Telomere, the ends of chromosomes, consists of simple hexameric repeats. In human, TTAGGG repeat is found at the ends of all chromosomes. Telomeres progressively shorten with age in somatic cells, because the insufficient telomerase activity fails to compensate the progressive telomeric erosion. Thus, the reduction of telomeric length in senescent cells is believed to result from active cell division that erodes chromosomal termini. The telomere length supposed to have been an evaluation tool for aging in human. Schizophrenia is a thought, perception disorder, generally regarded as an illness with onset in late adolescence or early adult life with a prevalence rate of 1%. Although the long-term course of schizophrenia shows great heterogeneity among patients, a significant number of patients experience very poor outcomes, shows severe cognitive impairment that is suggestive of a progressive neurodegenerative disorder. The aim of this study is to explore the relationship between neurodegenerative process and telomere length in schizophrenic patients. The latency of P300 event-related potentials is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of aging process. This study is separated as two parts: first part, using the event-related potentials P300 latency as a tool to evaluate the cognitive dysfunction and aging process in schizophrenics. One hundred and fifty three long-term hospitalization chronic schizophrenics were recruited as the experimental group of this research, including 44 male and 109 female patients with mean age of 38.4 years. These patients were divided into 2 groups according to the different responses to treatment, global assessment functional scale (GAF): 91 with good response to treatment; 62 with poor response to treatment. The normal control group included 101 normal people, male 37 and female 76, with mean age of 38.1 years. The event-related potentials was elicited by auditory oddball paradigm. The P300 latency prolonged in these two schizophrenic patients. The longest P300 latency was found in the poor response schizophrenic group. The shortest P300 latency was found in the normal group. Linear regression coefficients were computed to determine the slope of component P300 latency on age and other factors. The slope of P300 latency on age in normal control group is 1.2 ms/y. In schizophrenic groups, not only the age, but the GAF as the most contributing factors in the neurodegenerative process. Second part, the subjects were selected from part one, 48 chronic schizophrenia whose mean age was 37.9 years and 48 age-, handedness-, and gender-matched normal control subjects. The schizophrenic patients were divided into 2 groups according to the different responses to treatment: 34 with good response to treatment; 14 with poor response to treatment. The telomere length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. The shortest TRF length was found in the poor response schizophrenic group. There was no difference between the good response schizophrenic group and normal control group. TRF length in peripheral leukocytes obtained from normal control group decreased by approximately 89bP per year. In schizophrenic groups, the TRF length was found that not the age, but the age onset and GAF as the most contributing factors in linear regression model. This study shows that the poor response schizophrenic patients have the most rapid neurodegenerative process in P300 latency and TRF length evaluation. It implicates the homogeneous group, and can be considered as the kraepelinian schizophrenics, very poor outcome group.

Autism is a neurodevelopmental disorder featuring severe social and communicative deficits. Cognitive impenetrability is the inability of systems to be affected by an individual’s beliefs and desires. Individuals with autism have delayed performance on "mindreading" tasks. Mindreading is the interpretation of others which enables successful social interactions. This task performance is not correlated with "everyday" social function in autism. These deficits are in contrast with general intelligence and reasoning abilities within the normal range, resistant to cognitive behavioral training, and partially attributable to atypical social predispositions. This suggests individuals with autism perform social tasks differently than typicals. I argue that this mindreading deficit is cognitively impenetrable, then position this deficit within a theoretical framework, enactivism, emphasizing cognitive embodiment and inseparability of social comprehension and action. This framework helps explain the cognitive impenetrability of these social deficits by "locating" failure to penetrate in individuals' failure to properly interact with the environment.

Depressive symptoms are very common among people with neurocognitive disorder. The comorbidity of both diseases and the overlap of their symptoms complicates correct diagnosis and thus also the initiation of a correct treatment. The instruments of depression measuring in seniors with a severe cognitive deficit are also a discussed issue. The subject of the theoretical part is to describe the issue of depression and cognitive disorders in the old age with a focus on Alzheimer's disease, which is the most common mental disorder in the elderly together with depression. The goal of the empirical part of the thesis is to research based on the interviews with seniors if the most frequently used method of depression measuring in the elderly, Geriatric Depression Scale (GDS), is a suitable measuring instrument also in seniors with a cognitive deficit and further examine how these seniors actually experience the individual mood qualities which are the subjects of items in GDS. Forty seniors with a various degree of cognitive deficit participated in the research. The study results showed that the questionnaire is usable for seniors with a mild cognitive impairment and mild dementia. To detect the border of the cognitive deficit, below which it is not suitable to use the depression measuring method GDS, a...

Crianças são mais sensíveis aos efeitos adversos causados por contaminantes ambientais, tais como os metais, do que os adultos. Dentre esses efeitos adversos, estão os danos ao sistema nervoso central e inibição da enzima δ-aminolevulinato desidratase (ALA-D). Neste trabalho, as concentrações de alguns metais (Al, Pb, Cd, As, Hg, Cr, Mn e Fe) foram quantificadas em amostras de sangue total, soro e cabelo de crianças provenientes de uma área rural e de uma área urbana. Esses elementos também foram quantificados em amostras de água das residências das crianças. A função cognitiva foi avaliada através da aplicação do Teste Matrizes Progressivas Coloridas de Raven. A atividade da enzima ALA-D e o índice de reativação da enzima (ALA-RE) com DTT e com ZnCl2 foram avaliados. As crianças da área rural demonstraram menor desempenho cognitivo no Teste de Raven do que as crianças da área urbana (p<0,001). Níveis sanguíneos de Cr e Hg foram negativamente associados aos escores de QI (p<0,005). Além disso, os escores de QI foram negativamente associados com os níveis de Mn e Fe no cabelo (p<0,01). Adicionalmente, correlações de Spearman foram observadas entre: Mn no cabelo vs. Mn na água (p<0,001); Fe no cabelo vs. Fe na água (p<0,05) e Fe no sangue total vs. Fe na água (p<0,001). A atividade da enzima ALA-D foi significativamente diminuída nas crianças da área rural em relação às crianças da área urbana (p<0,05), bem como a ALA-RE com DTT e ZnCl2 foi significativamente aumentada nas crianças da área rural em comparação com as crianças da área urbana (p<0,005). Adicionalmente, a inibição da ALA-D foi correlacionada com os níveis sanguíneos de Cr (p<0,05) e a ALA-RE com DTT foi associada com os níveis sanguíneos de Cr (p<0,001) e Hg (p<0,001). De forma semelhante, a ALA-RE com ZnCl2 foi também correlacionada com níveis sanguíneos de Cr e Hg (p<0,05). Neste estudo foi possível observar déficit na função cognitiva e inibição da ALA-D associados à exposição a alguns metais em crianças da área rural. Além disso, os resultados indicaram a água como uma provável fonte de contaminação a metais. / Children are more sensitive to the adverse effects caused by environmental contaminants, such as metals, than adults. Among these adverse effects, there are the damage to nervous system central and inhibition of the enzyme δ-aminolevulinate dehydratase (ALA-D). In this study, the concentrations of some metals (Al, Pb, Cd, As, Hg, Cr, Mn and Fe) were quantified in whole blood, serum and hair of children from rural and urban areas. These elements were measured on samples of drinking water from household’s children. The cognitive function was evaluated by the Raven’s Colored Progressive Matrices Test. The activity of the ALA-D and the rate of reactivation of the enzyme (ALA-RE) with DTT and ZnCl2 were evaluated. Children from rural area had lower performance on the Raven’s Test than children from urban area (p<0.001). The Cr and Hg blood levels were negatively associated with percentile IQ scores (p<0.05). Moreover, the IQ scores were negatively associated with Mn and Fe in hair (p<0.01). Additionally, Spearman’s correlations were found between: Mn in hair vs. Mn in drinking water (p<0.001); Fe in hair vs. Fe in drinking water (p<0.05) and Fe in whole blood vs. Fe in drinking water (p<0.001). The activity of ALA-D was significantly decreased in children from rural area when compared with children from urban area (p<0.05) and the ALA-RE with DTT and ZnCl2 was significantly increased in children from rural area compared with children from urban area (p<0.005). Additionally, the ALA-D inhibition was correlated with Cr in blood (p<0.05) and ALA-RE with DTT was associated with blood levels of Cr and Hg (p<0.001). Similarly, ALA-RE with ZnCl2 was also correlated with blood levels of Cr and Hg (p<0.05). In this study it was revealed cognitive deficit and ALA-D inhibition associated with exposure to some metals in children from a rural area. Moreover, the results indicated the drinking water as a possible source of contamination to metals.

Crianças são mais sensíveis aos efeitos adversos causados por contaminantes ambientais, tais como os metais, do que os adultos. Dentre esses efeitos adversos, estão os danos ao sistema nervoso central e inibição da enzima δ-aminolevulinato desidratase (ALA-D). Neste trabalho, as concentrações de alguns metais (Al, Pb, Cd, As, Hg, Cr, Mn e Fe) foram quantificadas em amostras de sangue total, soro e cabelo de crianças provenientes de uma área rural e de uma área urbana. Esses elementos também foram quantificados em amostras de água das residências das crianças. A função cognitiva foi avaliada através da aplicação do Teste Matrizes Progressivas Coloridas de Raven. A atividade da enzima ALA-D e o índice de reativação da enzima (ALA-RE) com DTT e com ZnCl2 foram avaliados. As crianças da área rural demonstraram menor desempenho cognitivo no Teste de Raven do que as crianças da área urbana (p<0,001). Níveis sanguíneos de Cr e Hg foram negativamente associados aos escores de QI (p<0,005). Além disso, os escores de QI foram negativamente associados com os níveis de Mn e Fe no cabelo (p<0,01). Adicionalmente, correlações de Spearman foram observadas entre: Mn no cabelo vs. Mn na água (p<0,001); Fe no cabelo vs. Fe na água (p<0,05) e Fe no sangue total vs. Fe na água (p<0,001). A atividade da enzima ALA-D foi significativamente diminuída nas crianças da área rural em relação às crianças da área urbana (p<0,05), bem como a ALA-RE com DTT e ZnCl2 foi significativamente aumentada nas crianças da área rural em comparação com as crianças da área urbana (p<0,005). Adicionalmente, a inibição da ALA-D foi correlacionada com os níveis sanguíneos de Cr (p<0,05) e a ALA-RE com DTT foi associada com os níveis sanguíneos de Cr (p<0,001) e Hg (p<0,001). De forma semelhante, a ALA-RE com ZnCl2 foi também correlacionada com níveis sanguíneos de Cr e Hg (p<0,05). Neste estudo foi possível observar déficit na função cognitiva e inibição da ALA-D associados à exposição a alguns metais em crianças da área rural. Além disso, os resultados indicaram a água como uma provável fonte de contaminação a metais. / Children are more sensitive to the adverse effects caused by environmental contaminants, such as metals, than adults. Among these adverse effects, there are the damage to nervous system central and inhibition of the enzyme δ-aminolevulinate dehydratase (ALA-D). In this study, the concentrations of some metals (Al, Pb, Cd, As, Hg, Cr, Mn and Fe) were quantified in whole blood, serum and hair of children from rural and urban areas. These elements were measured on samples of drinking water from household’s children. The cognitive function was evaluated by the Raven’s Colored Progressive Matrices Test. The activity of the ALA-D and the rate of reactivation of the enzyme (ALA-RE) with DTT and ZnCl2 were evaluated. Children from rural area had lower performance on the Raven’s Test than children from urban area (p<0.001). The Cr and Hg blood levels were negatively associated with percentile IQ scores (p<0.05). Moreover, the IQ scores were negatively associated with Mn and Fe in hair (p<0.01). Additionally, Spearman’s correlations were found between: Mn in hair vs. Mn in drinking water (p<0.001); Fe in hair vs. Fe in drinking water (p<0.05) and Fe in whole blood vs. Fe in drinking water (p<0.001). The activity of ALA-D was significantly decreased in children from rural area when compared with children from urban area (p<0.05) and the ALA-RE with DTT and ZnCl2 was significantly increased in children from rural area compared with children from urban area (p<0.005). Additionally, the ALA-D inhibition was correlated with Cr in blood (p<0.05) and ALA-RE with DTT was associated with blood levels of Cr and Hg (p<0.001). Similarly, ALA-RE with ZnCl2 was also correlated with blood levels of Cr and Hg (p<0.05). In this study it was revealed cognitive deficit and ALA-D inhibition associated with exposure to some metals in children from a rural area. Moreover, the results indicated the drinking water as a possible source of contamination to metals.

Crianças são mais sensíveis aos efeitos adversos causados por contaminantes ambientais, tais como os metais, do que os adultos. Dentre esses efeitos adversos, estão os danos ao sistema nervoso central e inibição da enzima δ-aminolevulinato desidratase (ALA-D). Neste trabalho, as concentrações de alguns metais (Al, Pb, Cd, As, Hg, Cr, Mn e Fe) foram quantificadas em amostras de sangue total, soro e cabelo de crianças provenientes de uma área rural e de uma área urbana. Esses elementos também foram quantificados em amostras de água das residências das crianças. A função cognitiva foi avaliada através da aplicação do Teste Matrizes Progressivas Coloridas de Raven. A atividade da enzima ALA-D e o índice de reativação da enzima (ALA-RE) com DTT e com ZnCl2 foram avaliados. As crianças da área rural demonstraram menor desempenho cognitivo no Teste de Raven do que as crianças da área urbana (p<0,001). Níveis sanguíneos de Cr e Hg foram negativamente associados aos escores de QI (p<0,005). Além disso, os escores de QI foram negativamente associados com os níveis de Mn e Fe no cabelo (p<0,01). Adicionalmente, correlações de Spearman foram observadas entre: Mn no cabelo vs. Mn na água (p<0,001); Fe no cabelo vs. Fe na água (p<0,05) e Fe no sangue total vs. Fe na água (p<0,001). A atividade da enzima ALA-D foi significativamente diminuída nas crianças da área rural em relação às crianças da área urbana (p<0,05), bem como a ALA-RE com DTT e ZnCl2 foi significativamente aumentada nas crianças da área rural em comparação com as crianças da área urbana (p<0,005). Adicionalmente, a inibição da ALA-D foi correlacionada com os níveis sanguíneos de Cr (p<0,05) e a ALA-RE com DTT foi associada com os níveis sanguíneos de Cr (p<0,001) e Hg (p<0,001). De forma semelhante, a ALA-RE com ZnCl2 foi também correlacionada com níveis sanguíneos de Cr e Hg (p<0,05). Neste estudo foi possível observar déficit na função cognitiva e inibição da ALA-D associados à exposição a alguns metais em crianças da área rural. Além disso, os resultados indicaram a água como uma provável fonte de contaminação a metais. / Children are more sensitive to the adverse effects caused by environmental contaminants, such as metals, than adults. Among these adverse effects, there are the damage to nervous system central and inhibition of the enzyme δ-aminolevulinate dehydratase (ALA-D). In this study, the concentrations of some metals (Al, Pb, Cd, As, Hg, Cr, Mn and Fe) were quantified in whole blood, serum and hair of children from rural and urban areas. These elements were measured on samples of drinking water from household’s children. The cognitive function was evaluated by the Raven’s Colored Progressive Matrices Test. The activity of the ALA-D and the rate of reactivation of the enzyme (ALA-RE) with DTT and ZnCl2 were evaluated. Children from rural area had lower performance on the Raven’s Test than children from urban area (p<0.001). The Cr and Hg blood levels were negatively associated with percentile IQ scores (p<0.05). Moreover, the IQ scores were negatively associated with Mn and Fe in hair (p<0.01). Additionally, Spearman’s correlations were found between: Mn in hair vs. Mn in drinking water (p<0.001); Fe in hair vs. Fe in drinking water (p<0.05) and Fe in whole blood vs. Fe in drinking water (p<0.001). The activity of ALA-D was significantly decreased in children from rural area when compared with children from urban area (p<0.05) and the ALA-RE with DTT and ZnCl2 was significantly increased in children from rural area compared with children from urban area (p<0.005). Additionally, the ALA-D inhibition was correlated with Cr in blood (p<0.05) and ALA-RE with DTT was associated with blood levels of Cr and Hg (p<0.001). Similarly, ALA-RE with ZnCl2 was also correlated with blood levels of Cr and Hg (p<0.05). In this study it was revealed cognitive deficit and ALA-D inhibition associated with exposure to some metals in children from a rural area. Moreover, the results indicated the drinking water as a possible source of contamination to metals.

Topics of this diploma thesis are psychopathological consequences after craniocerebral trauma. This thesis focus on rising cognitive deficit after different brain damage. I solve rising of brain trauma and psychopathological deficits. I describe medical examination, which define diagnosis and individual form of rehabilitation. After that follows somatic and functional diabilities of central nervous system. The last chapter is about casuistry of young boy, who was injured in the crash. He had head injury with another psychopathological deficits.

La question de l'évaluation des aptitudes à la conduite constitue un enjeu important, tant en termes sécuritaires pour l'ensemble des usagers qu'en termes de qualité de vie pour les personnes dont les compétences subissent un déclin et voient leur autonomie menacée, comme les personnes atteintes de lésions cérébrales acquises. Classiquement, cette évaluation est assurée par une batterie de tests neuropsychologiques et une épreuve sur route. Cependant, ces outils présentent de nombreuses limites. Pour pallier ces limites, de plus en plus de praticiens et chercheurs se tournent vers des outils de simulation. Toutefois, les simulateurs ne font pas l'unanimité car il ne s'agit pas d'une mise en situation réelle. Le but de ce travail de thèse est de montrer l'apport du simulateur pour l'évaluation des compétences de conduite. Nous nous intéressons particulièrement à certains processus qui peuvent être déficitaires et avoir un impact important en conduite (attention sélective, attention partagée, anticipation, etc.). Pour cela, nous avons créé un protocole complet l'évaluation de la conduite, composé d'une batterie de tests neuropsychologiques, d'une épreuve de conduite sur route et d'une épreuve de conduite sur simulateur. Ce protocole a été proposé à des personnes victimes de lésions cérébrales,connues dans la littérature pour présenter des déficits dans les processus qui nous intéressaient. Nous voulions d'une part montrer que le simulateur de conduite est aussi discriminant que les deux autres évaluations pour estimer les compétences de conduite en confrontant les résultats aux différentes évaluations. D'autre part, nous souhaitions mettre en avant l'apport du simulateur pour l'étude des mécanismes déficitaires en montrant leur implication en conduite chez des populations présentant des déficits cognitifs comme les personnes cérébrolésées.Les résultats confirment que le simulateur de conduite peut permettre d'évaluer les compétences en conduite, comme les tests neuropsychologiques et l'évaluation sur route. En effet, lors du test de conduite sur simulateur les participants cérébrolésés étaient d’une part discriminés des participants contrôles. D’autre part, les résultats étaient cohérents entre les différentes évaluations : Les participants notés majoritairement déficitaires aux tests neuropsychologiques ou à l’épreuve sur route l’étaient également sur simulateur. Par ailleurs, le simulateur apporte un autre éclairage sur les déficits en conduite en apportant notamment des informations supplémentaires susceptibles d’expliquer la nature des déficits observés sur route (oculométrie, mesure des temps de réaction). Le simulateur permet ainsi d'étudier les principauxprocessus impliqués en conduite, dans une situation écologique. Le simulateur constitue donc un outil pertinent pour l’évaluation des déficits cognitifs et leurs répercussions sur l’activité de conduite. / The question of the driving skills assessment is an important issue, both in terms of security for all road users and in terms of life quality for people whose skills are decreasing and have their autonomy threatened, as brain-injured people. Usually, this assessment is performed by a neuropsychological tests battery and an on-road test. Nevertheless, these toolspresent many limitations. To overcome these limitations, more and more practitioners and researchers are looking around simulation tools. However, simulators are not welcomed unanimously because it is not a real-life situation. The purpose of this study is to show the contribution of the simulator in the assessment of the driving skills. We are particularly interested insome processes which may be impaired and may have a great issue in driving (selective attention, shared attention, anticipation, etc.). In that way, we created a complete assessment protocol of driving, consisting in a neuropsychological test battery, an on-road driving test, and a simulator driving test. This protocol was proposed to people suffering of brain damages, known in the literature to present deficits in the processes which interested us. We wanted on one hand to show that the driving simulator is also discriminating as the two other evaluations to estimate the driving skills, by confronting the results to the various evaluations. On the other hand, we wished to put forward the contribution of the simulator for the study of the impaired mechanisms by showing their implication in driving in populations presenting cognitive deficits as the brain-injured people.The results confirm that the simulator allow us to assess the driving skills, as well as neuropsychological tests and on-road evaluation. On one hand, during the driving test on simulator, the brain-injured participants were discriminated from the control one. On the other hand, the results were coherent between the various assessments: The participants who were mainly noted impaired in the neuropsychological tests or in the on-road driving test were also noted impaired on the simulator. Besides, the simulator gives another perspective on the deficits in driving by bringing in particular additional information susceptible to explain the nature of the deficits observed on road (eye-tracker, response time measures). The simulator so allows to study the main processes involved in driving, in an ecological situation. Thus, the simulator constitutes a relevant tool for assessing cognitive impairments and their repercussions on the driving activity.Moreover, it provides a new perspective on driving skills. It also help to study the main processes involved in driving, in ecological conditions. In particular, we could highlight some cognitive deficits in brain-injured people. The simulator is therefore a relevant tool

Cognitive impairment is commonly seen in the elderly population. It is unclear if cognitive deficit in heart failure (HF) patients is a primary factor for higher hospital readmission rates in this population. The Centers for Medicare and Medicaid Services have established strict guidelines for reimbursement on readmissions that occur within 30 days. It is imperative that organizations identify and rectify issues that impact readmissions. The aim of this project was to determine if there is a reduction in HF readmission after patients are screened for cognitive impairment. Orem's self-care model guided the project by providing a framework of inquiry regarding the impact of cognitive impairment on self-care deficits and the need for support for persons with heart failure. The project examined the hospital's 30-day readmission rate for the HF patients who received cognitive screening using a chi-square test; this analysis excluded HF patients who were not screened for cognitive impairment. Readmission rates for all patients during a 6-month period were examined. Two hundred sixty-eight patient records were reviewed; 48 patients were readmitted, and of those, 28 patients had completed the cognitive assessment, meeting the criteria for the project. The change in readmission rates was not significant (p = 0.196), suggesting that cognitive screening of patients is not associated with reduced readmission rates. Further research should examine the role of cognitive screening in addition to other resources on the 30-day readmission rate of HF patients. Social change will be improved as a result of the improved quality of life for HF patients and the reduced per-capita cost of health care in the United States.

no / Rationale Phencyclidine (PCP), a glutamate/N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to induce a range of symptoms similar to those of patients with schizophrenia, while d-amphetamine induces predominantly positive symptoms. Previous studies in our laboratory have shown that PCP can selectively impair the performance of an operant reversal-learning task in the rat. Furthermore, we found that the novel antipsychotic ziprasidone, but not the classical antipsychotic haloperidol, could prevent the PCP-induced deficit. Objectives The aim of the present study was to validate the model further using the atypical antipsychotic clozapine and then to investigate the effects of lamotrigine, a broad-spectrum anticonvulsant that is known to reduce glutamate release in vitro and is able to prevent ketamine-induced psychotic symptoms in healthy human volunteers. A further aim was to compare effects of PCP and d-amphetamine in the test and investigate the effects of the typical antipsychotic haloperidol against the latter. Methods Female hooded-Lister rats were food deprived and trained to respond for food in a reversal-learning paradigm. Results PCP at 1.5 mg/kg and 2.0 mg/kg and d-amphetamine at 0.5 mg/kg significantly and selectively impaired performance in the reversal phase of the task. The cognitive deficit induced by 1.5 mg/kg PCP was attenuated by prior administration of lamotrigine (20 mg/kg and 30 mg/kg) or clozapine (5 mg/kg), but not haloperidol (0.05 mg/kg). In direct contrast, haloperidol (0.05 mg/kg), but not lamotrigine (25 mg/kg) or clozapine (5 mg/kg), prevented a similar cognitive impairment produced by d-amphetamine (0.5 mg/kg). Conclusions Our findings provide further data to support the use of PCP-induced disruption of reversal learning in rodents to investigate novel antipsychotic drugs. The results also provide evidence for different mechanisms of PCP and d-amphetamine-induced disruption of performance in the test, and their different sensitivities to typical and atypical antipsychotic drugs.