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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Measuring the Usability of eHealth Solutions for Patients With Parkinson Disease: Observational Study

Bendig, Jonas, Spanz, Anja, Leidig, Jana, Frank, Anika, Stahr, Marcus, Reichmann, Heinz, Loewenbrück, Kai F., Falkenburger, Björn H. 22 February 2024 (has links)
Background: Parkinson disease (PD) is a neurodegenerative disorder with a variety of motor and nonmotor symptoms. Many of these symptoms can be monitored by eHealth solutions, including smartphone apps, wearable sensors, and camera systems. The usability of such systems is a key factor in long-term use, but not much is known about the predictors of successful use and preferable methods to assess usability in patients with PD. Objective: This study tested methods to assess usability and determined prerequisites for successful use in patients with PD. - Methods: We performed comprehensive usability assessments with 18 patients with PD using a mixed methods usability battery containing the System Usability Scale, a rater-based evaluation of device-specific tasks, and qualitative interviews. Each patient performed the usability battery with 2 of 3 randomly assigned devices: a tablet app, wearable sensors, and a camera system. The usability battery was administered at the beginning and at the end of a 4-day testing period. Between usability batteries, the systems were used by the patients during 3 sessions of motor assessments (wearable sensors and camera system) and at the movement disorder ward (tablet app). - Results: In this study, the rater-based evaluation of tasks discriminated the best between the 3 eHealth solutions, whereas subjective modalities such as the System Usability Scale were not able to distinguish between the systems. Successful use was associated with different clinical characteristics for each system: eHealth literacy and cognitive function predicted successful use of the tablet app, and bettermotor function and lower age correlated with the independent use of the camera system. The successful use of the wearable sensors was independent of clinical characteristics. Unfortunately, patients who were not able to use the devices well provided few improvement suggestions in qualitative interviews. Conclusions: eHealth solutions should be developed with a specific set of patients in mind and subsequently tested in this cohort. For a complete picture, usability assessments should include a rater-based evaluation of task performance, and there is a need to develop strategies to circumvent the underrepresentation of poorly performing patients in qualitative usability research.
72

<b>Charactering the impact of traumatic injury on neurodegenerative disease risk using engineered cell and tissue model</b>

Junkai Xie (17130850) 12 October 2023 (has links)
<p dir="ltr">Neurotrauma encompasses a broad category of injuries affecting the central nervous system (CNS), which includes both the traumatic brain injury (TBI) and spinal cord injury (SCI). These injuries can result from various causes, including accidents, falls, sports-related incidents, and other traumatic events, affecting millions of individuals annually. Traumatic injuries are the leading cause of disability, and moreover are associated with elevated risk of developing cognitive impairments and neurodegenerative diseases (ND) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). The elevated ND risk arising from neurotrauma poses significant burdens on healthcare systems and affect life quality of affected individuals, emphasizing the critical need for research aimed at understanding the underlying mechanisms conferring ND risk from the lesion center to CNS. The goal of my thesis is to understand persistent molecular changes post SCI associated with ND using a combination of a rat animal model and neuronal cultures derived from human induced pluripotent stem cells.</p><p dir="ltr">I started with Sprague-Dawley rats with T10 spinal cord contusive injury; and assessed immediate and persistent changes in transcriptomic and epigenetic markers via next generation sequencing (NGS) at primary lesion site and distal spinal cord tissue. Along with global changes in chromatin arrangements and DNA methylation, we observed significant transcriptomic changes enriched for pathways of inflammatory responses, and synaptogenesis. These changes were further verified using immunohistochemistry and super resolution microscopy. To further understand the long-term brain abnormality linked to SCI, we investigated persistent alterations in the composition and molecular profiles of both the male and female motor cortex 30 days after injury. Immunohistochemistry revealed that SCI leads to neuronal loss and changes in synaptic density and morphology; and significant alterations in the neuron-astrocyte ratio and astrocyte morphology, in male motor cortex supporting our hypothesis that SCI may increase the risk of neurodegeneration by affecting the motor cortex. Comparison of transcriptomic data collected at a sub-acute stage in male rats, namely 7 days post injury, with 30 days post injury, identified persistent and de novo changes that occur primarily after recovery of spinal cord injury, which are enriched for neuronal and synaptic function related pathways. Interestingly, neuroendocrine-related pathways were prominently implicated at the chronic stage of SCI, with Esr1 identified as a major upstream regulator offering protective effects in females that did not exhibit significant alterations in cellular composition or morphology after SCI. Collectively, our study paved the way towards understanding sexual dimorphism in brains after spinal cord injury and provides a plausible connection between spinal cord injury and neurodegeneration later in life that were further investigated using a humanized culture model.</p><p dir="ltr">We established the feasibility of using hiPSC derived neurons to examine long term neurotoxic mechanism using lead (Pb) as a model chemical with strong associations with elevated AD risks later in life. A similar culture system was then used to assess persistent neurotoxicity of acrolein, a chemical that is known to emerge in brains post traumatic injury. We found that acrolein induced alterations in neuronal network morphology, synaptic density, and excitability. Furthermore, acrolein exposure negatively impacted mitochondrial function and persistently altered neuronal resilience towards a secondary stressor of mitochondria, namely MPP+. Acrolein exposure also alters the expression of tau and tau phosphorylation which collectively result in increased cellular vulnerability toward paired helical filament (PHF-tau) seeding, a known neurotoxin associated with ND. These findings collectively provide molecular insights as to how acrolein can partake alterations in neural function and resilience to stressors; and relay ND risks in neurotrauma patients later in life.</p><p dir="ltr">In conclusion, our comprehensive investigation employing both rat and hiPSC models uncovers plausible molecular pathways connecting SCI to neurodegenerative diseases, providing insights into the enduring consequences of these injuries on affected patients.</p>
73

Oral hälsa hos individer med Parkinson sjukdom : En allmän litteraturstudie / Oral health in individuals with Parkinson's disease

Isaac, lulia, Shemoun, Mariam January 2022 (has links)
Syfte: Studiens syfte var att beskriva oral hälsa hos individer med Parkinson sjukdom (PS). Metod:Studiedesignen var i form av allmän litteraturstudie där tre databaser användes för sökning efter vetenskapliga artiklar (DOSS, CINAHL och MEDLINE). Efter tillämpning av inklusions-, exklusionskriterier, passande sökord samt genomförande av kvalitetsgranskning, valdes totalt 19 vetenskapliga artiklar. Resultat: Oral hygien tenderade till att vara sämre hos individer med PS. Resultatet visade att xerostomi och hyposalivation var vanligt förkommande hos individer med PS. Karies, gingivit och parodontit visades även hos individer med PS där bland annat parodontala mätningar visades vara högre till andel hos dessa individer. Andra orala tillstånd som visades bland individer med PS var dregling, dysfagi, halitosis och angulär cheilit. Slutsats: Hos individer med PS visades orala hälsan var sämre jämfört med individer utan PS. Risken att utsättas för orala sjukdomar exempelvis karies, gingivit och parodontit var högre hos individer med PS, där både läkemedelsintag och nedsatt motorik har en inverkan. / Aim: The aim was to describe oral health in individuals with Parkinson's disease (PD). Method: The study design was a general literature study where three databases were used to search for scientific articles (DOSS, CINAHL and MEDLINE). After applying inclusion, exclusion criteria, proper keywords and conducting a quality review, a total of 19 scientific articles were selected. Result: Oral hygiene tended to be worse in patients with PD. The results showed that xerostomia and hyposalivation are common in patients with PD. Caries, gingivitis and periodontitis were also shown among patients with PD where, among other things, periodontal measurements were shown to be higher in proportion in these individuals. Other oral conditions that were shown among individuals with PD were drooling, dysphagia, halitosis and angular cheilitis. Conclusion: Oral health was shown to be worse among individuals with PD compared to individuals without PD. The risk of being exposed to oral diseases such as caries, gingivitis and periodontitis was higher among these individuals where both drug intake and impaired motor skills have an effect.
74

Arteterapia en el envejecimiento y enfermedades neurodegenerativas. Experiencias basadas en la prevención, intervención y el activismo artístico.

Marco Martínez, Patricia 15 July 2024 (has links)
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
75

Étude des mécanismes moléculaires impliqués dans la mort neuronale induite par le peptide de ß-amyloïde soluble : recherche et validation fonctionnelle de cibles cellulaires / Molecular mechanisms involved in soluble ß amyloid peptide-induced cell death : characterization and functional validation of therapeutic targets

Youssef, Ihsen 31 October 2006 (has links)
Le vieillissement des populations est corrélé à l’augmentation des pathologies neurodégénératives liées à l’âge, plus particulièrement la maladie d’Alzheimer. La recherche de marqueurs précoces de la maladie ainsi que l’élaboration de nouvelles stratégies thérapeutiques constituent un enjeu de taille. Parmi les mécanismes moléculaires de la formation des plaques amyloïdes actuellement explorés, les formes oligomériques tronquées de peptide amyloïde (Aß), notamment le peptide Aß3(?pE)??42? retrouvé à des stades précoces de la maladie, joueraient un rôle déterminant. Ces travaux de thèse ont permis de montrer, dans un premier temps, que l’injection intracérébrale de ce peptide chez la souris entraîne des altérations de la mémoire de travail et des capacités d’apprentissage, associées à une accumulation d’espèces réactives dérivées de l’oxygène dans des régions cérébrales spécifiques (hippocampe et bulbes olfactifs) de ces animaux. Des essais menés in vitro sur des cultures primaires de neurones de souris montrent leur implication dans les voies apoptotiques impliquant l’activation des caspases et la cascade métabolique de l’acide arachidonique. La seconde étape de ces travaux a constitué en l’étude des effets protecteurs d’un peptide antiapoptotique d’origine endogène, l’humanine (HN) et son variant S14G (HNG). In vitro, un effet protecteur de ces peptides a été mesuré après traitement de neurones en culture par le peptide A[bêta]3?(pE)42.??? Les résultats les plus marquants résident dans les observations faites in vivo : en effet, ces peptides inhibent l’effet délétère de l’injection intracérébroventriculaire du peptide Aß3?(pE??)42?? en restaurant les performances mnésiques des animaux dans les tests comportementaux. A la lumière de ces résultats, les peptides HN pourraient constituer de nouveaux outils thérapeutiques dans le traitement ou la prévention des dommages cellulaires précoces liés à la présence des oligomères solubles du peptide Aß / Aging of population is correlated to the increase of neurodegenerative disease, more particularly Alzheimer disease. Defining early diagnostic markers and new therapeutic strategies are highly relevant. Among the molecular pathways which are currently developed, N-terminal-truncated forms of amyloid-ß (Aß) peptide have been recently suggested to play a pivotal role in the disease. Among them, Aß3(?pE)42 ?peptide is the dominant Aß species in amyloid plaques. We first investigated the effects of soluble oligomeric Aß3(pE) 42 after intracerebroventricular injection on mice learning capacities and the molecular mechanisms of in vitro neurotoxicity. Mice injected with soluble Aß3(pE) 42 displayed impaired spatial working memory and delayed memory acquisition. These cognitive alterations were associated with free radical overproduction in hippocampus and olfactory bulbs. In vitro, Aß3(pE) 42 oligomers induced a redox-sensitive neuronal apoptosis involving caspase activation and an arachidonic acid-dependent pathway. The second goal of this work was to investigate the protective effects of the apoptosis rescue endogenous peptide humanin (HN) and its S14G mutant (HNG). In vitro, we measured their inhibitory effect on neuronal death and apoptotic events resulting from soluble Ab oligomer treatment. What’s of particular interest is the in vivo restoration of soluble Aß3(pE) 42 oligomer-induced mnesic impairment. Thus, HN peptides might serve as new drug candidates for treatment or prevention of early cellular damages linked to soluble A[bêta] oligomers
76

Changes in gene expression linked to Alzheimer's disease and "healthy" cognitive aging

Navarro Sala, Magdalena 05 July 2018 (has links)
No description available.
77

Étude de la perfusion cérébrale régionale dans le trouble comportemental en sommeil paradoxal

Vendette, Mélanie 12 1900 (has links)
No description available.
78

Exposure to Estrogenic Endocrine Disrupting Chemicals and Brain Health

Preciados, Mark 11 May 2018 (has links)
The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that are both estrogen and EEDC-sensitive, we found several genes involved in the gene pathways of Alzheimer’s disease (AD): APBB2, EIF2S1, ENO1, MAPT, and PAXIP1. Using the Center for Disease Control and Prevention (CDC), National Health and Nutrition Examination Survey (NHANES) 2011-2014 datasets to assess EEDC bioburden and associations with surrogate indicators of brain health, which include cognitive scores, memory questions, and taste and smell data, we found phthalate bioburden to be significantly higher in those with adverse brain health vii and significantly higher in females. In our logistic regression model when controlling for all known and suspected covariates in AD, in females, the phthalates in females ECP, MBP, MOH, MZP, and MIB in males and the phthalates COP, ECP, MBP, MC1, MEP, MHH, MOH, and MIB were significantly associated with poor cognitive test scores, poor memory, and taste and smell dysfunction. Among the metalloestrogens, Cd bioburden was higher in those with poor cognitive performance, poor memory, and taste and smell dysfunction, with the trend more significant in males. Among oral contraceptive (OC) and HRT (hormone replacement therapy) use, in our logistic regression model when controlling for all known and suspected covariates in AD, past OC and HRT use was associated with better cognitive test scores. The study provides further evidence of the complex role EEDCs play in overall brain health through other biological mechanisms and fills a gap in knowledge that demonstrates EEDCs effects on brain health in a geriatric age population.
79

Étude de la perfusion cérébrale régionale dans le trouble comportemental en sommeil paradoxal

Vendette, Mélanie 12 1900 (has links)
Le trouble comportemental en sommeil paradoxal (TCSP) se caractérise par une perte de l’atonie musculaire en sommeil paradoxal et par des manifestations motrices élaborées souvent associées au contenu onirique. Le TCSP peut apparaître sous une forme idiopathique (TCSPi), mais il est fréquemment lié à certains désordres neurodégénératifs, dont les synucléinopathies. Des marqueurs biologiques des synucléinopathies, tels que la présence d’anomalies au plan de la motricité, de la détection des odeurs ainsi que de la discrimination des couleurs, ont été retrouvés dans le TCSPi. De plus, des perturbations de l’activité cérébrale en neuroimagerie ainsi que du fonctionnement cognitif ont été observées chez ces patients. Des études ont démontré que le TCSPi pouvait précéder l’apparition d’une maladie de Parkinson (MP) ou d’une démence à corps de Lewy (DCL). Ceci suggère que le TCSPi représenterait un facteur de risque des synucléinopathies. L’objectif principal du présent projet est d’étudier les anomalies du débit sanguin cérébral régional (DSCr) de repos avec la tomographie par émission monophotonique (TEM) dans le TCSPi. Deux études ont été réalisées. La première visait à comparer le DSCr entre des patients avec un TCSPi et des sujets sains, puis d’explorer la relation entre l’activité cérébrale et la présence de marqueurs biologiques des synucléinopathies. Les résultats ont montré une diminution de la perfusion cérébrale dans les régions frontales et pariétales ainsi qu’une augmentation de la perfusion au niveau du pont, du putamen et des hippocampes chez les patients avec un TCSPi. Une relation significative entre la performance des sujets avec un TCSPi à une épreuve de discrimination des couleurs et la perfusion cérébrale au niveau des régions frontales et occipitales a été mise en évidence. Dans l’ensemble, ces résultats ont démontré des anomalies du DSCr chez les patients avec un TCSPi qui sont similaires à celles observées par d’autres études en neuroimagerie dans la MP. Ceci suggère des atteintes neuroanatomiques semblables entre ces pathologies. La seconde étude en TEM a été effectuée dans le but d’examiner les modifications du DSCr associées aux perturbations du fonctionnement cognitif dans le TCSPi. Pour ce faire, le DSCr a été comparé entre un sous-groupe de patients avec un TCSPi et un trouble cognitif léger (TCL), un sous-groupe de patients avec un TCSPi sans TCL et un groupe de sujets sains. Les résultats ont montré que seuls les patients avec un TCSPi et un TCL présentaient une diminution de la perfusion cérébrale dans les aires corticales postérieures (occipitales et temporo-pariétales). Ces observations sont similaires à celles rapportées dans la MP avec démence et la DCL dans les études en neuroimagerie. En conclusion, les résultats de ces deux études ont montré des perturbations du DSCr dans le TCSPi, similaires à celles observées dans les synucléinopathies. Par ailleurs, nos résultats ont mis en évidence que les patients avec un TCSPi et un TCL présentaient les mêmes anomalies de la perfusion cérébrale que les patients avec une MP avec démence et/ou une DCL. La présence de tels marqueurs des synucléinopathies dans le TCSPi suggère que ces patients pourraient être plus à risque d’évoluer vers ce type de maladie neurodégénérative. / Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal atonia during REM sleep and elaborate motor activity associated with dreams. RBD may occur in an idiopathic form (iRBD), but is frequent in neurodegenerative diseases characterized by alpha-synuclein deposition such as Parkinson’s disease (PD) and dementia with Lewy bodjes (DLB). Biomarkers of synucleinopathies, such as motor, olfaction and color discrimination dysfunctions have been found in patients with iRBD. Moreover, impaired cerebral activities with neuroimaging and cognitive perturbations have also been detected in those patients. Longitudinal studies have demonstrated that iRBD might precede PD or DLB by several years. This suggests that iRBD could represent a risk factor of synucleinopathies. The goal of the present research was to investigate the resting regional cerebral blood flow (rCBF) in an iRBD sample using single photon emission computerized tomography (SPECT) neuroimaging. This led to two different studies. The aim of the first study was to compare the rCBF between a group of patients with iRBD and a group of healthy control subjects, and to explore correlations between rCBF of iRBD patients and markers of synucleinopathies. The results of this study showed that compared to controls, iRBD patients had decreased perfusion in frontal and parietal cortical regions and an increased perfusion in pons, putamen and hippocampus bilaterally. Moreover, a significant correlation between brain perfusion in frontal and occipital cortex and performance on a color discrimination test was found in iRBD patients. The brain perfusion anomalies observed in our iRBD patients are similar to those observed in PD in functional neuroimaging studies, suggesting similar neuroanatomic basis between these two pathologies. The objective of the second study was to investigate brain perfusion changes associated with mild cognitive impairment (MCI) in iRBD. We compared rCBF of a sub-group of patients with iRBD and MCI, a sub-group of patients with iRBD without MCI and a group of healthy control subjects. The results showed that only iRBD with MCI showed decreased perfusion in posterior brain regions, in occipital and temporo-parietal areas. These anomalies found in iRBD with MCI are similar to those reported in other studies in PD patients with dementia (PDD) and DLB in neuroimaging studies. To conclude, the results of this research showed brain perfusion abnormalities in iRBD patients similar to those found in synucleinopathies. One of our studies demonstrated a specific pattern of cerebral anomalies with SPECT, similar to those found in PDD and DLB, in patients with iRBD and MCI compared to iRBD without MCI. These biomarkers of synucleinopathies in iRBD suggest that these patients might be at higher risk to develop a neurodegenerative disease associated with alpha synuclein deposition.
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Impact de l’état et de la prise en charge nutritionnels dans les maladies neurodégénératives : Approche neuroépidémiologique / Impact of nutritional status and nutritional care in neurodegenerative diseases : Neuroepidemiologica

Jésus, Pierre 19 December 2014 (has links)
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

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