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S Sorbi

Publications and source records attributed to S Sorbi.

At least 19 recordsLinked to original sources
PubMed2005

p66(shc) is highly expressed in fibroblasts from centenarians.

p66(shc-/-) mice exhibit prolonged lifespan and increased resistance to oxidative and hypoxic stress. To investigate p66(shc) involvement in human longevity, p66(shc) mRNA and protein were evaluated in fibroblasts from young people, elderly and centenarians, exposed to oxidative or hypoxic stress. Unexpectedly, centenarians showed the highest basal levels of p66(shc). Oxidative stress induced p66(shc) in all samples. At variance, hypoxic stress caused p66(shc) reduction only in cells from centenarians. These changes occurred in absence of any modification of p66(shc) promoter methylation pattern. Intriguingly, in cells from centenarians, p66(shc) induction was affected by p53 codon 72 polymorphism. Thus, cells from centenarians present a peculiar regulation of p66(shc), suggesting that its role in mammalian longevity is more complex than previously thought.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment.

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.

Aged↗
PubMed2005

Metabolic interaction between ApoE genotype and onset age in Alzheimer's disease: implications for brain reserve.

BACKGROUND: Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (<65 years) in patients carrying the E4 allele is associated with greater cerebral metabolic (regional cerebral metabolic rate of glucose utilisation, rCMRgl) reduction. METHODS: AD patients, divided into early (EOAD; 27 patients) and late onset (LOAD; 65 patients) groups, both groups balanced as to the number of E4 carriers (E4+) and non-carriers (E4-), and matched controls (NC; 35 cases) underwent (18)F-FDG PET ([(18)F]fluorodeoxyglucose positron emission tomography) scanning. SPM'99 software was used to compare AD patients to NC and to perform a two way ANOVA with onset age and ApoE genotype as grouping factors. Results were considered significant at p<0.001, uncorrected. RESULTS: AD patients demonstrated rCMRgl reductions compared to NC, with rCMRgl lower in association cortex and relatively higher in limbic areas in EOAD compared to LOAD subjects. rCMRgl was lower in the anterior cingulate and frontal cortex for E4+ compared to E4- subjects. A significant onset age by ApoE interaction was detected in the hippocampi and basal frontal cortex, with EOAD E4+ subjects having the greatest rCMRgl reduction. CONCLUSIONS: The interactive effects of early onset age, possibly reflecting lower brain reserve, and ApoE E4 allele, possibly leading to greater tissue damage, lead to reduced tolerance to the pathophysiological effects of AD in key brain regions.

Age of Onset↗
PubMed2004

MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET.

OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.

Aged↗
PubMed2004

Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment.

OBJECTIVE: To assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Conventional MR was acquired in 41 patients with RR MS and 16 demographically matched normal control subjects (NCs). An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and neuropsychological scores was assessed. RESULTS: Neuropsychological assessment allowed for the identification of 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS sample showed lower values of normalized cortical volumes (NCVs) than did the NC group (p = 0.01). Upon grouping of MS patients according to cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs. Moreover, there were positive correlations between NCV values and measures of verbal memory (r = 0.51, p = 0.02), verbal fluency (r = 0.51, p = 0.01), and attention/concentration (r = 0.65, p < 0.001) in MS-ci patients. Furthermore, NCV values were decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the neuropsychological measures correlated to NCV values in the MS-cp patient group. CONCLUSIONS: Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Adult↗
PubMed2004

Combined family trio and case-control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa.

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample.

Alleles↗
PubMed2004

Validation of the Guidelines for the Diagnosis of Dementia and Alzheimer's Disease of the Italian Neurological Society. Study in 72 Italian neurological centres and 1549 patients.

The objective of this study was to verify the adherence of Italian family physicians and neurologists to the Guidelines on Diagnosis of Dementia of the Italian Society of Neurology. A multicentre survey was carried out, in 72 neurological centres. The centres included at least 15 consecutive subjects suspected of having a dementia. The adherence of family physicians to the guidelines was poor. Neurologists performed a complete neuropsychological evaluation in a minority of the cases. Patients who had a decrease of Mini Mental Status Examination scores after six months higher than or equal to 4 were more represented among those patients for whom one or more recommendations were not respected. In Italy the adherence to the Guidelines on Diagnosis of Dementia and AlzheimerValidation studys Disease of the Italian Society of Neurology is very poor for family physicians (GPs) and satisfactory, albeit improvable, on the part of neurologists. Respect for the guidelines might improve the outcome of patients with dementia.

Aged↗
PubMed2004

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death.

A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg+) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro+). At variance, the difference in apoptosis susceptibility between Arg+ and Pro+ is not significant when cells from 30-year-old people are studied. Further, we found that Arg+ and Pro+ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg+ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro+ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.

Adult↗
PubMed2004

Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease.

OBJECTIVES: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon 4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods. METHODS: Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p<0.001, corrected for cluster extent) and also to compare between the subgroups (p<0.001, uncorrected). RESULTS: No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 non-carriers. CONCLUSIONS: The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.

Aged↗
PubMed2003

Brain metabolic differences between sporadic and familial Alzheimer's disease.

This FDG-PET study with SPM99 compared 46 patients with sporadic Alzheimer disease (SAD) to 40 patients with familial AD (FAD) and to 35 matched controls. AD groups had equivalent metabolic (METglu) reductions in several cortical and limbic areas with respect to the controls. Patients with FAD showed decreased METglu in the posterior cingulate, parahippocampal, and occipital cortex as compared to the patients with SAD (p < 0.001). Genetic factors lead to phenotypic differences in AD.

Age of Onset↗
PubMed2003

Interleukin-1B polymorphism is associated with age at onset of Alzheimer's disease.

Interleukin-1alpha (IL-1alpha) and IL-1beta are two pro-inflammatory cytokines involved in the pathogenesis of Alzheimer's disease (AD). The genes coding for IL-1alpha (IL-1A) and for IL-1beta (IL-1B) are clustered in chromosome 2q14-2q14.2. In a previous work, we investigated the role of IL-1A promoter polymorphism (-889 position) in AD pathogenesis: IL-1A -889 TT genotype was associated with sporadic early onset AD. We now report the study on polymorphism of exon 5 IL-1B in position +3953, the nearest polymorphism to -889 IL-1A. We found that the genotype distribution of IL-1B +3953 varied significantly between patients with early and late onset of AD (P<0.0001). Patients carrying IL-1B +3953 CT or TT genotypes had 4 or 5 years anticipation of AD onset (P=0.0034; odds ratio for early onset, 3.01) and 7 years anticipation if they also carried the IL-1A -889 TT genotype (P<0.0001; odds ratio for early onset, 7.4). These data further support a role for inflammation-related genes in AD or indicate linkage disequilibrium with an unknown chromosome 2 locus.

Aged↗
PubMed2003

Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort.

To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.

Adult↗
PubMed2003

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

Adult↗
PubMed2002

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Adolescent↗
PubMed2001

The C677T methylenetetrahydrofolate reductase mutation is not associated with Alzheimer's disease.

The methylenetetrahydrofolate reductase (MTHFR) gene has been recently considered as a candidate gene for Alzheimer's disease (AD). MTHFR is a key enzyme in the metabolism of homocysteine and elevated levels of that amino acid have been associated to Vascular Dementia and AD. A T-->C transition at codon 677 produces a thermolabile type of the enzyme. However, contrasting results on the distribution of the MTHFR C677T common polymorphism in AD have been published. We analyzed the distribution of the MTHFR and apolipoprotein E (APOE) polymorphisms in Italian patients with sporadic AD. The distribution of the C677T polymorphism did not differ in AD and controls. Our data suggest that the MTHFR polymorphism does not contribute to genetic susceptibility in Italian sporadic AD and does not mitigate the effect of ApoE epsilon4 allele on AD risk.

Adult↗
PubMed2001

Association between 5-HT(2A) receptor polymorphism and psychotic symptoms in Alzheimer's disease.

BACKGROUND: The aim of this study is to analyze the segregation of the 102T/C polymorphism in the serotonin 2A receptor gene in patients affected by sporadic and familial Alzheimer's disease (FAD) with and without psychotic symptoms. METHODS: The polymorphism was analyzed in 275 subjects. A semistructured interview was used to obtain information about delusions, hallucinations, and other specific behavioral signs occurring during the disease. RESULTS: Fifty-two percent of AD patients with psychotic symptoms were homozygous for the C102 allele, as compared with 6.9% of AD patients without psychosis. Similarly, the C102/C102 genotype was significantly more frequent in FAD patients with psychosis than in FAD patients without (46.5% vs. 7.8%). CONCLUSIONS: Our data strongly confirm and extend to FAD previous studies suggesting that the genetic variation at this locus is associated with prominent psychotic features in AD and that the 102C allele could play an important role in late-onset AD.

Aged↗