Data was provided by researchers of the Einstein Aging Study (EAS) of the Albert Einstein College of Medicine, Yeshiva University whom statistically analyzed data from the Bronx Aging Study cohort, concluding that participation in cognitive leisure activities and one physical activity, dancing, were associated with a reduced risk of dementia [1]. We explore data from a second (the EAS) cohort, utilizing Cox Proportional-Hazards and extended Cox regression [13]. Cognitive leisure activities in general, and particularly doing crossword puzzles, reading books, watching television, and emailing are associated with a reduced risk of dementia. Doing aerobics, learning computer programming, babysitting, dancing, jogging singing, and weight training are associated with an increased risk of dementia. Participation in cognitive leisure activities in general, and reading books in particular, remains highly significant even after adjustment for well-known risk factors [14] such as: age, cognitive status, depression, medical illnesses, gender, ethnicity, education and economic status. / by Carrie Stevens. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

This qualitative case study investigated the impact of sand tray on individuals diagnosed with Alzheimer’s and other forms of dementia. Four participants successfully completed the creation of sand trays while the researcher observed, interviewed, and documented the individual sand trays. The intervention established that sand tray allows the dementia patient to kinesthetically connect to their inner cognitions through the intentional symbolic expression offered by this unique therapeutic medium. Using a series of eight sand trays of varying thematic concepts, the participants were offered a modality to facilitate a synthesization of their continued individuation, presenting a possible neural pathway to connect and express thoughts, feelings, emotions, concerns, challenges, and fears. The findings of this study include the fact that all trays were classified as “empty” and that the majority of the participants placed objects almost exclusively on the right side of the tray, which is commonly associated with the concreteor conscious side. The use of sand tray allowed each individual the opportunity to create autobiographies in the sand and literally navigate through time – past, present, and future, confronting fears, expressing hope and possibilities. The results of the research study offer insight into the psychotherapeutic effects of using sand tray with dementia patients, as well as a better understanding of the cognitive and expressive abilities and limitations of an individual with impaired memory. The results also offer insight into the difficulties with short-term memory in this population and possibly indicate a potential means for monitoring cognitive decline. Keywords: Neurocognitive disorder, Alzheimer’s, dementia, sand tray, play therapy / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2013.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T14:19:27Z No. of bitstreams: 1 KELLEN ROCHA.pdf: 1430079 bytes, checksum: ba3882603d46f2a9824b73319d20cd73 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T14:19:44Z (GMT) No. of bitstreams: 1 KELLEN ROCHA.pdf: 1430079 bytes, checksum: ba3882603d46f2a9824b73319d20cd73 (MD5) / Made available in DSpace on 2018-09-27T14:19:44Z (GMT). No. of bitstreams: 1 KELLEN ROCHA.pdf: 1430079 bytes, checksum: ba3882603d46f2a9824b73319d20cd73 (MD5) Previous issue date: 2017-07-14 / A doença de Alzheimer (DA) é uma desordem neurodegenerativa crônica caracterizada clinicamente pela perda progressiva de função cognitiva, distúrbios neuropsiquiátricos e comportamentais. Patologicamente esta doença caracteriza-se pelo acúmulo anormal do peptídeo β-amilóide (Aβ) no córtex e no hipocampo, emaranhados neurofibrilares intracelulares formados por tau hiperfosforilada, disfunção progressiva sináptica e, posteriormente perda neuronal. As opções terapêuticas disponíveis melhoram os sintomas, mas não impedem a progressão da doença, portanto, ainda está faltando uma estratégia terapêutica efetiva para DA. Há estudos relacionados à utilização de terapia epigenética para o tratamento da DA, a terapêutica mais desenvolvida é a que envolve a classe dos inibidores das deacetilases (HDACs). Assim, este trabalho tem por objetivo investigar o efeito protetor do inibidor da HDAC ácido hidroxâmico de suberoilanilida (SAHA) em um modelo de DA em camundongos. Para isso, foram utilizados 50 camundongos Swiss adultos, pesando entre 30-35 g, divididos em dois experimentos. No primeiro, os camundongos foram divididos em 6 grupos que receberam uma injeção de Aβ1-42 via intracerebroventricular (i.c.v.) no início da experiência (exceto o grupo Sham que foi utilizado como controle) para investigar a atividade das histonas   acetiltransferase (HATs) e HDAC, determinação dos níveis do fator neurotrófico derivado do cérebro (BDNF), expressão do mRNA de BDNF e modulação da via (cAMP/PKA/CREB) em uma curva de tempo (6 horas, 1, 3, 7 e 21 dias). Ao final de cada tempo, os animais foram submetidos ao teste cognitivo e foram eutanasiados. O córtex pré-frontal e o hipocampo foram removidos para posteriores análises. No segundo experimento, os camundongos foram dividos em 4 grupos: Grupo Controle (sham+veículo); Grupo Aβ1-42 (Aβ1-42 + veículo); Grupo SAHA (25 mg/kg, via intraperitoneal) (sham + SAHA); Grupo Interação (Aβ1-42 + SAHA). O peptídeo Aβ1-42 ou o veículo foram infundidos por injeção i.c.v. e, um dia depois, iniciou-se o tratamento, por via i.p., durante 21 dias. Ao final do experimento os animais foram submetidos ao teste cognitivo, eutanásiados para retirada das estruturas cerebrais. As amostras foram utilizadas para a determinação dos níveis de BDNF, expressão do mRNA de BDNF, atividade enzimática das histonas (HDAC e HATs) e regulação da via cAMP/PKA/CREB. O presente estudo observou deficiências significativas causadas pela Aβ1-42 na memória (Labirinto Aquático de Morris), bem como causou desequilíbrio das enzimas HAT/HDAC, redução de cAMP, PKA e CREB e BDNF no córtex pré-frontal e hipocampo de camundongos. A inibição de HDAC, com SAHA demostrou neuroproteção nas alterações comportamentais e neuroquímicas induzidas por Aβ1-42. Estes dados mostram que a acetilação através da inibição do HDAC, desempenha um papel fundamental na mediação da memória e demonstra que SAHA poderá ser uma ferramenta médica promissora na abordagem terapêutica para o tratamento da DA. / Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized clinically by the progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Pathologically this disease is characterized by the abnormal accumulation of β-amyloid peptide (Aβ) in the cortex and hippocampus, intracellular neurofibrillary tangles formed by hyperphosphorylated tau, progressive synaptic dysfunction and, later, neuronal loss. The available therapeutic options improve the symptoms, but they do not prevent the progression of the disease, therefore, an effective therapeutic strategy for AD is still lacking. There are studies related to the use of epigenetic therapy for the treatment of AD, the most developed therapy is that involving the class of deacetylase inhibitors (HDACs). Thus, this work aims to investigate the protective effect of the HDAC inhibitor hydroxamic acid suberoilanilide (SAHA) in an AD model in mice. For this, 50 Swiss adult mice weighing between 30-35 g were used, divided in two experiments. In the first, the mice were divided into 6 groups that received an injection of Aβ1-42 via the intracerebroventricular (i.c.v.) at the beginning of the experiment (except the Sham group that was used as control) to investigate histone activity acetyltransferase (HATs) and HDAC, determination of brain derived neurotrophic factor (BDNF) levels, expression of BDNF mRNA and modulation of the pathway (cAMP / PKA / CREB) in a time curve (6 hours, 1, 3, 7 and 21 days). At the end of each time, the animals were submitted to the cognitive test and were euthanized. The prefrontal cortex and hippocampus were removed for further analysis. In the second experiment, the mice were divided into 4 groups: Control Group (sham + vehicle); Group Aβ1-42 (Aβ1-42 + vehicle); SAHA group (25 mg / kg, intraperitoneal route) (sham + SAHA); Interaction Group (Aβ1-42 + SAHA). The Aβ1-42 peptide or vehicle was infused by i.c.v. and one day later the treatment was started i.p. for 21 days. At the end of the experiment the animals were submitted to the cognitive test, euthanasia for removal of the cerebral structures. The samples were used for the determination of BDNF levels, expression of BDNF mRNA, histone enzymatic activity (HDAC and HATs) and regulation of the cAMP / PKA / CREB pathway. The present study observed significant deficiencies caused by Aβ1-42 in memory (Morris Aquatic Labyrinth), as well as caused imbalance of HAT / HDAC enzymes, cAMP, PKA and CREB and BDNF reduction in the prefrontal cortex and hippocampus of mice. Inhibition of HDAC with SAHA demonstrated neuroprotection in behavioral and neurochemical changes induced by Aβ1-42. These data show that acetylation through inhibition of HDAC plays a key role in memory mediation and demonstrates that SAHA may be a promising medical tool in the therapeutic approach to AD.

Esta tese de doutorado busca fazer uma articulação entre conceitos da metapsicologia freudiana e sintomas da demência de tipo Alzheimer, como descritos pela neuropsicologia. A pesquisa levou a estudar a relação do idoso com seu corpo, durante o processo de envelhecimento, assim como o desenvolvimento do conceito de narcisismo por Freud e a implicação da estruturação deste para o surgimento das demências. Num segundo momento, seguindo os passos já trilhados por autores que levantaram a hipótese da relação entre o aparecimento do sintoma de perda de memória e a dificuldade na elaboração dos lutos, levantou-se a hipótese do sintoma de perda de memória como um mecanismo de defesa. A história subjetiva em relação ao complexo de castração define a maneira como o sujeito poderá lidar com a castração imposta pela aproximação do fim do Eu. Por fim, propôs-se uma leitura psicanalítica para as mudanças experimentadas pelo sujeito, desde o diagnóstico da doença de Alzheimer até o estágio avançado da doença. Nesse percurso, fica claro que, na fase inicial, o Supra Eu encontra-se abalado; na fase intermediária, são as funções do Eu que são atingidas até o ponto de nos encontrarmos diante de um sujeito sem um funcionamento egoico. É possível supor que, sem a possibilidade da sublimação ou da simbolização, as pulsões, sem representações que possam enlaçá-las, invadem o aparelho psíquico e o corpo do idoso, o qual já não se reconhece mais como um sujeito. Essa desintegração do Eu, à luz da metapsicologia, poderia ser compreendida como uma forma de mecanismo de defesa que protegeria o sujeito de entrar em contato com uma dor maior, ligada a uma história de lutos não elaborados e de traumas que seriam reatualizados no contato com os desafios do processo de envelhecimento / This doctoral thesis seeks to articulate concepts of Freudian metapsychology and the symptoms of Alzheimer\'s dementia as described by neuropsychology. The research led us to study the relationship that the elderly develop with their body during the aging process as well as the development of the concept of narcissism by Freud and the implication of the structure of this to the onset of dementia. In a second chapter, following the steps already taken by authors who raised the hypothesis of the relationship between the appearance of the symptom of memory loss and the difficulty in the elaboration of mourning, we hypothesized that the memory loss symptom can be understood as a defense mechanism. The subjective history of the castration complex defines the way in which the subject can deal with the castration imposed by the approximation of the end of life. Finally, we propose a psychoanalytic reading for the changes experienced by the subject from the diagnosis of Alzheimer\'s disease to the advanced stage of the disease. In this course, it is clear that in the initial phase, the Superego is shaken, in the intermediate phase, the functions of the ego are affected to the point of being faced with a subject without an egoic functioning. It is possible to suppose that without the possibility of sublimation or symbolization, the drives, without representations that can entail them, invade the psychic apparatus and the body of the elder who no longer recognizes himself as a subject. This disintegration of the ego, in the light of metapsychology, could be understood as a form of defense mechanism that would protect the subject from coming into contact with a greater pain, linked to a history of unprocessed mourning and traumas that would be awoken by the challenges of the aging process

O Mal de Alzheimer (MA) foi caracterizado pela primeira vez em 1907 pelo neuropatologista alemão Alois Alzheimer, tendo como sintomas clínicos disfunções cognitivas, fisiológicas, comportamentais, perda de memória, e eventualmente incontinência, demência, acamação e morte. É uma doença neurodegenerativa do sistema nervoso central que costuma afetar, principalmente, indivíduos em faixa etária mais avançada. Este mal é caracterizado microscopicamente pela presença de placas amilóides, que são acúmulos da proteína betaamilóide inter-neurônios, e emaranhados neurofibrilares, formados predominantemente por formas altamente fosforiladas de uma proteína associada aos microtúbulos, Tau, as quais formam massas emaranhadas que consomem o corpo celular neuronal, possivelmente levando à disfunção neuronal e finalmente à morte. MAPK p38? tem sido implicada em dois eventos associados ao MA, fosforilação da Tau e inflamação. MAPK p38? é ativada por uma via de fosforilação dupla em Thr180 e Tyr182. O planejamento de fármacos inibidores de p38? é principalmente focado em pequenas moléculas que competem pelo sítio catalítico do ATP. Aqui, nós utilizamos diferentes técnicas de modelagem molecular e planejamento racional baseado em estrutura e ligantes, tendo como base os inibidores da MAPK p38? descritos na literatura, além das estruturas depositadas no PDB. Como resultado das diferentes abordagens de triagens virtuais utilizadas neste trabalho, tais como \"docking\", farmacóforo, dinâmica molecular, campos de interação molecular, predição de atividade e toxicidade, cálculo de propriedades farmacocinéticas e físico-químicas, foi selecionado um total de 14 compostos que atendem aos critérios adotados de baixa ou nenhuma toxicidade potencial, bom perfil farmacoterapêutico predito, atividades calculadas em valores comparáveis aos obtidos para os compostos de referência, além da manutenção das principais interações observadas para os inibidores mais potentes. Estes compostos podem ser adquiridos para estudos de inibição in vitro frente à enzima MAPK p38?, contribuindo assim na busca de um potencial candidato à fármaco no tratamento do Mal de Alzheimer. / Alzheimer\'s disease (AD) was first characterized in 1907 by the German neuropathologist Alois Alzheimer, whose clinical symptoms includes cognitive, physiological and behavioral dysfunctions, memory loss, eventually incontinence, dementia, and death. It is a neurodegenerative disease of the central nervous system that usually affects individuals group in older age. This is characterized microscopically by the presence of amyloid plaques, which are accumulations of beta-amyloid protein inter-neurons, and neurofibrillary tangles formed predominantly by highly phosphorylated forms of the microtubule-associated protein, tau, which form tangled masses that consume neuronal cell body, possibly leading to neuronal dysfunction and ultimately death. p38? MAPK has been implicated in both events associated with AD, tau phosphorylation and inflammation. p38? MAPK pathway is activated by a dual phosphorylation at Thr180 and Tyr182 residues. The drug design of p38? MAPK inhibitors is mainly focused on small molecules that compete for ATP in the catalytic site. Here, we used different techniques of molecular modeling based on p38? MAPK structure deposited in the PDB and its inhibitors described in the literature. As a result of different virtual screening approaches used in this work, such as \"docking\", pharmacophore, molecular dynamics, molecular interaction fields, activity and toxicity predictions assays, pharmacokinetic properties and physicochemical, was selected a total of 14 compounds that meet these criteria of low or no toxicity potential, good pharmacotherapeutic profile, predicted activities calculated values comparable to those obtained for the reference compounds, while maintaining the main interactions observed for the most potent inhibitors. These compounds should be acquired for in vitro inhibition studies against the enzyme p38? MAPK, thereby helping in the search of a potential drug candidate for the treatment of Alzheimer\'s disease.

"Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to dementia in adults. The mechanism of neurodegeneration is thought to involve the extracellular production of a highly toxic A-beta peptide that engages cell surface receptors to induce cellular oxidative stress and apoptosis, but the signal transduction pathways that lead to A-beta induced cell death are unknown. We previously showed that a human ependymin neurotrophic peptide mimetic (hEPN-1) can promote cell survival in an in vitro AD model system. This initial observation was extended in this thesis by investigating the mechanism of A-beta induced apoptosis and hEPN-1 induced survival. Immunoblots were used to assay the total cellular levels of specific caspase proteins. The results show that A-beta induced apoptosis uses an extrinsic caspase pathway involving caspases-2 and -3, and that hEPN-1 treatment can reduce those caspase levels. A caspase activity assay showed that A-beta increased caspase-3/7 activity, while hEPN-1 treatment lowered it. Moreover, in vivo studies with AD transgenic mice showed that hEPN-1 treatment increased antioxidative superoxide dismutase levels in brain. Thus, hEPN-1 holds potential as a therapeutic to treat the underlying neurodegenerative cause of AD, not merely its symptoms as with other currently approved AD drugs."

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. The most accepted hypothesis for the cause of this disease is the amyloid cascade hypothesis, which postulates that the formation of extracellular neurotoxic amyloid-beta binds specific receptors on the surface of neuronal and glial cells to increase cell stress leading to cell death. Our laboratory previously showed that treatment of cultured human SHSY neuronal cells with amyloid beta increases the cellular levels of two key components (caspases-2 and -3) of the extrinsic apoptotic pathway, leading to cell death. The amyloid beta induced caspase elevation was blocked by simultaneously treating the cells with a short mimetic of human ependymin neurotrophic factor, hEPN-1, and the hEPN-1 treatment also blocked cell death. This thesis extends the AD investigation to show that treatment of SHSY cells with amyloid beta may also activate an intrinsic apoptotic mitochondrial stress pathway (assaying caspase-9 as a marker enzyme), and that hEPN-1 treatment significantly lowers this activation. In addition, our laboratory previously showed that treating SHSY cells with amyloid beta increases TUNEL staining, an assay for DNA fragmentation (a hallmark of end stage of apoptosis, and a different apoptotic marker than caspase activation). Treatment with hEPN-1 simultaneously with the amyloid beta, or 6 hrs post amyloid beta, significantly lowered the amyloid beta induced TUNEL signal. This thesis extended the earlier TUNEL experiments to show that hEPN-1 treatment can significantly lower the amyloid beta induced TUNEL staining even when added 18 hrs post amyloid beta. With respect to caspase-8, an initiator caspase in the extrinsic pathway, immunoblot assays of brain lysates from 8 month old transgenic AD mice showed that a 2 week oral delivery of hEPN-1 (conjugated to a carrier to deliver it across the blood brain barrier) significantly lowered caspase-8 levels. Finally, an assay of cellular inhibitors of apoptosis (cIAP) showed a significant increase in their cellular levels in SHSY cells, and in transgenic AD mice treated with hEPN-1, showing for the first time that hEPN-1 may aid cell survival by upregulating proteins known to directly bind specific caspases to block their activity leading to their degradation. The cIAP upregulation occurred in the presence or absence of amyloid beta, indicating that hEPN-1 likely does not block cell death by directly interfering with the interaction of amyloid beta with its cell surface receptors, but instead hEPN-1 may activate an independent cell survival signal transduction pathway in neuronal cells.

Les maladies à prions sont des pathologies neurodégénératives d’évolution fatale, transmissibles, pour lesquelles aucun traitement efficace n’existe. Elles associent sur le plan neuropathologique une spongiose, une gliose astrocytaire, une perte neuronale, et une accumulation de la forme anormalement repliée (PrPsc) de la protéine prion cellulaire codée par l’hôte. Certaines formes de cette maladie sont associées à une tauopathie et présentent des lésions neuropathologiques similaires à celles retrouvées dans la maladie d’Alzheimer (MA).Nous avons utilisé un modèle de cultures primaires de neurones afin d’explorer d’une part la relation entre la protéine prion et la physiopathologie de la protéine tau, et d’étudier d’autre part la propagation de souches humaines et l’effet de composés anti-prions sur cette propagation. Nos résultats indiquent que l’hyperphosphorylation de tau en réponse à l’exposition de PrP recombinantes est mutation dépendante, conformation dépendante, partiellement dépendante de la PrPc et est médiée par la kinase PDK1. Nous avons aussi démontré pour la première fois que la propagation d’isolats humains de maladie de Creutzfeldt-Jakob est possible dans un modèle in vitro et permet une évaluation rapide de l’efficacité de composés anti-prions, confirmée in vivo. Ces travaux ont permis de mieux caractériser la relation protéine amyloïde-physiopathologie de tau, d’ouvrir des perspectives de recherche dans la compréhension des mécanismes impliqués dans la MA, et d’apporter un modèle unique permettant d’évaluer rapidement les effets de molécules anti-prions vis-à-vis des souches les plus pertinentes, dans une stratégie de repositionnement thérapeutique. / Prion diseases are fatal transmissible neurodegenerative disorders, with no effective treatment. Brain lesions include neuronal vacuolization, astrogliosis, neuronal loss and the accumulation of PrPSc, an abnormal isoform of the host-encoded cellular prion protein (PrPc). Some forms of prion diseases are associated with tau fibrillar pathology similar to that observed in Alzheimer’s disease except that Abeta peptides are replaced by PrPsc. Here we used a primary neuronal cultures to first explore the interplay between the formation of prion protein assemblies and the occurrence of tau pathology, and secondly to evaluate in vitro human strain propagation and the efficiency of some antiprion compounds towards human prions. We showed that tau hyperphosphorylation in response to recombinant PrPs exposition was mutation-dependent, conformation-dependent and varied with the PrPc expression level of exposed neurons. This effect was mediated by PDK1 kinase. We also demonstrated for the first time that human prion isolates could propagate in an in vitro model. This model was also useful to evaluate the efficacy of antiprion compounds that was further validated in vivo. Our results help us to better understand the amyloid protein-tau physiopathology interplay and provide a useful and unique tool for fast evaluation of therapeutic compounds active against human prion strains in a repositioning strategy in such rare but devastating diseases.

Orientador: Florindo Stella / Banca: Geni de Araujo Costa / Banca: José Luiz Riani Costa / Resumo: A doença de Alzheimer (DA) é caracterizada por alterações cognitivas, psicológicas, comportamentais, funcionais e metabólicas. Dentre estas alterações, destacamos os sintomas depressivos e as alterações metabólicas. A prática de atividade física tem se mostrado uma importante ferramenta não farmacológica que auxilia no tratamento da DA. Este estudo foi dividido em duas partes. O estudo 1 teve como objetivo caracterizar o nível de atividade física; analisar se há associação do nível de atividade física e sintomas depressivos e entre nível de atividade física e variáveis metabólicas em pacientes com DA. Participaram deste estudo 37 pacientes nos estágios leve e moderado da DA. Os sintomas depressivos foram avaliados pela Escala de Cornell para Depressão em Demência e pela Escala Geriátrica de Depressão; o nível de atividade física foi avaliado pelo Questionário Baecke Modificado para Idosos. Para mensurar as variáveis metabólicas (colesterol total, HDL, LDL, VLDL, triglicérides, glicemia e homocisteina sérica) os pacientes foram encaminhados a um laboratório especializado. Para traçar o perfil cognitivo global utilizamos o Mini-Exame do Estado Mental e o Montréal Cognitive Assessment. Para análise dos dados utilizamos o teste de Shapiro Wilk para verificar a distribuição dos dados. O teste de correlação de Spearman foi utilizado para verificar possíveis relações entre as variáveis analisadas. Os testes de t student e U Mann Whitney foram utilizados para comparar os grupos com maior e menor nível de atividade física. Admitiu-se nível de significância de 5% para todas as análises. O nível de atividade física encontrado foi considerado baixo. Pacientes mais ativos apresentam menos sintomas depressivos e menor... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Alzheimer's disease (AD) is characterized by cognitive, psychological, behavioral, functional and metabolic. Among these changes, we can detach the depressive symptoms and metabolic changes. The practice of physical activity has proved to be an important tool as a non-pharmacological treatment of these changes. This study was divided into two parts. The study 1 aimed to characterize the level of physical activity, analyze whether there is an association of physical activity level and depressive symptoms and between physical activity level and metabolic variables in patients with AD. The study included 37 patients in mild and moderate stages of DA. Depressive symptoms were assessed by the Cornell Scale for Depression in Dementia and the Geriatric Depression Scale, and the level of physical activity was assessed by the Baecke Questionnaire Modified for the Elderly. To measure the metabolic variables (total cholesterol, HDL, LDL, VLDL, triglycerides, blood glucose and serum homocysteine) patients were referred to a specialized laboratory. To characterize the overall cognitive profile, it was used the Mini-Mental State Examination and the Montréal Cognitive Assessment. For data analysis was used the Shapiro Wilk test to verify the data distribution. The Spearman correlation test was used to verify possible relations between the variables. The Student's t test and U Mann Whitney test was used to compare the groups with higher and lower levels of physical activity. The level of significance was set at 5% for all analyses. The level of physical activity was found to be low. Patients that were more active showed less depressive symptoms and lower serum homocysteine concentration. Relationships were found between physical activity level and depressive symptoms according to the patient response; between physical activity level... (Complete abstract click electronic access below) / Mestre

Le présent travail de thèse par articles visait à apporter sa contribution, d’une part à la compréhension des relations entre mouvements oculaires et vieillissement cognitif normal et pathologique, d’autre part à la caractérisation des modifications oculomotrices spécifiques à la maladie d’Alzheimer et à la dépression, deux pathologies parfois cliniquement difficiles à discriminer chez la personne âgée. À travers une série de quatre articles et une expérience non publiée, nous avons examiné les relations entre le déclin des capacités de contrôle cognitif associé au vieillissement normal et les modifications des paramètres des saccades oculaires liées à l’âge. Par ailleurs, nous avons également étudié précisément les caractéristiques de différents paramètres des saccades et leurs liens avec l’altération du contrôle cognitif dans la maladie d’Alzheimer. La comparaison directe des performances oculomotrices de patients atteints de la maladie d’Alzheimer et de patients âgés atteints de dépression a permis de différencier des caractéristiques oculomotrices spécifiques à la maladie d’Alzheimer de celles spécifiques à la dépression du sujet âgé. Enfin, nous avons pu mettre en évidence la spécificité de l’analyse visuelle des informations émotionnelles des visages chez des patients âgés souffrant de dépression.Dans l’ensemble, ces travaux ont montré une influence du déclin cognitif lié à l’âge, mais aussi de la dépression et de la maladie d’Alzheimer sur les performances oculomotrices. Le ralentissement du traitement de l’information semble avoir un impact sur les paramètres des saccades sur toutes les tâches proposées. La latence et le nombre de saccades erronées ont pu être associés aux capacités d’inhibition. Le nombre et le temps de correction des saccades corrigées étaient plutôt liés aux capacités de surveillance (monitoring) et de flexibilité cognitive. Les capacités de correction des saccades erronées dans la dépression étaient similaires à celles du vieillissement normal, mais altérées dans la maladie d’Alzheimer. La latence des saccades était par contre plus influencée par la dépression que par la maladie d’Alzheimer. De plus, le traitement des stimuli émotionnels a révélé des stratégies particulières chez les patients âgés atteints de dépression – un évitement des caractéristiques émotionnelles des visages, excepté pour la joie – qui pourraient être différentes de l’altération de la recherche visuelle retrouvée dans la maladie d’Alzheimer par des études antérieures. Que ce soit au travers des tâches de saccades ou d’exploration visuelle, les mouvements oculaires peuvent refléter les processus de contrôle cognitif et permettre de différencier la dépression de maladie d’Alzheimer. / This doctoral dissertation aimed at better characterizing the relations between eye movements and normal and pathological cognitive ageing on the one hand, and the oculomotor modifications related to Alzheimer's disease and depression – two pathologies sometimes clinically difficult to discriminate in the elderly person — on the other hand. Through a series of five experiments, we examined the relations between the decline of the cognitive control capacities associated with normal ageing and the age-related modifications of the ocular saccade parameters. In addition, we also precisely studied the characteristics of various saccade parameters and their relations with the deterioration of cognitive control, present in the Alzheimer's disease. The direct comparison of the oculomotor performances of patients suffering from the Alzheimer's disease and elderly patients suffering from depression allowed us to differentiate the oculomotor characteristics specific to the Alzheimer's disease from those specific to the depression. Lastly, we highlighted the specificity of the visual process of emotional faces among elderly patients suffering from depression.Globally, this work showed an influence of the cognitive decline related to the age, but also of the depression and Alzheimer's disease on the oculomotor performances. The information processing slowing seems to have an impact on the parameters of all the saccadic tasks. The latency and the number of erroneous saccades were associated with the inhibition capacities. The number and the time of correction of corrected saccades were rather related to the monitoring and flexibility abilities. The capacities of correction of erroneous saccades in depression were similar to those of normal ageing, but impaired in Alzheimer's disease. On the other hand, the saccade latency appears to be more impacted by depression than by Alzheimer's disease. Moreover, the emotional face processing revealed the presence of particular strategies among elderly patients suffering from depression – avoidance of the emotional facial features, except for happy faces – and which could be different from the alteration of the visual search previously found in Alzheimer's disease. Whether it be in saccade tasks or in visual exploration tasks, eye movements can reflect cognitive control and enable us to differentiate depression from Alzheimer’s disease.