Patterns of brain atrophy in dysexecutive amnestic mild cognitive impairment raise confidence about prodromal AD dementia

Background: Prediction models aimed at detecting risk of progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) dementia increase their accuracy when impaired executive functions enter the analysis. This suggests that impaired executive functions in MCI are likely linked to the prodromal stages of AD dementia. Neuroimaging assessment of such patients would allow exploring if they show AD related patterns of brain atrophy. We hypothesized that AD sensitive brain regions would show discrimination between dysexecutive amnestic MCI (maMIC) and healthy controls. Method: We analysed 32 healthy controls and 23 MCI patients. Patients were divided in single domain amnestic MCI, multidomain amnestic MCI (i.e., with the dysexecutive component), and non-amnestic MCI. Brain volume data entered regression models to analyse which brain regions predict group membership (control vs maMCI). Stepwise lineal regression model was then conducted to identify the brain regions with better prediction power. Results: Four variables were able to predict group membership in simple lineal regression models: entorhinal cortex, lingual gyrus and parahippocampal gyrus in the left hemisphere and fusiform gyrus in the right hemisphere. The entorhinal cortex provided the most accurate model (F(1, 42) = 14.19, p=0.001, R2=0.24). Linear regression models were run with performance on executive function tasks including tests of switching, planning, verbal fluency and working memory. The most accurate model returned Letters and Numbers and categories fluency (F(2, 44) = 21.35, p=0.000, R2=0.48) suggesting that working memory and category generation are the functions contributing to the dysexecutive profiles observed in maMCI patients. Conclusion: Dysexecutive profiles in multidomain amnestic MCI together with neuroimaging volumetric analysis increase the probability of identifying the prodromal stages of AD dementia

Impact of intrathecal cell therapy with autologous stromal cells on short-term memory binding in early Alzheimer's disease : one-year follow-up assessment of two cases

Background: We had previously reported that the administration of autologous stromal cells (ASCs) therapy to two patients with mild AD dementia led to a global increase in cerebral glucose metabolism which was accompanied by significant improvement of visual short-term memory binding (VSTMB), a function known to be a marker of AD. We suggested that intrathecal administration of autologous ASCs could be considered a new therapeutic strategy for AD dementia (Vaquero et al., 2019). We were interested in investigating the post-intervention durability of such cognitive improvements. Methods: We studied two AD patients with cerebral beta-amyloid neuritic plaques detected with 18FFDG-PET. The patients received every three months 100 million of ASCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F-FDG-PET and assessment with the visual short-term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Here we report on the assessment of these patients one year after the therapy. We compared them with 4 AD patients who did no undergo stem cell therapy. Results: Single case statistics revealed that benefits drawn by treated patients from the therapy remained a year after. Using a more taxing version of the VSTMB test (memory load of 3 items) we observed that, after the therapy, the chance that an untreated AD patient would show more impairment was 75.45% (p= 0.24) for Case 1 and 89.23% (p=0.11) for case 2. This chance remained after 1 year post-treatment for Case 1 (75.45%, p=0.24) and increased for Case 2 (96.89%, p=0.031). Conclusion: Improvements of memory functions known to be marker for AD in patients who underwent stem cell therapy remained stable after one year post-intervention. This offers a new therapeutic strategy for AD

Qualitative Assessment of Effective Gamification Design Processes Using Motivators to Identify Game Mechanics

This research focuses on the study and qualitative assessment of the relationships between motivators and game mechanics per the ratings of expert gamification consultants. By taking this approach, it is intended that during the design phase of a gamified system, decisions can be made about the design of the system based on the motivators of each of the profiles. These motivators can be determined from the information provided by the potential players themselves. The research presented starts from a previous analysis in which, based on the three most used gamification frameworks and through a card sorting technique that allows the user to organize and classify the content, a set of mechanics are determined. In the present study, each of the mechanics is analyzed, and a more precise motive is decided. As a result, a higher level of personalization is achieved and, consequently, approximates a higher level of gamification effectiveness. The main conclusions are implemented in the development of the Game4City 3.0 project, which addresses gamified and interactive strategies to visualize urban environments in 3D at an educational and social level

Refining memory assessment of elderly people with cognitive impairment:Insights from the short-term memory binding test

Alzheimer’s disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). We compared data from two studies on temporary binding which assessed people with MCI and controls using different memory loads (2 or 3 items). Selective binding impairments were found in MCI, but relative to controls, such selectivity was contingent upon memory load (i.e., present with 2 items). Further analysis with MCI people who tested positive to neuroimaging biomarkers (i.e., hippocampal atrophy) confirmed that this specific binding impairments are a feature of prodromal AD. The temporary binding task has been recently suggested by consensus papers as a potential screening tool for AD. The results presented here inform on task properties that can maximise the reliability of this new assessment tool for the detection of memory impairments in prodromal cases of AD

Variational Mean Field approach to the Double Exchange Model

It has been recently shown that the double exchange Hamiltonian, with weak antiferromagnetic interactions, has a richer variety of first and second order transitions than previously anticipated, and that such transitions are consistent with the magnetic properties of manganites. Here we present a thorough discussion of the variational Mean Field approach that leads to the these results. We also show that the effect of the Berry phase turns out to be crucial to produce first order Paramagnetic-Ferromagnetic transitions near half filling with transition temperatures compatible with the experimental situation. The computation relies on two crucial facts: the use of a Mean Field ansatz that retains the complexity of a system of electrons with off-diagonal disorder, not fully taken into account by the Mean Field techniques, and the small but significant antiferromagnetic superexchange interaction between the localized spins.Comment: 13 pages, 11 postscript figures, revte

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer's Disease

BACKGROUND: Apathy is a complex multidimensional syndrome frequently reported in Alzheimer's disease (AD) and is associated with impaired awareness. Here we present a psychometrically robust method to profile apathy in AD.  OBJECTIVES: To determine the validity and reliability of a multidimensional apathy measure, the Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its associations in AD.  METHODS: 102 people with AD and 55 healthy controls were recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES), Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of Daily Living (LIADL). Psychometric properties of the DAS were determined. AD-Control comparison was performed to explore group differences on the DAS. Latent Class Analysis (LCA) was used to explore the profile of apathy in AD.  RESULTS: The DAS had a good to excellent Cronbach's standardized alpha (self-rated = 0.85, informant/carer-rated = 0.93) and good convergent and divergent validity against standard apathy (AES) and depression (GDS-15) measures. Group comparison showed people with AD were significantly higher for all apathy subtypes than controls (p < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4% in the Global apathy, and 29.4% in the Minimal apathy group.  CONCLUSIONS: The DAS is a psychometrically robust method of assessing multidimensional apathy in AD. The apathy profiles in AD are heterogeneous, with additional specific impairments relating to awareness dependent on apathy subtype

Viroporins

Viroporins are a group of proteins that participate in several viral functions, including the promotion of release of viral particles from cells. These proteins also affect cellular functions, including the cell vesicle system, glycoprotein trafficking and membrane permeability. Viroporins are not essential for the replication of viruses, but their presence enhances virus growth. Comprising some 60-120 amino acids, viroporins have a hydrophobic transmembrane domain that interacts with and expands the lipid bilayer. Some viroporins also contain other motifs, such as basic amino acid residues or a domain rich in aromatic amino acids that confers on the protein the ability to interact with the interfacial lipid bilayer. Viroporin oligomerization gives rise to hydrophilic pores at the membranes of virus-infected cells. As the list of known viroporins steadily grows, recent research efforts focus on deciphering the actions of the viroporins poliovirus 2B, alphavirus 6K, HIV-1 Vpu and influenza virus M2. All these proteins can enhance the passage of ions and small molecules through membranes depending on their concentration gradient. Future work will lengthen the list of viroporins and will provide a deeper understanding of their mechanisms of action.This work was supported by the Comunidad Autonoma de Madrid (082‐0024/2000), Instituto de Salud Carlos III (01/0042) and the DGICYT (PM99‐0002). The authors also acknowledge the institutional grant awarded to the Centro de Biologı́a Molecular ‘Severo Ochoa’ by the Fundación Ramón Areces.S

Nature-inspired calcium phosphate coatings : present status and novel advances in the science of mimicry

There has been a growing awareness in materials science that the adaptation of nature biological processes can lead to significant progresses in the controlled fabrication of advanced materials for an all range of applications. To learn from, understand and apply these natural processes for producing calcium phosphate coatings that are biologically similar to bone apatite, mimicking its properties, has driven the attention of many researchers in recent years. This article reviews the most relevant advances in this emerging research field, pointing out several approaches being introduced and explored by distinct laboratories

Overview of the techniques used for the study of non-terrestrial bodies: Proposition of novel non-destructive methodology

Meteorites and impact glasses have been largely analysed using different techniques, but most studies have been focused on their geologicalemineralogical characterization and isotopic ratios, mainly of a destructive nature. However, much more information can be gained by applying novel non-destructive analytical procedures and techniques that have been scarcely used to analyse these materials. This overview presents some new methodologies to study these materials and compares these new approaches with the commonly used ones. Techniques such as X-Ray Fluorescence (XRF) and Laser Induced Breakdown Spectroscopy (LIBS), for elemental characterization, the hyphenated Raman spectroscopy- SEM/EDS and the combination of them, allow extracting simultaneous information from elemental, molecular and structural data of the studied sample; furthermore, the spectroscopic image capabilities of such techniques allow a better understanding of the mineralogical distribution. © 2017 Elsevier B.V. All rights reserved.Ministerio de Economía, Industria y Competitividad (project ESP2014-56138-C3-2-R