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Biomedical subjects

A Bianchetti

Publications and source records attributed to A Bianchetti.

At least 73 records · Page 4Linked to original sources
PubMed1996

Executive dysfunction in early Alzheimer's disease.

Twenty five patients with probable mild Alzheimer's disease were assessed for deficits in executive functioning and the impact of these deficits on performance in other neuropsychological domains. The Wisconsin card sorting test, the release from proactive interference paradigm, the verbal fluency test, and the Stroop test were adopted to classify patients with (AD+) and without (AD-) executive deficits. Seven of the patients showed an impairment in executive function (AD+), defined as a performance below the cut off score in at least two of these tests. There were no significant differences in clinical assessments, demographic features, or other cognitive functions between patients. Executive dysfunction may be an early additional feature in a subgroup of patients with mild Alzheimer's disease. Impairment on frontal lobe tests does not seem to be related to the severity or duration of disease, or to a different pattern of impairment in other cognitive domains.

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PubMed1996

Brain atrophy in frontotemporal dementia.

OBJECTIVES: To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS: Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS: Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION: A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia.

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PubMed1996

Risk of mortality and institutionalization in demented patients with delusions.

Delusions are a common symptom during the course of dementia. Despite their clinical relevance, however, it is still unclear whether they are of prognostic value. This longitudinal study involving, at baseline, 99 demented Alzheimer disease (AD) and multi-infarct dementia (MID) patients, investigates the risk of mortality and institutionalization at 2 years after discharge from a dementia unit in patients with and without delusions at baseline. Results indicate that the presence of delusions is a significant predictor of future institutionalization (odds ratio 3.6, confidence interval 1.3-9.6), even when confounding factors such as age, educational level, and severity of cognitive and functional impairment are statistically controlled. No significant impact on survival was found.

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PubMed1996

Fibroblasts of patients affected by Down's syndrome oversecrete amyloid precursor protein and are hyporesponsive to protein kinase C stimulation.

The present study investigates the ability of the pharmacologic activation of protein kinase C (PKC) to modulate amyloid precursor protein (APP) secretion in human skin fibroblasts from patients affected by Down's syndrome (DS). We assessed DS subjects at the Hospital Institute of Sospiro, Cremona, and at the Alzheimer's Disease Unit of the Sacred Heart Hospital in Brescia, and we subdivided them into nondemented (NDS) and demented (DDS) patients. All DS patients were trisomy 21 karyotype. DS fibroblasts had an increased content of APP immunoreactive material as revealed by immunocytochemistry analysis. The basal secretion of soluble APP was higher (+94.6%) in Down's cells with respect to controls. The observation on the fibroblasts prepared from DS is consistent with these patients' possessing an extra copy of the APP gene (mapped on chromosome 21) leading to increased APP expression. Phorbol-12,13-dibutyrate (PdBu, 9 to 150 nM) treatment promoted a dose-dependent increase of secreted APP in the conditioned medium of control fibroblasts. The peak response (+102.2%) was attained using 150 nM PdBu. In Down's fibroblasts, PdBu stimulated APP secretion already maximally at low concentrations (9 nM), but the peak response, due to the higher basal release, was lower on a percentage basis (+16.4%) than in control fibroblasts. The results indicate that in Down's fibroblasts the mechanisms controlling APP release are at least quantitatively altered. In addition, these results suggest caution when using information obtained from Down's patients to model Alzheimer's disease biochemical defects.

Adult↗
PubMed1996

Apolipoprotein E.

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Apolipoproteins E↗
PubMed1996

Linear measures of atrophy in mild Alzheimer disease.

PURPOSE: To assess the sensitivity of linear measures of brain atrophy in the diagnosis of Alzheimer disease (AD) in the early stages. METHODS: Linear measures of regional frontal (Bifrontal index, interhemispheric fissure width), medial temporal lobe (interuncal distance, minimum thickness of the medial temporal lobe), and hippocampal (hippocampal height, width of the choroid fissure, width of the temporal horn) atrophy were made on magnified MR images obtained in 46 patients with AD (33 with mild severity and 13 with moderate severity) and in 31 control subjects. Gaussian modeling was used to compute sensitivity with specificity set at 95%. Discriminant analysis was used to identify measures independently contributing to the ability to discriminate AD patients from control subjects. RESULTS: The measure with the best sensitivity in discriminating AD patients from control subjects was the width of the temporal horn. A compound measure of width of the temporal horn, width of the choroid fissure, height of the hippocampus, and interuncal distance could discriminate patients with mild AD from control subjects with 86% sensitivity. Cross validation in patients with moderate AD confirmed the usefulness of the model (81% sensitivity). Measures of hippocampal atrophy alone could discriminate patients with mild AD from control subjects with 83% sensitivity; in patients with moderate AD, cross validation produced 87% sensitivity. CONCLUSIONS: Linear measures of hippocampal atrophy can be a useful adjunct in the routine diagnosis of AD, even in its early stages.

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PubMed1996

Delusions.

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PubMed1995

Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts.

The present study shows that cultured fibroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduced response at low concentrations of phorbol-12,13-dibutyrate, with an EC50 twofold higher than control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly be correlated to a specific defect in protein kinase C alpha in fibroblasts from Alzheimer patients.

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PubMed1995

Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer's disease.

A strong association has been described in cross-sectional studies between the epsilon 4 allele of the apolipoprotein E and late-onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the epsilon 4 allele in 62 sporadic LOAD (onset at age 70 and over) patients. Disease progression was estimated retrospectively with the Mini-Mental State Examination (MMSE) amounting to 4.7, 3.8, and 2.2 points per year (sex-adjusted test for trend: p = 0.01) and with the Clinical Dementia Rating (CDR) to 0.76, 0.67, and 0.42 units per year (p = 0.03) in -/-, epsilon 4/-, and epsilon 4/epsilon 4 patients. The proportion of patients with fast progression decreased (p < or = 0.005) and with slow progression increased (p = 0.002) with increasing epsilon 4 gene dose. These findings were confirmed in a smaller sample of 28 patients for whom longitudinal assessments of MMSE were available and when nonlinear progression of the disease was accounted for in a stratified analysis. These data suggest that disease duration might be longer in epsilon 4 carriers and that this might at least partly account for the cross-sectional association between the epsilon 4 allele and LOAD.

Age of Onset↗
PubMed1995

Release from proactive interference in early Alzheimer's disease.

The study analyses the performance of 22 mild Alzheimer's disease (AD) patients on the Release from Proactive Interference (RPI) paradigm with the aim to investigate the relationship of RPI with frontal function. Twenty-one normal elderly subjects, age and education matched, constituted the control group. Patients with AD were found to recall less words on each trial of the RPI than did the controls. The analysis of Proactive Interference (PI) and Release from PI, in AD patients, by using Anova (trial x group), showed a significant effect of trial and group but not a group by trial interaction. These results indicate a similarity between the performance of AD patients and normal controls on the Release from Proactive Interference paradigm. Despite the similar pattern of performance, AD patients were significantly inferior to normal controls with regard to global performance level. The AD patients' scores on "frontal lobe" tests were correlated with an index of RPI (shift condition index). The only significant result was with the number of categories on the Wisconsin Card Sorting Test, suggesting a weak correlation between RPI and "frontal lobe" function.

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PubMed1995

Semantic memory in Alzheimer's disease: an analysis of category fluency.

In order to study the strategies of access to semantic knowledge and the status of semantic representation, we analyzed the performance in a semantic fluency task (Animal naming) of 70 patients with probable Alzheimer's disease (AD), including 40 mild AD patients and 30 moderate-severe AD patients, and 35 matched elderly normal control subjects. The total amount of words produced, their lexical frequency, the number and type of errors, as well as the presence and the type of clusters of related animal names were recorded. AD patients produced less animal exemplars than controls. In addition to a lower total number of clusters, the AD patients showed a strong limitation in clusters' selection, producing a limited number of different clusters. While normal subjects produced several different clusters, only farm animals were clustered by AD patients. When the total amount of words was considered, the mean lexical frequency was higher in the AD group. On the other hand, the words produced within clusters were comparable to terms of lexical frequency and number. These data confirm the impairment of AD patients in category fluency tasks, and suggest a degradation of semantic knowledge as the most likely underlying mechanism.

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PubMed1995

Drug-induced defaecation in rats: role of central 5-HT1A receptors.

1. We investigated the acute effects of 5-hydroxytryptamine (5-HT), and of the 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), buspirone and SR 57746A, on rat faecal pellet output and water content. 2. 5-HT, 8-OH-DPAT, buspirone and SR 57746A, a new selective 5-HT1A receptor agonist, displaced [3H]-8-OH-DPAT from specific binding sites in rat hippocampus membranes (Ki, nM; 1.8, 1.2, 15, 3.1 respectively) and stimulated rat defaecation dose-dependently. SR 57746A and buspirone induced 1 g dry weight of faeces at 1.3 and 6.1 mg kg-1, p.o. (AD1) respectively. 8-OH-DPAT and 5-HT stimulated defaecation after s.c. injection (AD1, 0.07 and 7.5 mg kg-1, respectively). All these agents increased faecal water content. 3. The putative 5-HT1A receptor antagonist, pindolol, injected s.c. or i.c.v., significantly reduced the defaecation induced by systemically administered 8-OH-DPAT, buspirone or SR 57746A, but not 5-HT. 4. Pretreatment with p-chlorophenylalanine (i.p.) or 5,7-dihydroxytryptamine (i.c.v.), according to protocols designed to cause either generalized or CNS-limited 5-HT depletion respectively, also reduced the defaecation induced by buspirone or SR 57746A. 5. No specific 5-HT1A binding sites could be labelled by incubating rat colon membranes with [3H]-8-OH-DPAT, and in vitro preparations of rat colon segments showed no response to 8-OH-DPAT or SR 57746A up to 5 microM. 6. After eight days' repeated daily treatment, complete tolerance developed to the stimulant effects of SR 57746A and buspirone on faecal water content, but not on faecal pellet output. This suggests that faecal mass excretion and water exchange through the gut wall are affected by independent mechanisms.7. The present findings support the involvement of central 5-HTIA receptors in intestinal propulsion and regulation of luminal fluid content, presumably accounting for the drug-induced defaecation in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Delusions and dementia: clinical and CT correlates.

INTRODUCTION: Delusions occur frequently during the course of Alzheimer's disease (AD) and multi-infarct dementia (MID). Their clinical significance and their relationship with progression of disease and involvement of selected cerebral areas are still unclear. The aim of the study was to determine the clinical and CT correlates of delusions in patients with dementia. MATERIAL AND METHODS: A series of 67 probable AD and 32 MID patients, underwent computed tomographic scans, psychometric tests, neurologic and psychiatric examination, and blood and serum tests. RESULTS: Twenty-four patients were found to have delusions during the clinical evaluation. Delusional patients showed a significantly higher age when compared with non-delusional patients. The results of a multiple logistic regression (with stepwise deletion of the redundant variables) of the CT lesions on the presence of delusions, showed that only the presence of isolated white matter lesions in the frontal lobes were significantly related to the occurrence of delusions (Exp B = 3.42; Beta = 1.2; S.E. = 0.6; Sig T = 0.04). Frontal white matter changes were significantly related to delusions when a multiple regression analysis, entering age and total number of lesions at CT scans, was carried out. CONCLUSIONS: We found that focal lesions in the frontal areas were the only variable that appeared to be significantly and independently associated with delusional disorders.

Activities of Daily Living↗