Rationale Cognitive deficits are now recognised as a major symptom of schizophrenia with a number of studies reporting profound deficits in cognitive function in both chronic and first episode patients. Recent advances in cognitive remediation therapy have provided the opportunity for patients to improve their cognitive function and therefore improve their functional outcome. Aim The aim of the present study was to investigate cognitive deficits using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) in first episode psychosis and chronic schizophrenia patients. In the first episode population the effect of ethnicity on cognition was also examined. In the chronic schizophrenia study comparisons between severity of deficits with first episode psychosis patients were also made. The effects of cognitive remediation therapy were also examined in a sample of first episode patients. Methods A total of 35 patients and 30 healthy controls were recruited into the first episode study, 17 patients and 17 controls into the chronic schizophrenia study and 11 patients into the cognitive remediation study. The first episode psychosis patients were recruited from the Bradford and Airedale Early Intervention Service and the chronic patients from the Leeds Partnership NHS Foundation Trust. The control subjects were matched as closely as possible in terms of intelligence and demographics to the patient groups. The Wechsler Test of Adult Reading (WTAR) was used to estimate subjects pre-morbid IQ. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). All subjects who took part in the study completed a comprehensive battery of neuropsychological tests from the CANTAB®. Patients in the cognitive remediation study participated in group therapy sessions using X-cog®. Results There were no significant differences found between There were no significant differences found between patients and controls in relation to intelligence or demographics in all studies. The effect of ethnicity was shown to be not significant in the first episode study. Results show that patients performed significantly worse than controls across all iv cognitive domains tested in all studies. A correlation between negative symptoms and executive function was found in both first episode and chronic schizophrenia patients. Comparisons between first episode psychosis and chronic schizophrenia patients in cognition showed no significant differences, however significant differences were found in levels of negative symptoms and age between the two groups with chronic patients scoring higher on negative symptoms and being older. In the cognitive remediation study a significant improvement was observed in patients in the domain of executive function and a reduction in negative symptoms following completion of the intervention. Conclusion First episode and chronic schizophrenia patients display significant cognitive deficits across all domains when tested using the CANTAB®. Some of these deficits appear to be independent of the length of the illness but dependent on negative symptoms. This study demonstrates that cognitive deficits exist across all patient groups regardless of age, gender, pre-morbid IQ, years in education and ethnicity. Cognitive remediation therapy has also been shown to be effective in improving cognitive functioning in patients.

This thesis deals with possibilities of cognitive development support of adolescents with learning disabilities. The theoretical part first introduces cognitive deficits which are typical for these disabilities. Then it focuses on particular possibilities for adolescents with learning disabilities and how to support their cognitive development. Attention is paid to the use of modern information technologies and applications for children and adolescents with learning disabilities. The thesis also includes a research that attempts to verify the effectiveness of application called Tablexia. Although the results do not confirm the clear efficiency of cognitive training with this application, optional ways to capture the effectiveness better are discussed.

Early-life stress, consisting of several stressors appears to be associated with several impacts on the brain. The impacts of stress seem to be more vulnerable to the developing brain as it undergoes important changes during childhood. This thesis aims to present the association between childhood maltreatment, which is a form of early-life stress, and affected brain regions such as the hippocampus, prefrontal cortex, corpus callosum, and the amygdala. The findings in this thesis demonstrated the left hippocampus to be more vulnerable to the effects of maltreatment, corpus callosum appeared to be gender and maltreatment specific, indicating that the corpus callosum were more vulnerable to neglect in boys whereas in females the structure was more vulnerable to sexual abuse. The prefrontal cortex demonstrated a marked reduction in gray matter, and the amygdala showed increased activation in response to emotional facial expressions. Cognitive deficits as a result of earlylife stress were also discussed, showing that worse intellectual ability and the academic performance had been noted in children with exposure to early-life stress.

The thesis addresses Semantic Verbal Fluency test and its potential as a diagnostics of cognitive deficit at schizophrenic population. Deficit of cognitive functions, presently considered as a core symptom of this disorder, substantially impacts daily life functioning. In particular, discriminant validity of Semantic Verbal Fluency test is examined in a mentally and neurologically healthy population as well as patients diagnosed with schizophrenia aged 18 to 40 years (N=339). Furthermore, results of profound analysis using a qualitative scoring system in a selected sample group (N=47) are presented. Moreover, the study investigates the association of selected demographic variables (gender, age, years of education) with results of Semantic Verbal Fluency test. Results of our statistical analysis reveal that patients diagnosed with schizophrenia performed significantly worse than healthy controls in all examined variables (total word count, total number of semantic clusters, total number of switches, mean cluster size, percent words in clusters, ratio of cluster switches) as compared with mentally and neurologically healthy subjects. Comparable results of the two research groups were attained solely in "number of hard switches" variable. Our results further indicate a significant association between...

La maladie de Parkinson (MP) est une maladie neurodégénérative caractérisée par une perte dopaminergique (DA) de la voie nigro-striée. Cette dégénérescence des neurones DA, induit un déséquilibre entre les transmissions dopaminergique, GABAergique et glutamatergique au sein des ganglions de la base qui se traduit par des troubles de l'excitabilité neuronale aboutissant à l'apparition des symptômes moteurs et non-moteurs. Nous avons étudié l'effet de la modulation des canaux SK et Kv4 par des toxines issues de venins d'animaux. Pour ce faire, nous avons utilisé deux modèles lésionnels à la 6-hydroxydopamine (6-OHDA): une lésion bilatérale partielle du striatum mimant la phase précoce de la MP pour tester les déficits cognitifs et émotionnels, et une lésion unilatérale totale au niveau de la substance noire mimant la rigidité et la bradykinésie en phase tardive pour tester les déficits moteurs. Nos résultats montrent que le blocage des canaux SK par l'apamine (injection systémique, 0.1-0.3 mg/kg) améliore partiellement et transitoirement les déficits moteurs dans le test du cylindre et la rotation induite par l'apomorphine dans le modèle tardif de la MP. L'AmmTX3 (injection intrastriatale, 0.2-0.4 g), réduit les déficits moteurs et restaure des comportements cognitifs déficitaires (mémoire sociale et spatiale à court terme) et émotionnels (anxiété), après une dégénérescence DA bilatérale et partielle. L'ensemble de ces données suggère que l'inhibition pharmacologique de l'activité des canaux SK par l'apamine et Kv4 par l'AmmTX3, pourrait représenter une voie thérapeutique innovatrice quant au traitement des déficits moteurs, cognitifs et émotionnels de la MP. / Parkinson's disease (PD) is a neurodegenerative disease associated to a loss of dopaminergic nigrostriatal pathway that innervates the basal ganglia (GB). The DA neuron degeneration in PD induces imbalance between dopaminergic transmission, GABAergic and glutamatergic resulting in impaired neuronal excitability leading to the onset of motor and non-motor symptoms. Potassium channels, Kv4 and SK, are extensively involved in the phenomenon of neuronal excitability. We addressed the question of whether further blockade of SK or Kv4 activity could restore normal GB function in vivo. In this aim, we used a neurotoxin, 6-hydroxydopamine (6-OHDA) to produce two lesional models of Parkinson's disease in rats that mimics the cognitive and emotional deficits of the early phase of PD (partial and bilateral striatal lesions) and the motor deficits observed in the late phase of the disease (total unilateral nigral lesion). Apamin from bee venom (systemic injection, 0.1-0.3 mg/kg) and AmmTX3 from scorpion venom (intrastriatal injection, 0.2-0.4 g) were chosen to block SK and Kv4 channels respectively.In a first study, apamin treatment partially reduced motor deficits in the cylinder test and the rotation induced by apomorphine. In the second study, the AmmTX3 also decreased parkinsonian motor deficits. This late toxin restored cognitive behaviors (short-term social and spatial memory) and emotion (anxiety).Taken together, these results underlie the importance of SK channels as modulators of neuronal excitability of Kv4 channels as players of the homeostatic responses, and more importantly, provide potential targets for adjunctive therapies for Parkinson's disease.

Made available in DSpace on 2014-12-17T14:46:37Z (GMT). No. of bitstreams: 1 MarceloHAFS.pdf: 506183 bytes, checksum: c43dcd682bf1e3a575d5edfb73bf8807 (MD5) Previous issue date: 2008-10-10 / This study intended to evaluate the maze test accuracy in cognitive deficit screening in elderly with or without neuropsychological pathology. The sample included 40 healthy young (18-25 years old; mean- 21 ? 1.6), 40 healthy old (60-77 years old; mean- 67 ? 5.1) and 18 patients with probable diagnosis of Alzheimer s disease initial stage (52-90 years old; mean- 78 ? 9.2). Data analysis was made using Anova with Tukey s post hoc, multiple linear regression analysis and ROC curve analysis. According to Tukey s test Alzheimer patients spent more time (46843 ? 37926 ms) to execute the test than healthy young (5482 ? 2873 ms; p= 0.0001) and elderly (17978 ? 13700; p= 0.0001); healthy young executed test n lower time (p= 0.035). According to the regression analysis of age, education level and cognitive performance of the three groups, the cognitive performance was the predictor of the execution time. When analyzing young and elderly only age was the predictor and the cognitive performance was the only factor to influence the test of old aged healthy and patients. The ROC curve analysis indicated 72% accuracy for young and elderly and 36% for healthy and elderly patients. The maze execution time represented a better balance between sensibility (75%) and the specificity (61%) was near 13575 ms, indicating that those subjects that execute the maze in a time higher to this value may show cognitive deficit related to the executive function. According to the results it is suggested that the maze test used in this study shows a good accuracy in the cognitive deficit tracking and may discriminate age changes / O objetivo desse estudo foi avaliar a acur?cia do teste de labirinto no rastreamento de d?ficit cognitivo relacionado ? fun??o executiva em idosos com e sem patologia neuropsicol?gica. Participaram da amostra 40 jovens saud?veis com idade entre 18 e 25 anos (21 ? 1,6 anos), 40 idosos saud?veis com idade entre 60 e 77 anos (67 ? 5,1 anos) e 18 pacientes com diagn?stico prov?vel de Doen?a de Alzheimer em est?gio inicial com idade entre 52 e 90 anos (78 ? 9,2 anos). Os dados foram analisados atrav?s da ANOVA, an?lise de regress?o linear m?tipla e an?lise da curva ROC. Atrav?s da ANOVA verificou-se que os pacientes de Alzheimer apresentaram maior tempo de execu??o no teste do que os jovens (pacientes: 46843 ? 37926 ms; jovens: 5482 ? 2873 ms; p= 0,0001) e idosos saud?veis (17978 ? 13700; p= 0,0001) e os idosos apresentaram maior tempo do que os jovens (p= 0,035). Ap?s an?lise de regress?o com as vari?veis idade, escolaridade e desempenho cognitivo considerando os tr?s grupos, observou-se que somente o desempenho cognitivo foi o fator preditor do tempo de execu??o do labirinto. Na an?lise com os jovens e os idosos foi verificado que apenas a idade foi o fator preditivo e na an?lise com os idosos e os pacientes, o desempenho cognitivo foi o ?nico fator influenciador no desempenho do teste. A an?lise da curva ROC com os jovens e idosos foi a que apresentou maior valor da ?rea sob a curva, indicando uma acur?cia 72% e a an?lise dos idosos com os pacientes foi a que apresentou menor ?rea sob a curva, com uma acur?cia de 36%. O tempo de execu??o do labirinto que representou um melhor equil?brio entre a sensibilidade (75%) e a especificidade (61%) foi em torno de 13575 ms, indicando que aqueles indiv?duos que executarem o labirinto no tempo superior a este valor podem apresentar d?ficit cognitivo relacionado ? fun??o executiva. De acordo com os resultados encontrados sugere-se que o teste de labirinto utilizado no estudo apresenta uma boa acur?cia no rastreamento de d?ficit cognitivo podendo discriminar mudan?as decorrentes da idade

La sérotonine est impliquée dans de nombreuses fonctions physiologiques comme la régulation de l’appétit, du sommeil, de la douleur, de l’humeur et de la cognition. Elle agit par l’intermédiaire de différents récepteurs dont la plupart sont couplés aux protéines G. Parmi ceux-ci, les récepteurs 5-HT2A et 5-HT6 suscitent un intérêt particulier car ils sont la cible de nombreux agents thérapeutiques, comme les antidépresseurs et les antipsychotiques de dernière génération. Ces molécules administrées pour traiter la schizophrénie ont des effets bénéfiques sur les symptômes positifs (hallucinations, délires) et négatifs (manque de motivation). Cependant, ils n’ont que peu d’effets sur les déficits cognitifs (troubles de la mémoire de travail, de l’attention, asociabilité) qui compromettent l'intégration sociale et professionnelle des patients ainsi que leur qualité de vie. Ces déficits sont en grande partie retrouvés chez les consommateurs chroniques de cannabis durant l’adolescence suggérant des mécanismes pathologiques communs. La découverte de nouvelles stratégies thérapeutiques pour traiter ces déficits cognitifs constitue donc un enjeu de santé publique majeur.Au cours de mon travail de thèse, j’ai étudié le rôle des récepteurs de la sérotonine, en me focalisant sur les récepteurs 5-HT2A et 5-HT6, dans la modulation de la transmission et la plasticité synaptique au niveau du cortex préfrontal. En combinant des approches biochimiques à des analyses électrophysiologiques et comportementales, j’ai dans un premier temps démontré l'implication des récepteurs 5-HT2A exprimés au niveau des synapses thalamocorticales dans l’induction de la plasticité synaptique et dans la mémoire associative. Dans un deuxième temps, j’ai déterminé les bénéfices du blocage précoce des récepteurs 5-HT6 sur les déficits cognitifs induits dans un modèle neurodéveloppemental de schizophrénie et un modèle de consommation chronique de cannabis durant l’adolescence. Cette étude permet ainsi d’envisager de nouvelles stratégies thérapeutiques pour prévenir l’apparition des déficits cognitifs observés dans les maladies psychiatriques, notamment chez les sujets à risque. / Serotonin is involved in many physiological functions, such as the control of appetite, sleep, pain, mood and cognition. This major neuromodulator acts via different receptors, which are, for the most part, coupled to G-proteins. Among these, 5-HT2A and 5-HT6 receptors are of particular interest since they are the target of many therapeutic drugs, such as antidepressants and last-generation antipsychotics. These are administered to treat schizophrenia and have beneficial effects on positive (hallucinations, delusions) and negative (lack of motivation) symptoms. Nevertheless, they poorly control cognitive deficits (impaired working memory, decreased attention, alteration in social cognition) which severely compromise the social integration of patients and their quality of life. These deficits are also found in chronic cannabis users during adolescence, suggesting common pathological mechanisms. Therefore, the discovery of new therapeutic strategies to treat these cognitive deficits is a major public health issue.During my thesis work, I studied the role of serotonin receptors, focusing on 5-HT2A and 5-HT6 receptors, in the modulation of synaptic transmission and plasticity in the prefrontal cortex. By combining biochemical approaches with electrophysiological and behavioral analyses, I initially demonstrated that 5-HT2A receptors expressed at thalamocortical synapses play a crucial role in the induction of synaptic plasticity and in associative memory. Secondly, I demonstrated the benefits of early blockade of 5-HT6 receptors for preventing cognitive deficits induced in a neurodevelopmental model of schizophrenia and a model of chronic cannabis abuse during adolescence. These studies offer new therapeutic strategies to prevent the emergence of cognitive deficits and conversion to schizophrenia in at-risk subjects.

This diploma thesis is introducing Trail Making Test - Part A as a tool for assessment of cognitive deficit in schizophrenia. Cognitive deficit is one of the core symptoms of schizophrenia which plays a key role in the final psychosocial functioning in the life of people with schizophrenia. Therefore, it is important to pay attention to the efficiency of interventions focused on improving cognitive functions and the quality of diagnostics. In this paper we were verifying a validity of TMT-A in use of cognitive deficit in schizophrenia. We have found out that the test discriminates between clinical and healthy population (n=332) quite well. Participants with schizophrenia scored significantly worse than the healthy volunteers in the time variable. We have not found any difference in the number of errors in TMT-A between the groups. In the ROC analysis we were verifying if the TMT-A has enough good sensitivity and specificity and we found positive results. The AUC value was large for the age category of 18-44 as well as for particular age subgroups. Using the regression analysis we controlled for the demographic differences of the clinical and healthy groups and we estimated the difference between the performance of clinical and healthy population of about 11,9 seconds. Due to the general nature of...

No description available.

Mild cognitive deficits that negatively impact self-management education-related outcomes may be present in a proportion of cardiac rehabilitation patients and the degree of impairment may vary by the type of coronary revascularization procedure. The purpose of this study was to compare cognitive function, as measured by the Montreal Cognitive Assessment (MoCA), between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) patients, and to determine independent variables of MoCA score. In a cross-sectional study, 78 cardiac rehabilitation patients (CABG n = 38, PCI n = 40) completed the MoCA. Demographics were collected and disease burden was calculated using the age-adjusted Charlson Comorbidity Index (ACCI). Mild cognitive deficits (MoCA ≤26) were present in 55.3% CABG and 30.0% PCI patients. An independent Student’s t test showed that MoCA scores were significantly lower among CABG patients (mean = 24.5, SD = 3.3) compared to PCI patients (M = 26.7, SD = 2.7), t (76) = 3.15, p < 0.01. Descriptive analyses of cognitive domain scores indicated that deficits in short-term memory and language were present among CABG patients. Using a backward regression, coronary revascularization procedure (CABG vs. PCI) (p = 0.006) and disease burden (ACCI) (p = 0.015) remained significant, while heart failure diagnosis became non-significant and was removed from the model (F (2, 75) = 8.382, p < 0.001). The final model explained 16.1% of the total variance in MoCA score (adjusted R2 = 0.161). Results indicate that cognitive deficits were present in cardiac rehabilitation participants and associated with the type of coronary revascularization procedure, suggesting the need for formal cognitive screening and adaptation of education interventions in cardiac rehabilitation. A future prospective cohort study is required to establish temporality, and to measure education-related outcomes, such as health-related quality of life (HRQOL) and self-management. / Thesis / Master of Science (MSc) / Cardiac rehabilitation (CR) is a multifaceted program consisting of exercise and education that is essential to the care of post-coronary revascularization patients. While exercise has shown to improve health outcomes, education has demonstrated inconsistent effects. Since education has imposed cognitive demands, this discrepancy in outcomes may, in part, be due to cognitive deficits present in a proportion of program attendees: the degree of impairment may vary by type of coronary revascularization procedure prior to CR. This study compared cognitive function between two groups of coronary revascularization patients, post-coronary bypass surgery and post-coronary angioplasty, and determined independent variables for cognitive function. Results showed that coronary bypass surgery patients had significantly lower cognitive function than coronary angioplasty patients at program intake. Coronary bypass surgery and accumulated disease burden were weakly associated with decreased cognitive function. Cognitive screening and adapted education for patients with cognitive deficits should be considered to improve CR outcomes.