the levels of PHF-tau protein between the two groups. These data indicate that APOE ε4 allele may influence deposition of diffuse amyloid, but altered tau protein processing, which underlies the development of the neurofibrillary pathology in AD, is not influenced by this allele.

ISSN:1420-8008    

DOI:10.1159/000106646

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In order to study the properties of β-amyloid in vivo, we generated a total of 28 transgenic founder mice that harbored the gene for the 17-amino acid signal sequence and the 99-amino acid carboxy-terminal fragment (CTF) of the human amyloid-β protein precursor (βAPP) linked to the cytomegalovirus enhancer and chicken β-actin promoter. Two of these founders, termed 0304 and 0809, exhibited decreased behavioral activity with gliosis and neurodegeneration in the hippocampus at 2.5 and 9 months of age. Both mice had also decreased levels of synaptophysin, a presynaptic marker, but no evidence for β-amyloid deposition in their brains. Neurodegeneration in the hippocampus was transmitted to the offspring of mouse 0304, although the frequency was low (5 of 44 mice examined) and the time of onset of the disorder was rather later than that in the founder mouse. This is probably due to reduced levels of the transgene-derived products in the offspring of mouse 0304. The 0809 line failed to produce its offspring. The other remaining transgenic founders appeared normal and had lesser amounts of the CTF mRNA and protein in their brains than did 0304 and 0809 founders, though some mice died in earlier stages or exhibited hydrocephalus. These findings suggest that overexpression of the CTF of human βAPP has the potential to elicit neurodegeneration in vivo without appreciable production of β-amyloid f

ISSN:1420-8008    

DOI:10.1159/000106647

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Spontaneous natural killer (NK) cell activity and NK-induced cytotoxicity after interferon-γ (IFN-γ) were measured in healthy elderly subjects and in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). Normal basal and IFN-γ-stimulated NK cytotoxicity were found in healthy old subjects and in patients with MID. On the contrary higher NK cytotoxicity after IFN-γ (650 IU) was demonstrated in SDAT patients than in MID and healthy subjects (p < 0.001). A significant inverse correlation between the percent increase of NK cytotoxicity after IFN-γ and the Mini Mental State Examination score (p < 0.001) was also demonstrated in patients with SDAT. Our data might suggest a cytokine-dependent mechanism of NK activation in SDAT associated with the neuroimmune hypothesis of the dis

ISSN:1420-8008    

DOI:10.1159/000106648

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In this study a representative sample of German acute care hospitals is used to describe the effects of dementia within acute care hospitals. Data from hospital patients above age 60 with the diagnosis dementia (ICD 290, 293, 294 and 310), collected over an observation period of 12 years, are compared with nondemented hospital patients at the same ages. The differences in the average length of stay between demented and nondemented patients are only relatively small in German acute care hospitals. The degree of multimorbidity is higher and hospital infections are more frequent for demented patients. The main differences occur with mortality: demented inpatients of both sexes experience a hospital mortality which is about twice as high as for nondemented patients at the same ages.

ISSN:1420-8008    

DOI:10.1159/000106649

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Alzheimer''s disease (AD) and vascular dementia (VaD) share several features such as overactivation of microglial cells, damage induced by free radicals, glutamate and calcium overload. Propentofylline (HWA 285) has shown beneficial effects on all of these common elements, thus favouring its use in both subtypes of dementia. In a multinational, randomized, 12-month, double-blind, parallel-group study 260 out-patients with mild to moderate AD or VaD received 300 mg propentofylline (n = 129) or placebo (n = 131) three times daily 1 h before meals. The efficacy was tested at four independent rater levels (physician, psychologist, relative and patient) with assessments covering three major domains of dementia (global function, cognitive function and activities of daily living). After 12 months, the total patient population showed statistically significant treatment differences in favour of propentofylline for the global measures of dementia (Gottfries-Bråne-Steen scale, GBS, p = 0.001; Clinical Global Impressions, CGI, item I: p = 0.004, item II: p = 0.072) as well as for the cognitive measures (Syndrome Short Test, SKT, p = 0.002) and Mini-Mental State Examination (p = 0.001). The activities of daily living also showed a significant treatment difference in favour of propentofylline (p = 0.002). No significant treatment differences were found for rating scales performed by the patients. At month 12, VaD patients showed treatment differences in favour of propentofylline for the GBS total score (p = 0.006), CGI item I (p = 0.004), GGI item II (p = 0.044) and SKT (p = 0.028). Treatment differences for AD patients were all in favour of propentofylline and reached statistical significance for the SKT (p = 0.018). Propentofylline showed a good safety profile with respect to adverse events, vital signs, ECG and laboratory changes

ISSN:1420-8008    

DOI:10.1159/000106650

出版商:S. Karger AG    

年代:1997

数据来源: Karger