Les maladies neurodégénératives (MND) comprennent principalement les maladies neuromusculaires, dont la sclérose latérale amyotrophique (SLA), les démences, dont la maladie d’Alzheimer, la maladie de Parkinson, la sclérose en plaques, la maladie de Huntington. Du fait de la multiplicité des facteurs à l’origine d’une perte pondérale, les MND sont à risque de dénutrition, ce qui peut altérer l’évolution de ces pathologies et la qualité de vie des patients. Le but de ce travail était d’étudier le statut nutritionnel et/ou l’effet de la prise en charge de patients atteints de SLA et de troubles cognitifs (démence vraie et/ou Mild Cognitive Impairment [MCI]) en France dans le cadre d’un réseau de santé, mais aussi en Afrique Centrale. Le réseau de santé Limousin Nutrition (LINUT) réalise des évaluations et interventions nutritionnelles au domicile de patients atteints de SLA et pour les résidents d’Etablissements d’Hébergement pour Personnes Agées Dépendantes (EHPAD). La première évaluation par le réseau des patients à domicile atteints de SLA retrouvait plus de troubles de la déglutition qu’en consultation spécialisée (60,0% vs 47,5%) ainsi que des troubles du goût (43,8%), non encore décrits lors de la SLA. Des améliorations de pratiques étaient proposées. Le réseau évaluait également des résidents en EHPAD, déments ou non déments, à la fois initialement et après un suivi d’environ 4 mois. La dénutrition touchait plus souvent les patients déments (56,1% vs 46,4% p=0,004), et les apports énergétiques de tous les résidents (26,4 ± 8,8 kcal/kg/j) étaient inférieurs aux recommandations. L’intervention du réseau permettait d’améliorer le statut nutritionnel des patients déments (+0,29 ± 0,07 point de MNA®/mois, p=0,003) ainsi que les apports énergétiques de tous les résidents à 4 mois. Les études « Epidémiologie de la Démence en Afrique Centrale » (EDAC) et « Epidemiology of Dementia in Central Africa » (EPIDEMCA) étaient menées en République Centrafricaine (RCA) et au Congo. Dans ces deux études, les personnes âgées démentes étaient plus souvent dénutries que les non démentes (EDAC : 34,7% vs 17,7%, p<0,0001 ; EPIDEMCA : 60,0% vs 31,3%, p<0,001). Dans l’étude EDAC, le fait de ne consommer qu’un repas par jour constituait un risque de dénutrition chez les déments (OR=7,23 [IC95% : 1,65-31,7, p=0,003]. De plus, les déments consommaient moins de fruits que les non déments (aucune consommation : 54,0% vs 36,7%, p=0,008). Dans l’étude EPIDEMCA, en RCA, une faible consommation d’oléagineux en zone rurale était associée à la présence d’une démence (OR=2,80 [IC95% : 1,02-7,70, p=0,046]), et une consommation d’alcool (quantités non étudiées) en population générale était négativement associée (OR=0,34 [IC95% : 0,14-0,83, p=0,018]). Aucune association n’était retrouvée au Congo. Des facteurs nutritionnels associés aux troubles cognitifs étaient identifiés : un Indice de Masse Corporelle <18,5kg/m2 , un périmètre brachial <24cm et une circonférence musculaire brachiale <5èmepercentile étaient associés en RCA à la démence (OR=2,66 [IC95% : 1,39-5,07, p=0,003] ; OR=1,97 [IC95% : 1,03-3,77, p=0,041] ; OR=2,94 [IC95% : 1,34-6,45, p=0,007], respectivement), et au Congo seule la circonférence musculaire brachiale <5èmepercentile était associée aux MCI (OR=3,61 [IC95% : 1,70-7,64, p=0,001]). Ces différents travaux permettent de disposer de nouvelles données concernant les patients atteints de SLA et de troubles cognitifs dans deux régions du globe. En France, une prise en charge par un réseau de santé est possible et semble améliorer le statut nutritionnel des personnes atteintes de MND. En Afrique Centrale, plusieurs facteurs associés aux troubles cognitifs ont été identifiés. Ces premiers résultats doivent être confirmés afin de proposer des moyens de prévention ciblés. / Neurodegenerative diseases (NDD) mainly concern neuromuscular diseases, including amyotrophic lateral sclerosis (ALS), dementia, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease. Due to the multiplicity of factors inducing a weight loss, the NDD are at risk of malnutrition, which can alter the evolution of these diseases and the quality of life of patients. The purpose of this work was to assess the nutritional status and / or the effect of treatment of patients with ALS and cognitive disorders (dementia and / or mild cognitive impairment [MCI]) in France with a health network, but also in Central Africa. The health network Limousin Nutrition (LINUT) realizes assessments and nutritional interventions in ALS patients at home and in residents of nursing homes (NH). The first evaluation by the network of ALS patients found more swallowing disorders than specialized consultation (60.0% vs. 47.5%) and taste disorders (43.8%), not further described in ALS. Improvements of practices were proposed. The network assessed also residents in NH, with or without dementia, initially and after a 4 months follow-up. Malnutrition affected more often demented patients (56.1% vs. 46.4% p=0.004), and energy intakes of all residents (26.4 ± 8.8 kcal/kg/d) were below the recommendations. The network intervention improved the nutritional status of patients with dementia (+0.29 ± 0.07 point of MNA®/month, p=0.003) and energy intake of all residents at 4 months. Two studies named

Magister Scientiae - MSc / Neurological diseases are socially disabling and often mortal. To efficiently combat these diseases, a deep understanding of involved cellular processes, gene functions and anatomy is required. However, differential regulation of genes across anatomy is not sufficiently well understood. This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon’s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy. / South Africa

The translation of mRNA into functional proteins is essential for all life. In eukaryotes, aberrant RNAs containing sequence features that stall or severely slow down ribosomes are subject to translation-dependent quality control. Targets include mRNAs encoding a strong secondary structure (No-Go Decay; NGD) or stretches of positively-charged amino acids (Peptide-dependent Translation Arrest/Ribosome Quality Control; PDTA/RQC), mRNAs lacking an in-frame stop codon (Non-Stop Decay; NSD), or defective 18S rRNAs (18S Nonfunctional rRNA Decay; 18S NRD). Previous work from our lab showed that the S. cerevisiae NGD factors DOM34 and HBS1, and PDTA/RQC factor ASC1, all participate in the kinetics of 18S NRD. Upon further investigation of 18S NRD, our research revealed the critical role of ribosomal protein S3 (RPS3), thus adding to the emerging evidence that the ribosome senses its own translational status. While aberrant mRNAs mentioned above can occur endogenously, damaging agents, such as oxidative stress or UV irradiation, can negatively affect the chemical integrity of RNA. Such lesions could lead to translation errors and ribosome stalling. However, current tools to monitor the fate of damaged RNA are quite limited and only provide a low-resolution picture. Therefore, we sought to develop a deep-sequencing method to detect damaged RNA, taking advantage of reverse transcriptase's ability to insert a mutation across a damaged site. Using oxidized RNA as a model damaged RNA, our preliminary data showed increased G>T mutations in oxidized RNA. This method provides the foundation for future work aimed at understanding how cells deal with damaged RNA.

Small interfering RNAs (siRNAs) are a promising class of drugs for treating genetically-defined diseases. Therapeutic siRNAs enable specific modulation of gene expression, but require chemical architecture that facilitates efficient in vivodelivery. siRNAs are informational drugs, therefore specificity for a target gene is defined by nucleotide sequence. Thus, developing a chemical scaffold that efficiently delivers siRNA to a particular tissue provides an opportunity to target any disease-associated gene in that tissue. The goal of this project was to develop a chemical scaffold that supports efficient siRNA delivery to the brain for the treatment of neurodegenerative diseases, specifically Huntington’s disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects 3 out of every 100,000 people worldwide. This disorder is caused by an expansion of CAG repeats in the huntingtin gene that results in significant atrophy in the striatum and cortex of the brain. Silencing of the huntingtin gene is considered a viable treatment option for HD. This project: 1) identified a hyper-functional sequence for siRNA targeting the huntingtin gene, 2) developed a fully chemically modified architecture for the siRNA sequence, and 3) identified a new structure for siRNA central nervous system (CNS) delivery—Divalent-siRNA (Di-siRNA). Di-siRNAs, which are composed of two fully chemically-stabilized, phosphorothioate-containing siRNAs connected by a linker, support potent and sustained gene modulation in the CNS of mice and non-human primates. In mice, Di-siRNAs induced potent silencing of huntingtin mRNA and protein throughout the brain one month after a single intracerebroventricular injection. Silencing persisted for at least six months, with the degree of gene silencing correlating to guide strand tissue accumulation levels. In Cynomolgus macaques, a bolus injection exhibited significant distribution and robust silencing throughout the brain and spinal cord without detectable toxicity. This new siRNA scaffold opens the CNS for RNAi-based gene modulation, creating a path towards developing treatments for genetically-defined neurological disorders.

<p> G93A SODI mice (G93A mice) are a transgenic model over-expressing a mutant human Cu/Zn-SOD gene, and are a model for amyotrophic lateral sclerosis (ALS), a predominantly motor neurodegenerative disease. Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyms (DG) occurs throughout the life. It is regulated by many pathological and physiological processes. There is controversy with respect to the basal level of hippocampal neurogenesis and its response to exercise in neurodegenerative diseases and their mouse models. Little information regarding hippocampal neurogenesis is available in G93A mice. The present study was designed to study the impact of treadmill exercise and sex differences on hippocampal neurogenesis in this model. In addition, potential molecular mechanisms regulating hippocampal neurogenesis including growth factors (BDNF and IGFl) and oxidative stress (SOD2, catalase, 8-0Hdg, and 3-NT) were also addressed in the study. Bromodeoxyuridine (BrdU) was used to label newly generated cells. G93A and wild type (WT) mice were subjected to treadmill exercise (EX) or a sedentary (SEO) lifestyle. Immunohistochemistry was used to detect BrdU labeled newly proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress. BDNF and IGFl mRNA expression was assessed by in situ hybridization. Results showed that (1) G93A mice had an elevated basal level of hippocampal neurogenesis for both cell survival and neuronal differentiation, a growth factor (BDNF mRNA), and an oxidative stress marker (NT), as compared to wild type sedentary mice. (2) Treadmill running did not show any further effect on hippocampal neurogenesis, growth factors, oxidative stress, and antioxidant enzymes in G93A mice, while treadmill running promoted hippocampal neurogenes1s and expression of the growth factor (BDNF mRNA), and lowered oxidative stress (8-0Hdg) in WT mice. (3) There also were sex differences in hippocampal neurogenesis in G93A mice, whereby male G93A mice had a significant higher level of cell proliferation but a lower level of survival than female G93A mice. (4) The DG BDNF mRNA was associated with cell survival and neuronal differentiation in sedentary G93A mice, suggesting that BDNF is associated with a higher basal level of hippocampal neurogenesis in G93A mice. We conclude that G93A mice are more permissive in the context of hippocampal neurogenesis, which is associated with elevated DG BDNF mRNA expression. Running did not have impact on hippocampal neurogenesis and BDNF mRNA expression in G93A mice, probably due to a 'ceiling effect' of the already heightened basal levels of hippocampal neurogenesis and BDNF mRNA in this model. In addition, sex differences also affect hippocampal neurogenes1s, but the further study is needed to clarify the underlying molecular mechanisms. </p> / Thesis / Doctor of Philosophy (PhD)

<p>Aging erodes motivation, cognition, sensory modalities and physical capacities, effectively depleting quality of life. Declining sensory, cognitive and motor function are reliable biomarkers of aging and mortality risk. These declines are associated with dysregulation of systemic and cellular processes. We developed a complex dietary supplement (DSP) designed to ameliorate five mechanisms of aging (oxidative processes, inflammation, mitochondrial function, insulin resistance and membrane integrity). Remarkably, normal mice fed the DSP retained youthful functionality into old ages, reflecting slower aging rates. Marked improvements in motor function, memory capacity, spatial learning, muscle strength, visual acuity, olfaction, fecundity and important behavioral functions were observed in aging supplemented mice. Conversely, untreated control animals showed age-related declines in all of the above. Functional improvements were associated with reduced oxidative damage, elevated mitochondrial activity, positive cellular energy balance, improved glucose tolerance, boosted neurotransmitters, greater synaptic density and higher neuronal numbers throughout the brain. A 30% reduction in cancer rates was also documented for DSP treated p53+/- mice. The vast functional benefits greatly exceed the modest longevity extension (11%) in normal supplemented mice. For aging humans, maintaining functionality and performance into later years may provide greater socioeconomic and health benefits than simply prolonging lifespan. Implications of these findings extend to common age-related pathologies including dementia and neurodegenerative diseases, diabetes, cancer, sarcopenia and age-related macular degeneration. Although identifying the role of specific ingredients remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.</p> / Doctor of Philosophy (PhD)

No description available.

Les maladies neurodégénératives, telles que la maladie d'Alzheimer (AD) et Charcot Marie Tooth (CMT), sont des maladies complexes. Leurs mécanismes pathologiques ne sont toujours pas bien compris et les progrès dans la recherche et le développement de nouvelles thérapies potentielles modifiant la maladie sont lents. Les données catégorielles, comme les échelles de notation et les données sur les études d'association génomique (GWAS), sont largement utilisées dans les maladies neurodégénératives dans le diagnostic, la prédiction et le suivi de la progression. Il est important de comprendre et d'interpréter ces données correctement si nous voulons améliorer la recherche sur les maladies neurodégénératives. Le but de cette thèse est d'utiliser la théorie psychométrique moderne: théorie de la réponse d’item pour analyser ces données catégoriques afin de mieux comprendre les maladies neurodégénératives et de faciliter la recherche de médicaments correspondante. Tout d'abord, nous avons appliqué l'analyse de Rasch afin d'évaluer la validité du score de neuropathie Charcot-Marie-Tooth (CMTNS), un critère important d'évaluation principal pour les essais cliniques de la maladie de CMT. Nous avons ensuite adapté le modèle Rasch à l'analyse des associations génétiques pour identifier les gènes associés à la maladie d'Alzheimer. Cette méthode résume les génotypes catégoriques de plusieurs marqueurs génétiques tels que les polymorphisme nucléotidique (SNPs) en un seul score génétique. Enfin, nous avons calculé l'information mutuelle basée sur la théorie de réponse d’item pour sélectionner les items sensibles dans ADAS-cog, une mesure de fonctionnement cognitif la plus utilisées dans les études de la maladie d'Alzheimer, afin de mieux évaluer le progrès de la maladie. / Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Charcot Marie Tooth (CMT), are complex diseases. Their pathological mechanisms are still not well understood, and the progress in the research and development of new potential disease-modifying therapies is slow. Categorical data like rating scales and Genome-Wide Association Studies (GWAS) data are widely utilized in the neurodegenerative diseases in the diagnosis, prediction and progression monitor. It is important to understand and interpret these data correctly if we want to improve the disease research. The purpose of this thesis is to use the modern psychometric Item Response Theory to analyze these categorical data for better understanding the neurodegenerative diseases and facilitating the corresponding drug research. First, we applied the Rasch analysis in order to assess the validity of the Charcot-Marie-Tooth Neuropathy Score (CMTNS), a main endpoint for the CMT disease clinical trials. We then adapted the Rasch model to the analysis of genetic associations and used to identify genes associated with Alzheimer’s disease by summarizing the categorical genotypes of several genetic markers such as Single Nucleotide Polymorphisms (SNPs) into one genetic score. Finally, to select sensitive items in the most used psychometrical tests for Alzheimer’s disease, we calculated the mutual information based on the item response model to evaluate the sensitivity of each item on the ADAS-cog scale.

No description available.

Tesis por compendio / [ES] El aumento del envejecimiento de la población a nivel mundial y la limitada eficacia de los tratamientos disponibles para la demencia plantean la necesidad de desarrollar intervenciones dirigidas al envejecimiento y a las enfermedades neurodegenerativas. También se hace necesario promover cambios relacionados con la percepción negativa sobre la vejez en la sociedad. Ante estos planteamientos se está informando de los posibles beneficios terapéuticos de las intervenciones basadas en las artes, como la arteterapia, en la promoción de la salud, prevención de la demencia y manejo de la sintomatología asociada. Debido al interés de este tema nos propusimos evaluar los principales efectos de la arteterapia en el envejecimiento y enfermedades neurodegenerativas, analizar los posibles beneficios de esta terapia dirigida a personas mayores durante la pandemia y conocer los efectos del arte respuesta como activismo artístico para promover el cambio social en los estereotipos asociados al envejecimiento. Con el fin de alcanzar estos objetivos se plantearon 5 estudios que han dado lugar a los 5 artículos publicados en revistas de impacto que componen la tesis doctoral. El primer estudio incluye una revisión sistemática que analiza los beneficios de la arteterapia en personas con Enfermedad de Alzheimer (EA): los resultados informan de mejoras en bienestar, calidad de vida, estado anímico y depresión. El segundo artículo muestra un estudio de un caso de Parálisis Supranuclear Progresiva (un parkinsonismo atípico) evaluando posibles beneficios de la arteterapia en la sintomatología asociada a la enfermedad. Los resultados informan de mejoras significativas en expresión emocional, aspectos conductuales y relaciones sociales. El tercer trabajo analiza la relación entre EA y el duelo crónico basándose en un estudio de caso de EA, evaluando los efectos de la arteterapia en los síntomas cognitivos, somáticos y psicológicos. Se observó un impacto positivo en la expresión emocional, aspectos cognitivos (concentración, control, memoria), relaciones sociales y cambios en el sentido de identidad. El cuarto estudio describe una intervención de arteterapia en un grupo de mujeres de edad avanzada realizada durante las restricciones impuestas por la pandemia analizando las dificultades asociadas a este periodo y proponiendo su abordaje a través de la arteterapia. Los resultados sugieren mejoras en aspectos cognitivos (concentración, memoria y atención), expresión e identificación emocional, socialización y disminución de la ansiedad. El quinto estudio consta de dos proyectos relacionados (exposición virtual y talleres intergeneracionales) que tienen como denominador común el arte respuesta como activismo artístico, promoviendo la concienciación y el cambio social, y utilizando el arte respuesta para dar sentido y significado a las reflexiones relacionadas con el envejecimiento. Las experiencias incluidas en las 5 publicaciones contribuyen a generar avance del conocimiento acerca de las posibles aplicaciones de la arteterapia en el envejecimiento, enfermedades neurodegenerativas y prevención de la demencia. También se muestra su utilidad para contrarrestar la privación sensorial y social que conllevan las situaciones de crisis como las vividas durante la pandemia. Además, se han diseñado intervenciones basadas en el activismo artístico que pueden contribuir a desafiar estereotipos y superar actitudes negativas de la sociedad hacia la vejez. En futuros estudios sería de interés realizar intervenciones en muestras más amplias y con seguimiento longitudinal, así como el uso complementario de biomarcadores o técnicas de neuroimagen para evaluar los resultados de la intervención en la población de edad avanzada. Estas intervenciones arteterapéuticas pueden contribuir a crear experiencias participativas intergeneracionales basadas en las artes sobre la experiencia del envejecimiento / [CA] L'augment de l'envelliment de la població a nivell mundial i la limitada eficàcia dels tractaments disponibles per a la demència plantegen la necessitat de desenvolupar intervencions dirigides a l'envelliment i a les malalties neurodegeneratives. També es fa necessari promoure canvis relacionats amb la percepció negativa sobre la vellesa en la societat. Davant estos plantejaments s'està informant dels possibles beneficis terapèutics de les intervencions basades en les arts, com l'artteràpia, en la promoció de la salut, prevenció de la demència i maneig de la simptomatologia associada. A causa de l'interés d'este tema ens vam proposar avaluar els principals efectes de l'artteràpia en l'envelliment i malalties neurodegeneratives, analitzar els possibles beneficis d'esta teràpia dirigida a persones majors durant la pandèmia i conéixer els efectes de l'art resposta com a activisme artístic per a promoure el canvi social en els estereotips associats a l'envelliment. Amb la finalitat d'aconseguir estos objectius es van plantejar 5 estudis que han donat lloc als 5 articles publicats en revistes d'impacte que componen la tesi doctoral. El primer estudi inclou una revisió sistemàtica que analitza els beneficis de l'artteràpia en persones amb Malaltia d'Alzheimer: els resultats informen de millores en benestar, qualitat de vida, estat anímic i depressió. El segon article mostra un estudi de cas de Paràlisis Supranuclear Progressiva (un parkinsonisme atípic) avaluant possibles beneficis de l'artteràpia en la simptomatologia associada a la malaltia. Els resultats informen de millores significatives en expressió emocional, aspectes conductuals i relacions socials. El tercer treball analitza la relació entre Malaltia d'Alzheimer i el dol crònic basant-se en un estudi de un cas de Malaltia d'Alzheimer, avaluant els efectes de l'artteràpia en els símptomes cognitius, somàtics i psicològics. Es va observar un impacte positiu en l'expressió emocional, aspectes cognitius (concentració, control, memòria), relacions socials i canvis en el sentit d'identitat. El quart estudi descriu una intervenció d'artteràpia en un grup de dones d'edat avançada realitzada durant les restriccions imposades per la pandèmia analitzant les dificultats associades a este període i proposant el seu abordatge a través de l'artteràpia. Els resultats suggerixen millores en aspectes cognitius (concentració, memòria i atenció), expressió i identificació emocional, socialització i disminució de l'ansietat. El quint estudi consta de dos projectes relacionats (exposició virtual i tallers intergeneracionals) que tenen com a denominador comú l'art resposta com a activisme artístic, promovent la conscienciació i canvi social, i utilitzant l'art resposta per a donar sentit i significat a les reflexions relacionades amb l'envelliment. Les experiències incloses en les 5 publicacions contribuïxen a generar avanç del coneixement sobre les possibles aplicacions de l'artteràpia en l'envelliment, malalties neurodegeneratives i prevenció de la demència. També es mostra la seua utilitat per a contrarestar la privació sensorial i social que comporten les situacions de crisis com les viscudes durant la pandèmia. A més, s'han dissenyat intervencions basades en l'activisme artístic que poden contribuir a desafiar estereotips i superar actituds negatives de la societat cap a la vellesa. En futurs estudis seria d'interés realitzar intervencions en mostres més àmplies i amb seguiment longitudinal, així com l'ús complementari de biomarcadors o tècniques de neuroimatgeria per a avaluar els resultats de la intervenció en la població d'edat avançada. Estes intervencions artterapèutiques poden contribuir a crear experiències participatives intergeneracionals basades en les arts sobre l'experiència de l'envelliment / [EN] The increasing aging of the world's population and the limited effectiveness of available treatments for dementia increase the need to develop interventions that target aging and neurodegenerative diseases. There is also a need to promote changes in negative societal perceptions of old age. In light of these approaches, the potential therapeutic benefits of arts-based interventions, such as art therapy, in health promotion, dementia prevention and management of associated symptoms are being reported. Due to the interest of this topic, we proposed to evaluate the main effects of art therapy in ageing and neurodegenerative diseases, to analyze the possible benefits of this therapy for older people during the pandemic, and to know the effects of response art as artistic activism to promote social change in the stereotypes associated with ageing. In order to achieve these objectives, 5 studies were proposed, which gave rise to the 5 articles published in high impact journals that make up the thesis. The first study is a systematic review analyzing the benefits of art therapy in people with Alzheimer's disease: the results report improvements in well-being, quality of life, mood and depression. The second article presents a case study of a person living with Progressive Supranuclear Palsy (atypical parkinsonism), evaluating the potential benefits of art therapy on the symptomatology associated with the disease. The results report significant improvements in emotional expression, behavioral aspects and social relationships. The third paper analyses the relationship between Alzheimer's disease and chronic grief based on a case study of a woman diagnosed with Alzheimer's disease, evaluating the effects of art therapy on cognitive, somatic and psychological symptoms. Positive effects were observed on emotional expression, cognitive aspects (concentration, control, memory), social relationships and changes in sense of identity. The fourth study describes an art therapy intervention with a group of old women, carried out during the restrictions imposed by the pandemic, analyzing the difficulties associated with this period and proposing an approach through art therapy. The results suggest improvements in cognitive aspects (concentration, memory and attention), emotional expression and identification, socialization and reduction of anxiety. The fifth study consists of two related projects (virtual exhibition and intergenerational workshops) that share the common denominator of Response Art as artistic activism, promoting awareness and social change, and using Response Art to give sense and meaning to reflections related to aging. The experiences included in the 5 publications contribute to the advancement of knowledge about the possible applications of art therapy in ageing, neurodegenerative diseases and dementia prevention. They also demonstrate its usefulness in counteracting the sensory and social deprivation associated with crisis situations such as those experienced during the pandemic. In addition, interventions based on artistic activism have been developed that can help to challenge stereotypes and overcome negative societal attitudes towards old age. In future studies, it would be interesting to carry out interventions in larger samples and with longitudinal follow-up, as well as the complementary use of biomarkers or neuroimaging techniques to assess the results of the intervention with older people. These art-therapeutic interventions can contribute to the creation of art-based intergenerational participatory experiences of aging / Marco Martínez, P. (2024). Arteterapia en el envejecimiento y enfermedades neurodegenerativas. Experiencias basadas en la prevención, intervención y el activismo artístico [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/206125 / Compendio