Parkinson's Disease-Mild Cognitive Impairment (PD-MCI): A Useful Summary of Update Knowledge

Mild cognitive impairment (MCI) is a common feature in Parkinson's Disease (PD), even at the time of diagnosis. Some levels of heterogeneity in nature and severity of cognitive impairment and risk of conversion to Parkinson's Disease Dementia (PDD) exist. This brief overview summarized the current understanding of MCI in PD, by considering the following major points: historical development of the clinical entity, evaluation, epidemiology, predictors and outcomes, neuroimaging findings, pathophysiology, treatment, and pharmacological and non-pharmacological intervention. MCI in PD represents a concept in evolution and plays a pivotal role in advancing our understanding of the disease mechanisms, with the ultimate goal of building effective strategies to prevent conversion into PDD. Challenges for future research are also discussed

COGNITIVE PSYCHOPATHOLOGY IN SCHIZOPHRENIA: COMPARING MEMORY PERFORMANCES WITH OBSESSIVE-COMPULSIVE DISORDER PATIENTS AND NORMAL SUBJECTS ON THE WECHSLER MEMORY SCALE-IV

Background: Memory system turns out to be one of the cognitive domains most severely impaired in schizophrenia. Within the theoretical framework of cognitive psychopathology, we compared the performance of schizophrenia patients on the Wechsler Memory Scale-IV with that in matched patients with Obsessive-compulsive disorder and that in healthy control subjects to establish the specific nature of memory deficits in schizophrenia. Subjects and methods: 30 schizophrenia patients, 30 obsessive-compulsive disorder patients and 40 healthy controls completed the Wechsler Memory Scale-IV. Schizophrenia symptom severity was assessed by the Positive and Negative Syndrome Scale (PANSS). Performances on memory battery including Indexes and subtests scores were compared by a One-Way ANOVA (Scheffé post-hoc test). Spearman Rank correlations were performed between scores on PANSS subscales and symptoms and WMS-IV Indexes and subtests, respectively. Results: Schizophrenia patients showed a memory profile characterized by mild difficulties in auditory memory and visual working memory and poor functioning of visual, immediate and delayed memory. As expected, schizophrenia patients scored lower than healthy controls on all WMS-IV measures. With regard to the WMS-IV Indexes, schizophrenia patients performed worse on Auditory Memory, Visual Memory, Immediate and Delayed Memory than Obsessive-compulsive disorder patients but not on Visual Working Memory. Such a pattern was made even clearer for specific tasks such as immediate and delayed recall and spatial recall and memory for visual details, as revealed by the lowest scores on Logical Memory (immediate and delayed conditions) and Designs (immediate condition) subtests, respectively. Significant negative correlations between Logical Memory I and II were found with PANSS Excitement symptom as well as between DE I and PANSS Tension symptom. Significant positive correlations between LM II and PANSS Blunted affect and Poor rapport symptoms as well as DE I and PANSS Blunted affect and Mannerism and Posturing symptoms, were found too. Conclusions: Memory damage observed in schizophrenia patients was more severe and wider than that of patients with obsessive-compulsive disorder, except for visual working memory. Memory dysfunction, mainly related to episodic memory damage and reduced efficiency of central executive, is intimately connected to the specific psychopathological processes characterizing schizophrenia. Implications for therapeutics and cognitive remediation techniques are discussed

Effects of nanomaterials on biological barriers, fetal and post-natal, and evaluation of epigenetic toxicity

Beyond the opportunities offered by nanotechnology research, there is a great need of studies aimed at understanding the harmful effects of general exposure to nanomaterials. My Ph.D. project aimed to be part of this evaluation, focusing on the interaction and the induction of possible toxic effects of two fibrous nanomaterials (asbestos and carbon nanotubes) at two critical internal biological barriers: the pleura and the placenta. The work is carried out by using advanced microscopy (\ub5XRM and XRF) based on synchrotron radiation and other microscopes (SEM and AFM), and also conventional molecular analysis (PCR and Sanger sequencing) and advanced spectroscopic measurements (UV-Raman). We conducted biochemical studies by using the advanced X-Ray microscopy and fluorescence (\ub5XRM and XRF) techniques in order to reveal mechanisms of toxicity in human mesothelial (MeT5A) and placental cell lines (BeWo) exposed to carbon nanotubes (raw-SWCNT, purified- and highly purified-SCWCNT) or asbestos (crocidolite fibres). Other microscopes (AFM, atomic force microscopy and SEM, Scanning Electron Microscope) are added in some experiments, to better investigate the morphology and the cell-nanofiber interactions. The results obtained with the combination of microscopic techniques allowed to reveal similar as well as different toxic mechanisms in the two internal barriers. The cells treated with raw-SWCNT and crocidolite fibres compared to the control showed an severe alteration of iron metabolism, which is maximal in the pleural cells and is clearly related to the presence of iron into the fibre. X-ray microscopy images (absorption and phase contrast imaging) confirm that the toxicity of nanomaterials is characterized by membrane damage with vesicle secretion and filipodia formation. In relation to this toxic mechanism quite complex and still unknown we evaluated the presence of intracellular ferritin in treated cells. The results demonstrated that crocidolite and \u201craw\u201d carbon nanotubes increase the amount of intracellular ferritin in both cell models, while purified and highly purified carbon nanotubes give values comparable to control. The stimulation is clearly lower in placental cells, clearly linked to a different or lower uptake of fibres in these cells, suggesting that this barrier is less vulnerable than the pleura. We also investigated the genetic effects and genetic predisposition to toxicity of nanomaterials (nanotoxicogenomic). Since we have to learn from asbestos, one study investigates the possible genetic predisposition to develop mesothelioma after asbestos exposure by looking for BAP1 gene mutations in 30 cases of mesothdelioma. Sanger sequencing of BAP1 gene in the 30 patients identified one non-synonymous variant and two intronic variants. While Sanger sequencing of cDNA revealed no alternative splicing due to the nucleotide change for each mutations. In silico mutation analysis was performed in a predicted protein structure of BAP1 protein without any significant possible effect of the amino acid change about exonic mutations of patient 9. Finally, MLPA (Multiplex ligation-dependent probe amplification) analysis revealed no significant copy number variations at exonic level in all samples. The last aim of molecular studies was to test the feasibility of UV-Raman (IUVS beamline, Elettra Synchrotron of Trieste) spectroscopy to reveal epigenetic changes at DNA level after nanomaterial exposure. An oxidative environment has been created in vitro by using carbon nanotubes (raw-SWCNT), which contain some impurity in metal traces (iron), and free radicals OH\u2022 (derived from H2O2). In this condition the nucleotides (dATP, dCTP, dGTP and dTTP) result in increased susceptibility to oxidative damage. The results demonstrated that UV-Raman spectroscopy is useful to reveal the chemical changes that affect the nitrogenous bases after nanomaterials exposure, providing a \u201cfingerprint\u201d of the oxidative DNA damage

La didattica della matematica nei Laboratori del Corso di specializzazione al sostegno per gli insegnanti della secondaria

The quality of education depends on teacher’s choices in order to ameliorateteaching-learning process. Whit regard to it, laboratory didactics is theprimary methodology able to direct knowledge cores addressed throughpractical and realistic tasks by concrete illustrations and vivid images. Theexperience of Maths didactics in the post-graduate Course for supportteachers of secondary school provided participants the awareness of labpotential, as a critical ability upon their planning, action, evaluation andmonitoring, by giving effect the ability to project and the culture of trainingduring work.La qualità dell’istruzione dipende dalle scelte che il docente pone in essere,allo scopo di migliorare il processo di insegnamento-apprendimentorispetto a cui la didattica laboratoriale si colloca come metodologia elettivain grado di convogliare, attraverso illustrazioni concrete ed immagini vividee suggestive, i nuclei dei saperi, che vengono affrontati mediante compitipratici orientati al reale. L’esperienza della didattica della matematica, alCorso di specializzazione per il sostegno agli alunni con disabilità della secondaria,ha prodotto la consapevolezza nei partecipanti delle potenzialitàespresse dal laboratorio come capacità critica sul proprio processo di pianificazione,azione, valutazione e monitoraggio messo in atto, rendendo efficacila capacità progettuale e la cultura della formazione in servizio

Mild Cognitive Impairment: Neuropsychological Profile

Dementia is a highly debilitating disease that is growing in the world because of the progressive aging of the population. Dementia affects more than 25 million people in the world, with around 5 million new cases occurring every year (Brookmeyer et al., 2007). It has been estimated that 26% of women and 21% of men over 85 years of age suffer from several types of dementia, of which approximately 70% are of Alzheimer’s type (Qui et al., 2009). The prevalence of dementia worldwide was estimated to be 3.9 in the elderly population over 65 years of age (Ferri et al., 2005). The pooled data of population-based studies in Europe suggests that the prevalence of Alzheimer’s Disease (AD) in people over 65 years of age is 6.4% (Lobo et al., 2000) for dementia and 4.4% while the pooled incidence rate for AD is 19.4 per 1000 person-years (Fratiglioni et al., 2000). Dementia currently represents a social and health emergency because of clinical features of the disease (progressive disability, severe cognitive impairment, and behavioural disturbances), economic implications (impact on the Welfare State), and human costs of patients and caregivers. Thus, the boundary state between normal aging and early insanity is an area of research interest for both clinical-diagnostic and therapeutic-rehabilitative reasons. Literature presents many attempts to classify slight cognitive impairment in order to distinguish between physiological and pathological aging. The concept of slight cognitive impairment in aging appears confused with dementia until Kral (1962), who described senescent forgetfulness by distinguishing a physiological cognitive decline due to aging (“Benign Senescent Forgetfulness”) from a pathological cognitive decline (“Malignant Senescent Forgetfulness” or “Amnestic Syndrome”) apt to convert into dementia. After Kral, several studies provided different classifications of slight cognitive impairment but they did not completely describe its clinical features. In 1995, Petersen et al. defined the primary diagnostic criteria for Mild Cognitive Impairment (MCI) that were subsequently reviewed (Petersen et al., 1999). In order to specify MCI subtypes, Petersen (2004) proposed a new classification model. Mild Cognitive Impairment refers to the clinical condition in which individuals show a slight cognitive impairment not severe enough to satisfy dementia diagnostic criteria but greater than expected for age and schooling, without notable interference in daily life activities. It represents the most valuable nosological entity currently adopted by clinicians to diagnose a specific form of slight cognitive impairment, believed to be a high-risk condition for developing dementia (especially Alzheimer’s Disease) (AD). However, researchers have severely criticized MCI for its marked inaccuracy for both theoretical and clinical reasons (Chertkow et al., 2008). Clinical research did not completely describe the neuropsychological features of MCI and its subtypes, and it did not provide characteristic markers to predict dementia, except those related to memory decline (Perri et al., 2005; 2007). Starting from this assumption, the research project aims at: 1. describing the historical and conceptual course of mild cognitive impairment and its associated clinical entities; 2. critically analyzing psychodiagnostic procedures and psychometric rules commonly used for diagnosis; 3. pointing out the potential role of cognitive Activation Therapy (AT) for MCI subjects in delaying dementia onset; 4. estimating the proportion and defining the different neuropsychological profiles of each MCI subtype; 5. investigating the possibility to find neuropsychological markers apt to predict dementia

Pretreatment with Ibuprofen Augments Circulating Tumor Necrosis Factor-α, Interleukin-6, and Elastase during Acute Endotoxinemia

Plasma levels of tumor necrosis factor-α (TNFα), interleukin-1 (IL-1),and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNFα concentrations with maximal levelsat 90 min (369 ± 44 pg/ml, P < .001 vs. saline controls, n = 7). The rise in TNF-α was followed by a rise in plasma IL-6 (27 ± 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNFα levels(627 ± 136 pg/ml) at 120 min and IL-6 peaks (113 ± 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNFα was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenaseinhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulatio

CONSCIOUS ATTENTION DEFECT AND INHIBITORY CONTROL DEFICIT IN PARKINSON’S DISEASE-MILD COGNITIVE IMPAIRMENT: A COMPARISON STUDY WITH AMNESTIC MILD COGNITIVE IMPAIRMENT MULTIPLE DOMAIN

Background: Frontal/executive dysfunction commonly occurs in Parkinson\u27s disease - Mild Cognitive Impairment (PD-MCI patients). However, to date, the number of studies comparing PD-MCI and MCI patients of other etiologies are too small. The present study aims at clarifying the attention/working memory and executive dysfunction of PD-MCI patients in comparison to amnestic MCI multiple domain patients with first extended then abbreviated structural brain changes suggesting preclinical Alzheimer’s Disease. Subjects and methods: 40 PD-MCI patients and 40 amnestic MCI multiple domain (aMCI+) patients were diagnosed according to the International guidelines. 22 healthy subjects were also recruited as control group. The groups were assessed by a wide neuropsychological battery, including measures of attention/working memory (Digit Span and Stroop Test), executive functions (Tower of London-Drexel Version -TOLDX- and Brixton Test), language (Boston Naming Test and Category Fluency), memory (Prose Recall and Pairs Associates Learning), and visuospatial function (Street\u27s Completion Test and Constructive Apraxia Test). Performances were compared by non parametric tests. Spearman correlations were performed to explore association between neuropsychological measures of attention/working memory and executive functions in PD-MCI group. Results: The PD-MCI patients performed worse on Digit Span and Stroop Interference/Error than aMCI+ and controls. AMCI+ patients, in turn, showed a greater deficit on TOLDX Initiation Time and on Violation Time than PD-MCI and controls. Both PDMCI and aMCI+ patients reported lower scores on Stroop Interference/Time than controls. Moreover, aMCI+ patients performed worse then controls on Brixton Test. Positive correlations between Digit Span and Stroop Interference/Error, Stroop Interference/Error and TOLDX Execution Time, Total Time and Violation Time, Stroop Interference Time and TOLDX Move Score and Total Time were found in PD-MCI group. Conclusion: PD-MCI patients mainly present a conscious attention defect and an inhibitory control deficit than aMCI+. PDMCI patients with deficits in attention/working memory domain should undergo specific cognitive trainings in order to improve cognitive abilities and prevent Parkinson\u27s Disease Dementia onset

Effects of Mediterranean diet and weight loss on blood-lipid profile in overweight adults with hypercholesterolemia

Blood cholesterol has been positively associated with increased cardiovascular risk as a modifiable risk factors together with the lifestyle and diet. Furthermore, an improvement of the blood-lipid profile seems to be able to produce a decrease in cardiovascular events. Cholesterol plasma levels are related to the body mass index (BMI) and are affected by diet. The aim of this study was to evaluate the effectiveness of a Mediterranean diet (MD) weight-loss programme to improve blood cholesterol profiles in overweight adults subjected to real-world outpatient diet. Forty-nine hypercholesteraemic, overweight adults of both sexes were subjected to a dietary weight-loss intervention. Patients were prescribed a slightly hypocaloric MD for 16 weeks, followed by an 8-week follow-up period with a normocaloric diet. Data showed significant weight loss and cholesterol blood profile improvement both under the hypocaloric diet and during the follow-up period. In particular, the decrease in both Total and LDL-cholesterol was greater than their critical differences indicating the clinical relevance of blood lipid improvement induced by MD