Spontaneous Speech and Emotional Response modeling based on One-class classifier oriented to Alzheimer Disease diagnosis

The purpose of our project is to contribute to earlier diagnosis of AD and better estimates of its severity by using automatic analysis performed through new biomarkers extracted from non-invasive intelligent methods. The methods selected in this case are speech biomarkers oriented to Sponta-neous Speech and Emotional Response Analysis. Thus the main goal of the present work is feature search in Spontaneous Speech oriented to pre-clinical evaluation for the definition of test for AD diagnosis by One-class classifier. One-class classifi-cation problem differs from multi-class classifier in one essen-tial aspect. In one-class classification it is assumed that only information of one of the classes, the target class, is available. In this work we explore the problem of imbalanced datasets that is particularly crucial in applications where the goal is to maximize recognition of the minority class as in medical diag-nosis. The use of information about outlier and Fractal Dimen-sion features improves the system performance.

Dendritic Spine Abnormalities in Hippocampal CA1 Pyramidal Neurons Underlying Memory Deficits in the SAMP8 Mouse Model of Alzheimer's Disease

SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer"s disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Projecte Android App

El projecte realitzat procura una aproximació real al desenvolupament amb dispositius Android. La funció principal de l'aplicació desenvolupada és consultar les dades meteorològiques utilitzant un web service i l'actual posició GPS.

Desenvolupament d'una app

El TFM ha consistit en participar i conèixer de prop tots el passos de desenvolupament d’una aplicació: elaboració d’un guió, realització de la part gràfica, programació i màrqueting. Per aquest motiu he realitzat unes hores de pràctiques a l'empresa Factoria Interactive SL. Durant aquest periòde vaig realitzar diversos guions per diferents apps relacionades amb continguts matemàtics i vaig participar en el programació de l'app "Dress up". I l'últim pas va consistir en penjar l'app a la botiga de Google Play. Per poder accedir a l'aplicació cal seguir el següent enllaç de Google Play: https://play.google.com/store/apps/details?id=eu.lafactoria.dressup&hl=es

Feature selection for automatic analysis of emotional response based on nonlinear speech modeling suitable for diagnosis of Alzheimer׳s disease

Alzheimer׳s disease (AD) is the most common type of dementia among the elderly. This work is part of a larger study that aims to identify novel technologies and biomarkers or features for the early detection of AD and its degree of severity. The diagnosis is made by analyzing several biomarkers and conducting a variety of tests (although only a post-mortem examination of the patients’ brain tissue is considered to provide definitive confirmation). Non-invasive intelligent diagnosis techniques would be a very valuable diagnostic aid. This paper concerns the Automatic Analysis of Emotional Response (AAER) in spontaneous speech based on classical and new emotional speech features: Emotional Temperature (ET) and fractal dimension (FD). This is a pre-clinical study aiming to validate tests and biomarkers for future diagnostic use. The method has the great advantage of being non-invasive, low cost, and without any side effects. The AAER shows very promising results for the definition of features useful in the early diagnosis of AD.

MemoryCon : Una aplicació d'Android per a potenciar la memòria dels malalts d'Alzheimer

This Degree Project is the development of an application for mobile devices with Android operating system. It is based on a generic manual with exercises for Alzheimer patients. The aim of the manual -and therefore, of the video game- is simply to be helpful in stimulating cognitive abilities of patients, ie players.

AltCApp : App per a la informació turística de l'Alt Camp

Projecte per al desenvolupament d'una aplicació per a dispositius Android, per al departament de turisme del Consell Comarcal de l'Alt Camp. Amb aquesta aplicació es vol proporcionar informació turística de la comarca. Amb aquest projecte també es vol desenvolupar un entorn web, per tal de poder accedir a la informació turística amb un navegador web, o des d'uns punts d'informació tàctils, dels que ja en disposa actualment el Consell Comarcal.

App para promoción de artistas y grupos musicales

La idea general inicial se basa en desarrollar una app para dispositivos Android que permita promocionar a artistas y grupos musicales. Lo que se pretende es crear una red socialespecializada tipo consumidor/productor donde los artistas o grupos podrán publicar su proyecto musical y los fans o usuarios en general podrán seguir la trayectoria de cualquier grupo o artista. En consecuencia, esta app contemplará dos tipos de usuarios: activos, los que generan contenido, y pasivos, que sólo consumirán servicios sin interactuar con el sistema.

A hybrid feature selection approach for the early diagnosis of Alzheimer's disease

Objective. Recently, significant advances have been made in the early diagnosis of Alzheimer’s disease from EEG. However, choosing suitable measures is a challenging task. Among other measures, frequency Relative Power and loss of complexity have been used with promising results. In the present study we investigate the early diagnosis of AD using synchrony measures and frequency Relative Power on EEG signals, examining the changes found in different frequency ranges. Approach. We first explore the use of a single feature for computing the classification rate, looking for the best frequency range. Then, we present a multiple feature classification system that outperforms all previous results using a feature selection strategy. These two approaches are tested in two different databases, one containing MCI and healthy subjects (patients age: 71.9 ± 10.2, healthy subjects age: 71.7 ± 8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6 ± 10.0; healthy subjects age: 69.4± 11.5). Main Results. Using a single feature to compute classification rates we achieve a performance of 78.33% for the MCI data set and of 97.56 % for Mild AD. Results are clearly improved using the multiple feature classification, where a classification rate of 95% is found for the MCI data set using 11 features, and 100% for the Mild AD data set using 4 features. Significance. The new features selection method described in this work may be a reliable tool that could help to design a realistic system that does not require prior knowledge of a patient's status. With that aim, we explore the standardization of features for MCI and Mild AD data sets with promising results.

Successful therapies for Alzheimer's disease: why so many in animal models and none in humans?

Peering into the field of Alzheimer's disease (AD), the outsider realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a deficit in translational research, i.e., to take a successful drug in mice and translate it to the patient. Efforts are still focused on novel projects to expand the therapeutic arsenal to 'cure mice.' Scientific reasons behind so many successful strategies are not obvious. This article aims to review the current approaches to combat AD and to open a debate on common mechanisms of cognitive enhancement and neuroprotection. In short, either the rodent models are not good and should be discontinued, or we should extract the most useful information from those models. An example of a question that may be debated for the advancement in AD therapy is: In addition to reducing amyloid and tau pathologies, would it be necessary to boost synaptic strength and cognition? The debate could provide clues to turn around the current negative output in generating effective drugs for patients. Furthermore, discovery of biomarkers in human body fluids, and a clear distinction between cognitive enhancers and disease modifying strategies, should be instrumental for advancing in anti-AD drug discovery.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.