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M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Specific role for protein kinase C alpha in the constitutive and regulated secretion of amyloid precursor protein in human skin fibroblasts.

Reduced levels of protein kinase C alpha (PKC alpha) seems to be related to an altered amyloid precursor protein (APP) secretion in fibroblasts from Alzheimer's disease (AD) patients. In this report we used a specific inhibitor of PKC alpha (Gö-6976), to investigate the role of PKC alpha in the basal and phorbol esters regulated secretion of soluble APP (sAPP) in human fibroblasts derived from healthy aged volunteers. Treatment with Gö-6976 alone reduced basal secretion by a maximum of 39%, compared to untreated cells, suggesting the partial dependence of constitutive APP secretory pathway on PKC alpha enzyme. Moreover Gö-6976 treatment completely abolished the effect of phorbol-esters mediated PKC stimulation on sAPP release, suggesting that PKC alpha is the only PKC isoform involved in controlling the secretion of sAPP in human fibroblasts.

Aged↗
PubMed1998

Melanin-concentrating hormone system in the brain of the lungfish Protopterus annectens.

The neurochemical anatomy of the lungfish brain is of particular interest, because many features in these animals might be representative of the common ancestor of land vertebrates. In the present study, we have investigated the localization and biochemical characteristics of melanin-concentrating hormone (MCH)-immunoreactive material in the central nervous system of the African lungfish, Protopterus annectens. The most prominent group of MCH-immunoreactive cell bodies was found in the dorsal hypothalamus. Additional groups of MCH-immunoreactive perikarya were detected in the telencephalon within the medial and dorsal pallium, the medial subpallium, and the ventral part of the lateral subpallium. Brightly immunofluorescent nerve fibers were seen in the anterior olfactory nucleus, the ventral part of the medial pallium, the medial subpallium, and the anterior preoptic area. In the diencephalon, the hypothalamus and the medial region of the dorsal thalamus exhibited a dense accumulation of fibers. MCH-immunoreactive fibers were also found in the tectum and the tegmentum of the mesencephalon and within the reticular formation of the rhombencephalon. In the pituitary, several small groups of cells of the intermediate lobe showed a bright fluorescence. Reversed-phase high-performance liquid chromatography (HPLC) analysis of diencephalon and pituitary extracts resolved a major MCH-immunoreactive peak that coeluted with synthetic salmon MCH. The distribution of MCH in the brain of P. annectens suggests that, in lungfishes, this peptide may exert neuromodulator or neurotransmitter functions. The presence of MCH-like immunoreactivity in the intermediate lobe of the pituitary indicates that, in dipnoans, MCH may also act as a typical pituitary hormone.

Animals↗
PubMed1998

Behavioral disorders in Alzheimer disease: a transcultural perspective.

OBJECTIVES: To compare 2 samples of patients with Alzheimer disease (AD), from Italy and the United States, in order to determine transcultural differences in the manifestation of noncognitive symptoms. To analyze the concurrent validity, internal consistency reliability, between-rater reliability, and test-retest reliability of the Neuropsychiatric Inventory Scale (NPI). METHODS: The NPI was given to 50 Italian and 50 US patients with AD. To demonstrate the validity and reliability of the Italian version of the instrument, several different methods of analysis were used. The total score on the NPI and the score of single items in the different stages of the disease were compared in the 2 samples of patients. RESULTS: A high level of internal consistency reliability was confirmed, the between-rater reliability was very high, and the test-retest reliability was significantly correlated. Apathy was the most frequently recorded behavior in the Italian sample. Five of 10 NPI item scores showed a significant relation with the Mini-Mental State Examination scores in both samples. The Italian patients showed an increasing and significantly higher mean NPI total score at all levels of dementia severity when compared with the US patients. The scores on some NPI subscales, such as apathy, aberrant motor behavior, disinhibition, and agitation, were significant higher in Italian patients at different levels of severity covarying with educational level. CONCLUSIONS: These results indicate that NPI is a reliable instrument with which to study transcultural differences in the presentation of neuropsychiatric disturbances in patients with AD. The described similar pattern of behaviors between Italians and US patients with AD suggests a biological origin of the disorders. However, cultural influences must be taken in account when the focus of the study is on psychopathological aspects of dementia.

Aged↗
PubMed1998

Differential level of platelet amyloid beta precursor protein isoforms: an early marker for Alzheimer disease.

OBJECTIVE: To determine whether a differential level of platelet amyloid beta precursor protein (APP) isoforms is specifically related to Alzheimer disease (AD) and whether it shows a correlation with the progression of clinical symptoms. DESIGN: After subjects were grouped according to diagnosis and severity of dementia, APP isoform levels in platelets were compared. SETTING: University medical centers. PATIENTS: Thirty-two patients who fulfilled diagnostic criteria for probable AD, 25 age-matched control subjects, and 16 patients with non-AD dementia. MAIN OUTCOME MEASURE: The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. Messenger RNAs for APP transcripts were also evaluated by means of reverse transcriptase polymerase chain reaction. RESULTS: The ratio between the intensity of the 130-kd and 106- to 110-kd APP isoforms was significantly lower in the AD group (0.31 +/- 0.15, mean +/- SD) compared with both controls (0.84 +/- 0.2) and non-AD subjects (0.97 +/- 0.4). The ratio of platelet APP isoforms in patients with AD grouped by Clinical Diagnostic Rating score significantly correlated with the severity of the disease (Pearson correlation coefficient, followed by Bonferroni correction, P = .01). Reverse transcriptase polymerase chain reaction experiments showed that APP transcripts in all experimental groups were equally expressed. CONCLUSIONS: The pattern of platelet APP isoforms is specifically altered in patients with AD. In addition, the alteration of platelet APP isoforms shows a positive correlation with the progression of clinical symptoms, supporting the possibility to consider this peripheral parameter as a marker of progression of the disease. These alterations are not related to abnormalities of APP isoforms messenger RNAs in platelets.

Adult↗
PubMed1998

Depressive symptoms of Alzheimer caregivers are mainly due to personal rather than patient factors.

OBJECTIVES: To investigate the predictors of caregiver's depressive symptoms in a sample of community-dwelling Alzheimer's patients. DESIGN: A cross-sectional study was conducted in an Alzheimer's unit specifically devoted to the care of demented patients in Brescia Province (Italy). One hundred and three dyads were consecutively recruited between July 1994 and July 1995. Caregivers were sons/daughters (65%) or husbands/wives; mean age was 54.6 +/- 13.2. Alzheimer's patients Mini Mental State Examination score was 11.3 +/- 8.3; patients were equally distributed among disease severity levels. The following variables have been collected: (a) background and context variables (caregiver's age, gender, marital status, education, relationship and cohabitation with the patient, employment status, satisfaction with household income);(b) caregiver's personal resources (health, social relationships and social interactions, formal supports use, assistance and vigilance); (d) primary stressors (patient's age and gender, cognitive status, functional status, frequency of behavioural disturbances). Caregiver's depressive symptoms represented the main outcome measure. RESULTS: Being husband or wife, low self-rated health and caregiving competence, high numbers of hours for assistance and patient's behavioural disturbances and younger age were associated caregiver's depressive symptoms. With multivariate analysis only relationship to the patient, caregiver's health and competence were independent predictors of caregiver's depressive symptoms. CONCLUSION: Factors related to the caregiver--relationship, health and competence--rather than to the patient constitute the main risk factors for caregiver's depressive symptomatology.

Adult↗
PubMed1998

Visual and spatial perception in the early phase of Alzheimer's disease.

A battery of visuospatial perception tests was administered to 27 mild probable Alzheimer's disease (AD) patients; 21 were reassessed after 8 months. At the first evaluation, AD patients were impaired only in an object-naming task. After 8 months, the performance in the subtests of object perception was unchanged, while there was a significant decline in the total score of the items tapping space perception. A significant worsening was also observed in the Rey's figure copy score and was correlated with the decrease in the spatial perception score. This study confirms that an impairment in visual perceptual tests requiring access to semantic and lexical knowledge is present in the earliest phase of AD, whereas visuospatial and constructional impairments became evident only later. This pattern of progression may represent the clinical correlate of increasing pathological involvement of posterior associative cortex.

Aged↗
PubMed1998

Modulation of neurosteroid synthesis/accumulation by L-ascorbic acid in rat brain tissue: inhibition by selected serotonin antagonists.

We have investigated the possibility that the synthesis/accumulation of neurosteroids, i.e., brain-produced steroids putatively endowed with modulatory actions in the CNS, is regulated by monoaminergic receptor-mediated mechanisms. In minces of rat brain cortex, L-ascorbic acid concentration-dependently (0.07-1.0 mM) increases the levels of pregnenolone, allotetrahydrodeoxycorticosterone, and dehydroepiandrosterone. This effect of L-ascorbic acid is region-dependent: in hippocampus, progesterone and allopregnanolone are also increased, whereas dehydroepiandrosterone is unchanged, and in corpus striatum only progesterone is increased significantly. 5-Hydroxytryptamine (10 microM), 1-(3-chlorophenyl)piperazine (1.0 microM), and 5-methoxytryptamine (0.4 microM) mimic the effect of L-ascorbic acid, whereas a pretreatment with p-chlorophenylalanine (400 mg/kg i.p., 2 days) reduces the amplitude of the L-ascorbic acid effect on brain cortical neurosteroids. The effect of L-ascorbic acid is blocked by the nonselective serotonin antagonists methiothepin, clozapine, methysergide, and pizotifen, but not mesulergine, spiperone, MDL 72222, and DL-propranolol, nor by the catecholaminergic receptor antagonists prazosin and S(-)-sulpiride. L-Ascorbic acid is not additive with dibutyryl-cyclic AMP and, furthermore, the inhibition of adenylate cyclase by MDL 12330A, but not of phospholipase C by U-73122, markedly attenuates the L-ascorbic acid-induced increase of pregnenolone in rat brain cortical minces. Together these data suggest that L-ascorbic acid plays a role in the modulation of neurosteroidogenesis, presumably by favoring the activation of the purported serotonin type 6 receptor by endogenous serotonin.

Adenylyl Cyclase Inhibitors↗
PubMed1998

LEIPAD, an internationally applicable instrument to assess quality of life in the elderly.

A questionnaire to assess quality of life in the elderly was developed under the auspices of the European office of the World Health Organization. Stages in construction of the instrument, which was designed for international application, particularly at the primary level, are described. The latest version of the questionnaire is composed of 49 self-assessment item, 31 of which can be grouped into 7 subscales: Physical Function, Self-Care, Depression and Anxiety, Cognitive Functioning, Sexual Functioning, and Life Satisfaction. The remaining 18 items serve as moderators for assessing the influence of social desirability factors and personality characteristics on the individual scores for the 7 core instrument subscales. The questionnaire has been administered to 586 individuals aged 65 years and over recruited in communities in Italy (Padua and Brescia), the Netherlands (Leiden), and Finland (Helsinki). The main psychometric characteristics of the instrument, together with its concurrent validity with the Rotterdam Questionnaire, are illustrated.

Aged↗
PubMed1998

Validity of direct assessment of functional status as a tool for measuring Alzheimer's disease severity.

OBJECTIVE: to assess the validity of the Direct Assessment of Functional Status (DAFS) performance-based functional scale for the staging of dementia severity by comparing it with established clinical, functional and cognitive scales. PATIENTS AND METHODS: 93 consecutive Alzheimer's disease patients underwent DAFS. Socio-demographic variables, cognitive status (Mini-Mental State Examination; MMSE), global disease severity (Clinical Dementia Rating; CDR), disease duration, physical performance (Physical Performance Test, PPT) and functional status (as reported by the primary caregiver) were also recorded and basic (B) and instrumental (I) activities of daily living (ADL) assessed. RESULTS: a significant correlation was found between DAFS and MMSE (Pearson's r = 0.60; P < 0.01), PPT (r = 0.54; P < 0.01) and CDR (Spearman correlation coefficient: -0.48; P < 0.01). A mild, significant correlation was found between DAFS score and daily function as reported by the primary caregiver (r = -0.30 for BADL and r = - 0.27 for IADL). On multiple regression analysis, only MMSE and PPT were independently associated with the DAFS score, explaining 56% of DAFS total variance. ADL scales did not independently contribute to DAFS variance. A multivariate regression model of the association of DAFS with CDR showed that the association was significant even after adjustment for MMSE and PET, suggesting that DAFS scores provide additional information on dementia severity. CONCLUSION: DAFS is a valid tool for the assessment of dementia severity, capturing cognitive and physical aspects of disability.

Activities of Daily Living↗
PubMed1998

Special care units for demented patients: a multicenter study.

The local government of Regione Lombardia, Italy, recently (1994) funded a clinical and research project specifically devoted to dementia (Piano Alzheimer). A central role in this project has been reserved for the special care units (SCUs) for demented patients with behavioral disturbances. In order to evaluate their effectiveness, eight SCUs took part in this study. A specifically designed care program, focusing on environment and staff, was implemented in each SCU. Cognitive, functional, and somatic health status, and use of psychotropic drugs and of physical restraints were assessed at baseline, and after 3 and 6 months in 55 consecutively admitted patients. The data show an overall reduction in behavioral disturbances and a decreased use of psychotropic drugs and physical restraints.

Aged↗
PubMed1998

Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease.

Alterations in amyloid precursor protein (APP) metabolism, calcium regulation, oxidative metabolism, and transduction systems have been implicated in Alzheimer's disease (AD). Limitations to the use of postmortem brain for examining molecular mechanisms underscore the need to develop a human tissue model representative of the pathophysiological processes that characterize AD. The use of peripheral tissues, particularly of cultured skin fibroblasts derived from AD patients, could complement studies of autopsy samples and provide a useful tool with which to investigate such dynamic processes as signal transduction systems, ionic homeostasis, oxidative metabolism, and APP processing. Peripheral cells as well as body fluids (i.e., plasma and CSF) could also provide peripheral biological markers for the diagnosis of AD. The criteria required for a definite diagnosis of AD presently include clinical criteria in association with histopathologic evidence obtained from biopsy or autopsy. Thus, the use of peripheral markers as a diagnostic tool, either to predict or at least to confirm a diagnosis, may be of great importance.

Alzheimer Disease↗
PubMed1998

The prevalence of apoE-epsilon4 in Alzheimer's disease is age dependent.

The epsilon4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. However, other yet unidentified factors might be involved. It has been suggested that the epsilon4 allele might be relatively less relevant in Alzheimer's disease with onset before age 60 and after age 80. The aim was to evaluate the association of the epsilon4 allele with Alzheimer's disease across a wide range of ages at onset. 156 patients with age at onset between 46 and 89 and 120 cognitively unimpaired subjects aged 53 to 89 as controls were studied. Age at onset in the cases and age in the controls were stratified into six groups (60 and younger, 60 to 64, 65 to 69, 70 to 74, 75 to 79, and 80 and older). Multivariable sex adjusted probit regression analysis was used to model epsilon4 prevalences in cases and controls across age. The sex adjusted relation of epsilon4 with age in controls was slightly negative with prevalence of 0.16 in the youngest and 0.09 in the oldest age groups. The sex adjusted relation in cases with Alzheimer's disease had a bell shaped curve with prevalence of 0.23 in the youngest age group, rising to 0.54 and 0.51 in the age groups 65 to 69 and 70 to 74, and decreasing to 0.12 in the oldest age group. It is concluded that the relation of the epsilon4 allele with Alzheimer's disease is age dependent, indicating that other risk factors might be relevant in the younger and older ages.

Age Factors↗
PubMed1998

Object and action naming in Alzheimer's disease and frontotemporal dementia [see comment].

To assess noun and verb processing in different dementia types, we tested object and action naming in three groups of subjects: probable Alzheimer's disease (AD) with mild to moderate dementia; age- and education-matched normal subjects; and a group of frontotemporal dementia (FTD) patients. AD and FTD patients were impaired in naming compared with control subjects; action naming was more severely impaired. However, the discrepancy between object and action naming was significantly greater in FTD than in AD patients, independent of the severity of dementia or of overall language impairment. The latter finding is compatible with the hypothesis that the frontal lobe plays a crucial role in action naming. A relatively selective impairment in action naming might be a characteristic neuropsychological feature of FTD.

Aged↗