Les études épidémiologiques ont associé la rigidité artérielle au déclin cognitif et à la démence. Cependant ses effets sur la biologie du cerveau restent méconnus. Dans notre première étude, en utilisant un nouveau modèle murin de rigidité artérielle, nous avons voulu caractériser les effets de la rigidité artérielle sur le cerveau indépendamment de l’âge et de l’augmentation de la pression artérielle. Les résultats indiquent que la rigidité artérielle altère la régulation du flux sanguin cérébral et l'intégrité du système vasculaire cérébral, endommageant la barrière hémato-encéphalique et conduisant à des déficits cognitifs. Le débit sanguin cérébral est altéré au repos ainsi qu’au niveau de ses mécanismes de régulation comme l’autorégulation cérébrale, le couplage neurovasculaire et la fonction endothéliale. Dans notre deuxième étude nous avons cherché à comprendre le dimorphisme sexuel pour la rigidité artérielle et ses conséquences sur le cerveau dans le même modèle. Nos résultats montrent que la rigidité artérielle entraîne une altération du couplage neurovasculaire et de la réactivité vasculaire dépendante de l’endothélium chez les souris mâles mais pas chez les souris femelles reproductives. Chez les souris ovariectomisées, cette protection a été supprimée, mais a été restaurée par un traitement à l’œstradiol. Dans la troisième étude, nous avons voulu étudier la possibilité de prévenir la rigidité artérielle et ses effets subséquents sur le cerveau. Pour cette étude, nous avons utilisé la vitamine K (VK) (phylloquinone ou VK1 et la ménaquinone-4 ou MK-4) vu son action anti-calcifiante et ses effets bénéfiques sur les fonctions cognitives observés dans d’autres modèles animaux et chez l’homme. Cette étude a démontré que la VK améliore les fonctions cognitives et rétablit le débit sanguin cérébral au repos et diminue la calcification vasculaire. Les capacités d’apprentissage s’amplifient avec l’apport de la VK alimentaire et la concentration de la VK au cerveau. Ces études permettent une meilleure compréhension de la rigidité artérielle et démontrent le potentiel de la VK et le traitement hormonal par l’œstradiol dans la prévention de ses effets sur le cerveau. Cependant, d’autres études sont nécessaires pour déterminer tous les mécanismes impliqués dans la protection du cerveau par la VK et l’œstradiol. / Epidemiological studies have associated arterial stiffness with cognitive decline and dementia. However, its effects on the brain biology remain unknown. In our first study, using a new murine model of arterial stiffness, we wanted to characterize the effects of arterial stiffness on the brain independently of age and pressure. Our results indicate that arterial stiffness impairs the regulation of cerebral blood flow and the integrity of the cerebrovascular system, damaging the blood-brain barrier and leading to cognitive deficits. Arterial stiffness results in significant alterations in resting cerebral blood flow and mechanisms regulating cerebral blood flow such as cerebral autoregulation, neurovascular coupling, and endothelial function. In our second study we sought to understand sexual dimorphism in arterial stiffness and its consequences on the brain in the same model. Our results show that arterial stiffness leads to impaired neurovascular coupling and endothelial-dependent vascular reactivity in male mice but not in female reproductive mice. In ovariectomized mice this protection was suppressed but was restored by estradiol treatment. In the third study, we wanted to study the possibility of preventing arterial stiffness and its subsequent effects on the brain. In this study, we used vitamin K (phylloquinone or VK1 and menaquinone-4 or MK-4) for its anti-calcifying action and its beneficial effects on the cognitive functions observed in other animal models and in humans. This study demonstrated that VK prevent cognitive impairment in part by restoring the resting cerebral blood flow but also by preventing vascular calcification. Learning abilities increase with the contribution of food VK, which in turn correlates with the VK content of the brain. These studies provide a better understanding of arterial stiffness and demonstrate the potential of VK and hormone therapy with estradiol in preventing its effects on the brain. However, further studies are needed to determine all the mechanisms involved in the brain protection by VK and estradiol.

This diploma thesis deals with the topic of cognitive development and possibilities of cognitive screening in preschool age. The aim of this study is to present a new battery of interactive games developed as a screening tool under the patronage of National Institute of Mental Health (NUDZ) within the project TA ČR TL02000561. The theoretical part is concentrating on cognitive development of preschool children with focus on selected cognitive functions and methods of testing. The empirical part is presenting results of the pilot testing of this battery with preschool and younger school aged children. The primary aim was to verify functionality and comprehensibility of each game in the battery. Finding of this study will be used to optimize this battery.

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.

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Obesity is associated with deficits in cognitive function, particularly within the domain of executive function (EF). EF refers to higher order cognitive processes that regulate our ability to sustain attention, inhibit subconscious tendencies, remember and manipulate information for immediate use, and remain cognitively flexible. Deficits in EF in overweight and obese individuals may impact the success of weight loss and maintenance efforts. Therefore, understanding the biological links between obesity and EF, as well as the ability to reverse EF deficits with weight loss, is imperative. The first study aimed to determine the effect of weight loss in overweight and obese, middle-aged and older adults on serum brain-derived neurotrophic fact (BDNF), S100 calcium binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Serum samples (n=21; 50-75 years, BMI 25-40 kg/m2) were pooled from two prior weight loss studies. Fasting blood measurements were taken before and after 8- or 12-weeks of hypocaloric diet-induced weight loss (1200 or 1500 kcal/d). Body Mass Index (BMI), body weight, waist circumference, and percent body fat (All p<0.001) decreased with weight loss. Serum BDNF (p=0.871), S100B (p=0.898), and GFAP (p=0.506) did not change following weight loss. The second study aimed to determine the correlation between the magnitude of change in serum BDNF, S100B, and GFAP and the magnitude of improvement in EF performance on three computer-based tests. Participants (n=8; 50-75 years, BMI 25-40 kg/m2) completed 4-weeks of hypocaloric diet-induced weight loss (1200 or 1500 kcal/d), followed by 4-weeks of weight maintenance (hypocaloric diet + steps/d goal). Fasting blood and EF measurements were completed at baseline, and weeks 4 and 8. BMI (p=0.001), body weight (p=0.001), waist circumference (p=0.002), and percent body fat (p=0.001) decreased from baseline to week 8. Serum BDNF (p=0.359), S100B (p=0.277), and GFAP (p=0.585) did not change following weight loss. Go/No-Go (GNG) errors of commission (p=0.009) and AX-Continuous Performance Test (AX-CPT) correct response time (p=0.041) decreased following the weight loss. The change in serum GFAP was inversely correlated with GNG errors of omission (r=-0.716, p=0.046) and AX-CPT correct hits (r=-0.737, p=0.037), and positively correlated with AX-CPT correct response time (r=0.859, p=0.006). In conclusion, although weight loss does not influence serum BDNF, S100B, or GFAP levels, it may have a positive effect on inhibitory control in overweight and obese, middle-aged and older adults. Further research is needed to understand the relationship between serum BDNF, S100B, and GFAP and executive function. / Master of Science / Obesity is associated with lower brain function, particularly in executive function (EF). EF refers to advanced thought processes that help to maintain focus, practice self-control, solve problems, and easily switch between tasks. Lower EF in individuals with overweight and obesity may impact the success of weight loss and maintenance efforts. Because of this, understanding body processes that may link obesity and lower EF, as well as the ability to improve EF with weight loss, is very important. The first study aimed to determine the effect of weight loss on blood proteins responsible for brain health: brain-derived neurotrophic fact (BDNF), S100 calcium binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Twenty-one blood samples from overweight and obese, middle-aged and older adults were combined from two completed weight loss studies. In these studies, blood was measured before and after 8- or 12-weeks of a weight loss (low calorie diet;1200 or 1500 Calories per day). Body Mass Index (BMI), body weight, waist circumference, and percent body fat all decreased with weight loss; however, levels of BDNF, S100B, and GFAP in the blood did not change. The second study aimed to determine the relationship between blood BDNF, S100B, and GFAP and performance on three computer-based tests of EF before and after weight loss. Eight overweight and obese, middle-aged and older adults completed 4-weeks of weight loss (low-calorie diet; 1200 or 1500 Calories per day), followed by 4-weeks of weight maintenance. BMI, body weight, waist circumference, and percent body fat all decreased following the weight loss and maintenance intervention (week 8). Blood BDNF, S100B, and GFAP levels did not change, but performance on two EF measures improved: participants made less errors of commission (doing something when not supposed to) and had faster reaction time following the intervention, indicating better self-control. Additionally, greater increases in GFAP were associated with less errors of omission (not doing something when supposed to), fewer correct responses, and slower reaction time. In conclusion, although weight loss did not affect blood BDNF, S100B, or GFAP levels, it may improve self-control in overweight and obese, middle-aged and older adults. Further research is needed to understand the relationship between weight loss, blood proteins of brain health, and EF.

Traumatic brain injury (TBI) has a dramatic impact on our society in terms of mortality, morbidity, and inherently high financial costs. Formidable research efforts are being addressed to the identification of neuroprotective agents capable of ameliorating the neurological outcome after TBI. Preclinical studies have recently demonstrated lithium to be a promising neuroprotective agent for both acute ischemic brain injury and chronic neurodegenerative disease. In light of these encouraging data, we designed a lateral fluid-percussion injury (FPI) study aimed at investigating the role of early post-traumatic administration of lithium as a strategy for reducing TBI-induced motor and cognitive deficits. The optimal dose of this agent and the time window for its administration have been determined on the basis of data derived from the assessment of motor and cognitive functioning in experimental animals, as well as from the stereological quantification of neuronal survival (PID 7) within the CA3 and hilar regions of the hippocampus ipsilateral to the FPI. In addition, we attempted to elucidate the mechanisms underlying the neuroprotective properties of this drug via western blot analysis of levels of the pro-apoptotic marker caspase-3 (PID 1, 7) and two neuroplasticity markers, growth associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) (PID 1, 7, 21). Our findings indicate that low-dose lithium chloride (0.125 or 0.25 mmol/kg), given either 30 min or 8 hr after lateral FPI significantly ameliorates injury-induced cognitive and motor impairment. Specifically, cell survival in the CA3 region of the hippocampus of the injured lithium-treated animals (but not in the hilus) was significantly increased compared to injured vehicle-treated animals. Western blot analyses revealed a significant increase in GAP-43 levels on PID 7 in injured animals when treated with lithium, indicating a possible mechanism for lithium-induced neuroprotection. In contrast, BDNF levels were relatively unchanged until PID 21, and caspase-3 activation was not observed at all, suggesting that these proteins play less significant roles in the observed neuroprotective effects of lithium treatment after lateral FPI. Early administration of lithium, within 8 hours after TBI, holds promise as an effective therapy to ameliorate postinjury neurobehavioral deficits and warrants further investigation in clinical TBI studies.

OF THE THESIS The topic of this thesis is to study the cognitive processes (especially perception, imagination and thinking) of blind pupils through experiments with geometric objects. Tools of the experiment are four tasks (two for one pupil, two for a pair of pupils) that are recorded, transcribed into written protocols and analysed. An overview of the involved cognitive functions or naming of missing cognitive functions has been complied on basis of the specialised literature as a theoretical solution of analysis. Findings of psychology of mathematics didactic were other important theoretical starting points. The ones which are devoted to the tactile perception (of geometrical objects), stages of Piaget operation developments, cognitive mechanisms in mathematics and importance of communication in mathematics or geometry teaching are involved in the theses. Analysis of the experiments involves observations of the tactile perception, imaginations, thinking, cognitive processes, speech and communication, and other occurrences essential for specific tasks.

The thesis Dynamic Loewenstein occupational therapy cognitive assessment in individuals after obtaining brain injury in working age deals with a comparison of the level of the brain injured and non-brain injured people's cognitive functions with the aid of the Loewenstein Occupational Therapy Cognitive Assessment battery (DLOTCA). The theoretical part is focused on an issue of the acquired brain injury, a description of cognitive areas and as well their pathology due to this injury. The aim of the practical part is to test the cognitive functions with the aid of the Loewenstein Occupational Therapy Cognitive Assessment. The survey's main object is the applicability of the working version of the Loewenstein Occupational Therapy Cognitive Assessment battery (DLOTCA), its translated version. The testing was carried out on seventy probands devided into three groups. Healthy people (n=50), cerebrovascular accident patients (n=10) and traumatic brain injury patients (n=10). Key words: obtained brain injury Dynamic Loewenstein occupational therapy cognitive assessment cognitive function working age occupational therapy cognitive assessment

The thesis Dynamic Loewenstein occupational therapy cognitive assessment in individuals after obtaining brain injury in working age deals with a comparison of the level of the brain injured and non-brain injured people's cognitive functions with the aid of the Loewenstein Occupational Therapy Cognitive Assessment battery (DLOTCA). The theoretical part is focused on an issue of the acquired brain injury, a description of cognitive areas and as well their pathology due to this injury. The aim of the practical part is to test the cognitive functions with the aid of the Loewenstein Occupational Therapy Cognitive Assessment. The survey's main object is the applicability of the working version of the Loewenstein Occupational Therapy Cognitive Assessment battery (DLOTCA), its translated version. The testing was carried out on seventy probands devided into three groups. Healthy people (n=50), cerebrovascular accident patients (n=10) and traumatic brain injury patients (n=10). Test results confirm all the stated hypothesis because it did not meet the prerequisites of the total evaluation. We assumed that a person healthy population will reach 100% success rate testing, which some individuals reached. In the assessment of persons with stroke by 6 out of 10 tested achieved a lower evaluation scores in most...

研究目的：本研究的目的，是以縱貫研究的方式探討自閉症類疾患兒童自學齡前期至學齡期的臨床診斷穩定度、自閉症狀嚴重度變化、適應行為型態與其變化、內外化行為。 研究方法：本研究納入28名自閉症類疾患與18位非自閉症類疾患，於三個時間點進行評估：時間點一平均生理年齡為2歲半、時間點二為4歲、時間點三為9歲半。本研究分析三個時間點之臨床診斷穩定度以及後兩個時間點之評估資料。症狀嚴重度方面，以自閉症診斷會談問卷修訂版之晤談評估；適應行為方面，以文蘭適應行為量表第二版評估；認知功能方面，時間點二時以穆林發展量表評估，時間點三時使用魏氏兒童智力量表第四版評估；內外化行為方面，時間點三時以阿肯巴克實證衡鑑系統中的兒童行為檢核表評估。 研究結果：本研究結果顯示，自閉症類疾患從學齡前期至學齡期的臨床診斷穩定度高，若分亞型來看，自閉性疾患的診斷穩定度比其他未註明之廣泛性發展疾患高。症狀嚴重度方面，學齡期時自閉症類疾患兒童的溝通、侷限及重複刻板行為有顯著改善，社交行為亦有改善趨勢。適應行為方面，學齡前期及學齡期皆未發現自閉症類疾患與非自閉症類疾患之表現型態有差異，兩組在社會化領域的表現皆較其他領域來得差。自閉症類疾患的適應行為於學齡期時，年齡當量顯著增加，但社會化適應行為標準分數反而退步；進一步以認知功能分組檢視，則發現高功能自閉症類疾患在日常生活技巧與社會化領域的進步幅度顯著較多。內外化行為方面，學齡期時自閉症類疾患個案的退縮/憂鬱分量尺與社會問題分量尺之分數高於非自閉症類疾患，且自閉症類疾患在退縮/憂鬱、社會問題、注意力問題等三個分量尺上，皆有超過一半的個案達到邊緣範圍以上之分數；未發現內外化行為與自閉症狀嚴重度之間的相關。 結論：自閉症類疾患兒童到了學齡期大部分仍維持臨床診斷，顯示其自閉特徵仍然穩定存在，不過症狀嚴重度的整體趨勢會隨著年紀改善；但若以個體差異來看，每位個案進步的程度呈現高異質性，每位個案症狀改變的程度可能不同。自閉症類兒童的社會化適應行為從學齡前期至學齡期皆為其弱項，雖適應行為會隨著年齡進步，但社會化適應行為仍追不上同儕程度；高功能自閉症類疾患兒童的適應行為在日常生活技巧與社會化領域的進步幅度顯著較多，可能與認知功能有關。內外化行為方面，自閉症類疾患兒童的退縮/憂鬱問題、社會問題、注意力問題較多，但與症狀嚴重度無關。 / Purposes: The purpose of this longitudinal study was to examine the stability of clinical diagnosis, symptom severity, adaptive function and enternal/external behavior from toddler to school age in children with autism spectrum disorders (ASDs). Methods: Twenty eight children diagnosed with ASDs and eighteen children with Non-ASDs participated at time 1 (mean chronological age was 2.5 years old), and then followed at time 2 (mean chronological age was 4 years old) and at time 3 (mean chronological age was 9.5 years old). This study examines the stability of clinical diagnosis from time 1 to time 3, and analyze the measurement data between time 2 and time 3. Autism Diagnostic Interview-Revised (ADI-R) was used to measure autistic symptom severity at time 2 and time 3; Vineland Adaptive Behavior Scales-II (VABS-II) was used to measure daily adaptive behavior at time 2 and time 3; Mullen Scale of Early Learning (MSEL) or Wechsler intelligence scale for children-Fourth Edition (WISC-IV) was used to measure cognitive function at two time points; Child Behavior Checklist for Ages 6-18 (CBCL/6-18) was used to measure enternal and external behavior at time 3. Results: The stability of clinical diagnosis was high from toddler age to school age, and the stability of Autistic Disorder was higher than Pervasive Developmental Disorder Not Otherwise Specified. The ADI-R scores of communication domain, repetitive and stereotyped behavior domain were decreased at school age, while reciprocal social interaction domain was also declined but no significant difference. All domains of VABS-II standard score were no significant difference between ASDs and Non-ASDs at two time point, and the score of social domain was worst in both two groups. The VABS-II standard score of social domain was reduced although the age equivalent was increased at school age, and the standard score of other domains were no significant difference between the two time points but all age equivalents were improved at school age. Dividing ASDs to high-function ASDs and low-function ASDs to analyze the growth rate of adaption behaviors, the results indicated that the growth rate of adaption behaviors were higher in high-function ASDs at daily skill domain and social domain. Children with ASDs had significant higher scores on Withdrawn/Depressed scale and Social Problem scale than Non-ASDs in CBCL, and over 50 percent of ASDs scored above the borderline range at Withdrawn/Depressed scale, Social Problem scale and Attention Problem scale. In addition, there were no significant correlations between CBCL and ADI-R. Conclusions: In summary, the study showed that most of ASDs sustained the clinical diagnosis from preschool age to school age, however, the autistic symptom severity was declined. Additionally, the improvement of symptom severity of individual ASDs was high variability. The social adaptive behavior was worst in both toddler age and school age in ASDs. Although these children with ASD developed some of adaptive behaviors in the school age, the magnitude of improvement couldn’t equal to the change of their chronological age, especially in socialization domain. The growth rate of daily skill domain and social domain were higher in high-function ASDs than low-function ASDs, might associated with cognitive function. More Children with ASDs had withdrawn/depressed problem, social problem and attention problem, but there were not related to autistic symptom severity.