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Biomedical subjects

G Binetti

Publications and source records attributed to G Binetti.

At least 19 recordsLinked to original sources
PubMed2006

Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms.

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Aged↗
PubMed2006

Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment.

BACKGROUND: The diagnosis of mild cognitive impairment (MCI) is clinically unhelpful, as many patients with MCI develop dementia but many do not. OBJECTIVE: To identify clinical instruments easily applicable in the clinical routine that might be useful to predict progression to dementia in patients with MCI assessed in the outpatient facility of a memory clinic. PARTICIPANTS AND METHODS: 52 dementia-free patients (mean (standard deviation) age 70 (6) years; 56% women) with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain magnetic resonance scan with standardised visual assessment of medial temporal atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow-up assessment occurred 15.4 (SD 3.4) months after baseline to detect incident dementia and improvement, defined as normal neuropsychological performance on follow-up. RESULTS: Patients were classified into three groups according to the presence of memory disturbance only (MCI Mem), other neuropsychological deficits (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31% and 47% v 5% and 14% of controls and MCI Oth, p<0.001). 11 patients developed dementia (annual rate 16.5%) and 7 improved on follow-up. The only independent predictor of progression was MTA (odds ratio (OR) 7.1, 95% confidence interval (CI) 1.4 to 35.0), whereas predictors of improvement were the absence of memory impairment (OR 18.5, 95% CI 2.0 to 171.3) and normal MRI scan (OR 10.0, 95% CI 1.7 to 60.2). CONCLUSION: Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia. MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.

Aged↗
PubMed2006

Action and object naming in frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration.

Action naming has been reported to be disproportionately impaired in comparison to object naming in patients with frontotemporal dementia (FTD). This finding has been attributed to the crucial role of frontal cortex in action naming. The investigation of object and action naming in the different subtypes of FTD, as well as in the related conditions of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), may thus contribute to the elucidation of the cerebral correlates of the action-object discrepancy as well as provide clues to the underlying cognitive mechanisms. The results indicated that, with the exception of semantic dementia, action naming was more impaired than object naming in all patient groups. The discrepancy was similar in frontal variant of FTD and Alzheimer's disease patients, whereas patients with nonfluent primary progressive aphasia, PSP, and CBD were significantly more impaired in the oral production of actions than of objects. These findings indicate that action naming impairment is not a general feature of FTD, but rather is associated with conditions that affect the frontoparietal-subcortical circuits involved in action knowledge and action representation.

Aged↗
PubMed2005

Effects of estrogens on cognition and brain morphology: involvement of the cerebellum.

OBJECTIVES: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Among studies reporting a positive effect of estrogen replacement therapy (ERT) on cognition, the most consistent evidence is that it enhances verbal memory and visuospatial functions. In the present study we investigated the effect of ERT on cognition and on brain morphology in healthy postmenopausal women, taking into account the distinction in current and past ERT users. METHODS: Participants were postmenopausal nondemented women recruited from the community: ERT users were 40 (23 current users, 17 past users), while never users were 43. Forty of recruited subjects gave consent to undergo 3D high resolution MRI (16 current users, 7 past users and 17 never users). Participants underwent MMSE and a battery of neuropsychological tests measuring memory, language, intelligence, attention and visuo-spatial abilities. RESULTS: The past users group outperformed the never users in four tests: Token test, WCST categories, attentional matrices and Rey's delayed list; the current users group outperformed the never users in the Rey's list test. ERT users had greater grey matter volumes mainly in the cerebellum, but an increase was observed also in the parietal and occipital cortex. CONCLUSIONS: ERT use appears to improve linguistic, attentive and planning abilities. Interestingly, the beneficial effects on cognition were detected mainly in the past users subgroup. Here we propose that the trophic effect of estrogens on cerebellum might account for the observed improvement in cognition.

Case-Control Studies↗
PubMed2004

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Adolescent↗
PubMed2004

Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia.

Genetic factors are involved in the aetiology of dementias. Three genes have been identified which, when mutated, cause Familial Alzheimer disease (FAD): the presenilin-1 (PS1), the presenilin-2 (PS2) and the amyloid precursor protein (APP) genes. Together, these mutations are responsible for 30-50% of the cases with autosomal dominant Alzheimer disease (AD), and for about 5% of all AD cases. While over 130 mutations have been identified in PS1, mutations in PS2 and APP are rarer, since only 10 and 22 mutations, respectively, have been found in these FAD genes. Instead, mutations in the MAPT gene were associated with Familial Frontotemporal dementia (FFTD) linked to chromosome 17 (FTDP-17). Frontotemporal dementia (FTD) can occur in a sporadic form, but in 30-50% of cases there is a positive family history of dementia. In this study, we determined the spectrum of mutations and the relative contribution of the above mentioned four genes in our Italian clinical series of patients with a positive family history of dementia.

Aged↗
PubMed2003

Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2.

Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-beta, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects. LOAD was associated with homozygous C/C PLAU genotype in the whole sample (chi2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE epsilon4 carrier status (chi2> or = 6.84, P< or =0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2.61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.

Age of Onset↗
PubMed2003

Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene.

Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.

Alzheimer Disease↗
PubMed2003

BACE-2 is overexpressed in Down's syndrome.

Brain deposition of the amyloid-beta protein (Abeta) is a frequent complication of Down's syndrome (DS) patients. Abeta peptide is generated by endoproteolytic processing of Abeta precursor protein by gamma and beta secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the beta-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Abeta precursor protein at its beta site and more efficiently at a different site within Abeta. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.

Adult↗
PubMed2003

An electronic memory aid to support prospective memory in patients in the early stages of Alzheimer's disease: a pilot study.

The use of an electronic memory aid (EMA) for patients with mild-to-moderate probable Alzheimer disease is examined in five outpatients aged 58-79 years. The ability to remember to carry out seven tasks at a particular time was evaluated in three experimental conditions: recall without an external memory aid, recall with a written list and recall with support available from an EMA. The use of an EMA significantly improved patients' prospective memory, while the written list and free recall were not useful. Future research that examines the value of using an EMA to help with tasks that are associated with prospective memory with a larger sample of patients within their own home context is suggested.

Age Factors↗
PubMed2002

A transcultural study of agitation in dementia.

Agitation is one of the most troublesome behaviors in demented patients. It is etiologically heterogeneous and has varied associated behaviors. To explore the transcultural differences in the manifestation of agitation, we evaluated 50 consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy, and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE). In a focused analysis, only patients with composite NPI scores > 2 for agitation were selected, with similar levels of disease severity as measured by the MMSE, from the three groups (n = 15 per group) to evaluate culturally specific correlates of agitation. Agitated Taiwanese had significantly more hallucinations than either Italian or American patients. Agitated Italian patients had significantly more apathy than both Taiwanese and American patients. Cultural factors may influence the manifestation of agitation more than a common underlying neuropathology. Management strategies targeting unique behavioral instigators of agitation may be specific for different ethnic groups.

Aged↗
PubMed2001

Detection of the presenilin 1 COOH-terminal fragment in the extracellular compartment: a release enhanced by apoptosis.

Mutations in gene encoding presenilin 1 (PS1) are responsible for the majority of familial Alzheimer's disease (FAD) cases. We studied PS1 localization in HEK293 cells and in primary neurons obtained from rat cortex and hippocampus. We first demonstrated that PS1-CTF, but neither PS1-FL nor PS1-NTF, is released into the medium as a soluble and membrane-associated form. After induction of apoptosis with staurosporine (Sts), we observed a dramatic increase in the level of PS1-CTF in the medium, both in HEK293 and in primary neurons. Immunocytochemical analysis suggested that the release of PS1-CTF might occur via membrane shedding. Abeta(1-42) treatment reduced PS1-CTF extracellular levels. This decrease was strongly associated to an impaired secretion of sAPP fragments, thus suggesting a role of PS1-CTF in the control of trafficking and generation of APP fragments.

Alzheimer Disease↗
PubMed2001

Non-replication of association between cathepsin D genotype and late onset Alzheimer disease.

In two recent studies from Germany, a strong association was found between the allelic variant T of the amino acid substitution encoding polymorphism 224 C/T (A38V) in exon 2 of the cathepsin D gene (CTSD) and late onset Alzheimer disease (AD). Other studies from Europe and the USA revealed ambiguous results. Therefore, we performed an independent association study on CTSD and AD in a sample of 324 Caucasian patients from Germany, Switzerland, and Italy with late onset AD, and 302 non-demented controls. We could not confirm an association between CTSD genotype and AD, although there was a slight but not significant increase in frequency of the T allele and T carrier status in AD. Post hoc data analyses suggested that there might be a stronger effect of CTSD genotype on AD risk in males, and an interaction between CTSD and APOE genotypes in males but not females.

Age Factors↗
PubMed2001

A brief neuropsychological assessment for the differential diagnosis between frontotemporal dementia and Alzheimer's disease.

The neuropsychological performance (including measures of language, semantic memory, visual and spatial perception and executive functions) of a group of 14 patients with the clinical diagnosis of probable frontotemporal dementia was compared with that of a group of 14 patients with a clinical diagnosis of probable Alzheimer's disease. The aim was to identify a specific cognitive profile of frontotemporal dementia, which could be used to select a sensitive, short evaluation for the differential diagnosis with Alzheimer's disease. Both groups were severely impaired in most tasks, including those 'frontal lobe' tests which have been suggested to play an important role in differential diagnosis. Significant differences were found only for a minority of tests (oral praxis, visual-spatial perception, and verbal fluency). A logistic regression showed that a shortened testing procedure based on four tests (Rey-Osterreith complex figure test recall, phonemic fluency, oral apraxia, and cube analysis) achieved a 70% sensitivity and 80% specificity for the correct classification of patients in the frontotemporal dementia or Alzheimer's disease group. In conclusion, a brief neuropsychological evaluation including these four tests, as well as other measures sensitive to the frontal impairment, can be useful in the differential diagnosis between the two pathologies, along with the clinical data.

Aged↗
PubMed2000

Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.

In a family with autopsy-confirmed Alzheimer disease, the authors found a mutation in the presenilin 2 (PS2) gene (PSEN2) that predicts a methionine-to-isoleucine change at PS2 residue 239 (M239I), at which a change to valine was known in another family. Phenotypic expression of M239I was highly variable, with disease onset between age 44 and 58 years, and two nonaffected mutation carriers at age 58 and 68 years. The data showed no influence of APOE but were compatible with other possible genetic modifiers of the phenotype or penetrance of M239I.

Adult↗