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Biomedical subjects

A Bianchetti

Publications and source records attributed to A Bianchetti.

At least 19 recordsLinked to original sources
PubMed1999

Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease.

OBJECTIVE: To describe atrophic changes of the hippocampus and entorhinal cortex in frontotemporal dementia (FTD) and compare them with those of AD. BACKGROUND: The medial temporal lobe shows atrophic changes early in the course of AD, but whether these changes are specific to AD or occur in other degenerative dementias, and to what extent, is unclear. METHODS: The authors measured the volumes of the left and right hippocampus and entorhinal cortex from MR images (1.5 T, 2-mm-thick slices) in 12 patients with FTD, 30 with AD, and 30 elderly control subjects. RESULTS: In FTD patients, the left and right hippocampus (16% and 21% tissue loss) and the entorhinal cortex (28% and 27% loss) were more atrophic than the control subjects. Atrophy of the hippocampus in FTD was less severe than in AD, but atrophy of the entorhinal cortex was equally severe. Greater hippocampal and entorhinal cortex atrophy was present in the most severe patients in both groups (as high as a 49% tissue loss). The sensitivity of the hippocampus and the entorhinal cortex to discriminate FTD patients from control subjects was low (49% and 52%, respectively; specificity set at 90%), whereas hippocampal volumes could better differentiate AD patients from control subjects (80% sensitivity). CONCLUSIONS: At variance with AD, detectable in vivo atrophy of the hippocampus might not be an early event in FTD. Differential patterns of atrophy might help in the diagnostic process of the degenerative dementias.

Age Factors↗
PubMed1999

Insight in dementia: when does it occur? Evidence for a nonlinear relationship between insight and cognitive status.

Lack of insight or impaired awareness of deficits in patients with dementia is a relatively neglected area of study. The aim of this study was to evaluate insight in a group of demented patients with two assessment scales and to assess their relationship with the cognitive level of disease severity. Sixty-nine consecutive patients affected by Alzheimer's disease (n = 37) and vascular dementia (n = 32) with a wide range of cognitive impairment (MMSE = 17.0 +/- 6.4) were recruited. Insight was evaluated with the Guidelines for the Rating of Awareness Deficits (GRAD)--specifically targeted to memory deficits--and the Clinical Insight Rating scale (CIR), evaluating a broader spectrum of insight (reason for the visit, cognitive deficits, functional deficits, and perception of the progression of the disease). In the whole sample, GRAD and CIR were significantly associated with MMSE (Spearman's coefficient = .51, p < .001; and r = -.55, p < .001) and with Clinical Dementia Rating scale (-.57, p < .001; and r = .57, p < .001) respectively. The shape of the relationship of MMSE with CIR and GRAD scales was assessed with spline smoothers suggesting that the relationship follows a trilinear pattern and is similar for both scales. Insight was uniformly high for MMSE scores > or = 24, showed a linear decrease between MMSE scores of 23 and 13, and was uniformly low for MMSE scores < or = 12. The trilinear model of the association between insight and cognitive status reflects more closely the observable decline of insight and can provide estimates of when the decline of insight begins and ends.

Activities of Daily Living↗
PubMed1999

Contrasting results between caregiver's report and direct assessment of activities of daily living in patients affected by mild and very mild dementia: the contribution of the caregiver's personal characteristics.

OBJECTIVE: To determine the level of agreement between the primary caregiver's report on patient activities of daily living (ADLs) and ADLs assessed directly in a sample of patients affected by very mild and mild dementia and to assess whether this agreement is influenced by the caregiver's depressive symptoms and burden. PATIENTS AND METHODS: Data were obtained from the baseline sample of the Mild Dementia Longitudinal Study, consisting of 111 consecutive patients affected by dementia with very mild to mild functional impairment (grades .5 and 1 on the Clinical Dementia Rating Scale). As is usual for patients referred to our Alzheimer's Unit, anamnestic, cognitive, functional and behavioral information are collected from the primary caregiver. Along with sociodemographic characteristics, caregivers' depressive symptoms (Beck Depression Inventory Scale) and burden (Nowak and Guest's Caregiver Burden Inventory Scale) were also evaluated. Patients underwent a performance-based assessment of the activities of daily living (DAFS) and direct assessment of physical function with the Physical Performance Test (PPT). Caregiver's report and direct observation have been compared for the following ADLs: dressing, toileting, walking, telephone use, shopping, and money use. Discriminant analyses were conducted to examine the degree of agreement between caregiver-report functional status and performance-based measures and whether additional agreement is attributable to caregiver's burden and depressive symptoms. RESULTS: The strength of the association between the caregiver's report and performance-based measures of ADLs is high for motor performance (walking), moderate to good for dressing, but only moderate for telephone, money use, and shopping. No association was found for toileting. The discrepancies between caregiver report and performance-based assessment were influenced substantially by the burden caused by demands and restrictions on a caregiver's time. CONCLUSIONS: With the exception of motor performance (walking), the caregiver's report and the performance-based assessment of functional status measure different aspects of a patient's functional status. Contrasts between the caregiver's report and observed ADL performance in mildly and very mildly demented patients are influenced by the caregiver's burden.

Activities of Daily Living↗
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

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

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

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↗
PubMed1997

Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients.

Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P < 0.05). The basal oxygen consumption rate (QO2) and the response to an uncoupler of oxidative phosphorylation did not differ between AD and control fibroblasts. The QO2 of AD fibroblasts was more susceptible (P < 0.05) to inhibition by azide in the range 0.5-5 mM. The basal intracellular pH (pHi) in AD fibroblasts was significantly more acidic than in control ones. The results support the hypothesis that subtle dysfunctions of oxidative energy-producing processes are present in fibroblasts from sporadic AD patients. The alterations observed scantly influence the fibroblasts functioning even in stressful conditions; however in tissues, such as the brain, that rely heavily on oxidative metabolism for their function, similar alterations may trigger molecular mechanisms leading to cell damage.

Aged↗
PubMed1997

Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells.

The present study investigates the influence of energy related metabolic stress on amyloid precursor protein (APP) non-amyloidogenic secretory processing in COS cells. The effect of glucose deprivation on soluble APP (sAPP) secretion has been evaluated: incubation of COS cells with 50 mM 2-deoxy-D-glucose (2-DG) in glucose free medium was able to reduce sAPP secretion (-26%). Sodium azide (NaN3), an inhibitor of cytochrome c oxidase (complex IV of the mitochondrial electron transfer chain) decreased sAPP release in a concentration dependent way (maximum -75%). Treatment of COS cells with the antioxidant glutathione (GSH) fully antagonized the inhibitory effect of azide (1 mM) and elicited sAPP release over basal level. These results suggest that the inhibition of energy metabolism can influence APP processing leading to a decreased secretion of non-amyloidogenic fragments of APP.

Amyloid beta-Protein Precursor↗