How the cognitive reserve interacts with β-amyloid deposition in mitigating FDG metabolism: An observational study

This observational study had the aim to assess the interaction between cognitive reserve (CR) and cerebrospinal fluid β-amyloid1-42 (Aβ1-42) in modulating brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism in patients with moderate Alzheimer disease (AD).Twenty-seven patients with probable AD and 25 neurological normal subjects (NNS) entered the study. All participants had an FDG-PET scan, and AD patients also received a lumbar puncture to measure Aβ1-42, 181p-tau, and Tau concentrations. Based on years of formal education, AD patients were classified as highly educated-AD (years of formal education >5) or less educated-AD (years of formal education <5). By using a voxel-wise approach, we first investigated differences in the cerebral glucose uptake between AD and NNS, then we assessed the interaction between level of education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET metabolism in the patient groups.Significantly lower glucose uptake was observed in the posterior cingulate gyrus, in the precuneus, in the inferior and medial temporal gyrus, and in the inferior parietal lobule of AD patients compared with NNS. A significant interaction was found between CR and Aβ1-42 values on brain metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients with higher CR level and marked signs of neuropathology showed glucose hypometabolism in regions typically targeted by AD pathology. This finding supports the hypothesis that CR partially compensates for the effect of Aβ plaques on cognitive impairment, helps in patients' clinical staging, and opens new possibilities for the development of nonpharmacological interventions

The need for harmonization and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group

Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status. Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a “big data” common data set. We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe. A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries

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Abstract: In order to provide a safe and separate system on which to train, test, and teac

On the role of a coumarin derivative for sensing applications: Nucleotide identification using a micellar system

The recognition of nucleotides is of crucial importance because they are the basic constituents of nucleic acids. The present study is focused on the selective interaction between a novel amphiphilic fluorophore containing coumarin and imidazole, CI (1-methyl-3-(12-((2-oxo-2H-chromen-7-yl)oxy)dodecyl)-1H-imi dazol-3-ium bromide), and different nucleotide-monophosphates (NMPs). It was supposed that the solubilization of the low water soluble CI in a micelle system of hexadecyltrimethylammonium chloride (CTAC) would make the coumarin moiety of CI available to the interaction with the water-soluble NMPs. Changes in CTAC critical micelle concentration suggested that CI strongly interacted with the host cationic surfactant, thus forming a positively charged interface enriched with coumarin able to interact with the anionic NMPs. Steady-state fluorescence quenching revealed that CI/CTAC system was capable of distinguish between purine- and pyrimidine-based nucleotides. A modified Stern-Volmer equation permitted the use of a quenching model that accounted for the possible interactions between the micelles and the nucleotides. The data analysis allowed calculating selective parameters that differentiated according to the type of nucleotide either at 25 or 50 °C. Our results established the utility of the novel coumarin derivative fluorophore, supported by the simple and suitable micellar systems, as a tool for DNA sensing applications

Effects of monoolein-based cubosome formulations on lipid droplets and mitochondria of HeLa cells

Despite the remarkable development of nanoparticles for different purposes, relatively little is known about their interaction with biological systems and individual cells. Here the effects of two monooleinbased cubosome formulations stabilized by Pluronic F108 and F127 were investigated against HeLa cells. Microscopy analysis on living cells loaded with organelle-specific fluorescent probes was performed to assess the formation of cytoplasmic lipid droplets after nanoparticle treatment. Mitochondrial membrane potential and mitochondrial ROS generation were also investigated in relation to the capability of the accumulated lipids to affect mitochondrial functions. Values of the main cellular unsaturated fatty acids were also measured to assess cell lipid profile modulation. Results from this study show that the uptake of both cubosome formulations induced modification of the cell lipid profile, lipid droplet accumulation, mitochondrial hyperpolarization and mitochondrial ROS generation. These results shed some light on the influence exerted by monoolein-based cubosome formulations on subcellular organelles and their possible adverse effects on cell functions

A new family of bis-ureidic receptors for pyrophosphate optical sensing

A new family of bis-ureidic receptors (L11–L66) has been synthesised. The binding properties of L11–L66 towards different anions (acetate, benzoate, glutarate, malonate, dihydrogen phosphate, hydrogen pyrophosphate, triphosphate, AMP and ADP) have been studied by means of 1H-NMR, UV-Vis and fluorescence spectroscopies and a remarkable affinity for HPpi3? has been observed in the case L33 (in DMSO-d6 and DMSO-d6–5% H2O) which also acts as a fluorimetric chemosensor, even to the naked eye, for this anion. Theoretical calculations helped us explain the binding properties observed