La maladie d’Alzheimer (MA) et la maladie de Parkinson (MP), sont considérées aujourd’hui comme un problème majeur de santé publique du fait qu’elles sont diagnostiquées trop tardivement et demeurent sans traitement curatif. D’importants efforts doivent donc être mis en œuvre pour identifier des marqueurs précliniques sensibles et spécifiques au risque de développer une maladie neurodégénérative. Dans cette optique, plusieurs auteurs ont récemment montré que les fonctions exécutives et le control locomoteur dans une situation de double tâche, sont altérés aux stades précliniques de la MA et la MP. En routine clinique les médecins sont des fois confrontées à ces individus ayant des troubles exécutivo-locomoteurs mais qui ne sont pas immédiatement repérés en raison de leurs capacités de réserves particulièrement élevées. Pris ensemble, les travaux de cette thèse s’articulent autour d’un large spectre des notions liées au vieillissement normal et pathologique qui sont les fonctions exécutives, le contrôle locomoteur et la réserve cognitive. L’originalité de cette thèse réside dans le développement d’un « nouveau test neuropsychologique : Le Stroop Switching Card Test » évaluant l’efficience exécutive globale avec des mesures spécifiques à chaque composante et deux nouvelles mesures de la réserve cognitive dont une qualitative (i.e., un nouveau questionnaire) et l’autre quantitative (seuil du déclin exécutif associé à une basse réserve cognitive). En parallèle nous avons développé trois nouveaux paradigmes de doubles tâches fondés sur le profil physiopathologique de la MA et la MP. Les résultats révèlent que la batterie de tests que nous proposons présente un intérêt potentiel pour détecter précocement un déclin exécutif chez les sujets âgés, mais aussi pour distinguer le vieillissement normal du vieillissement accéléré. En conclusion, les résultats préliminaires de cette thèse confirment la validité de nouveaux tests dans l’évaluation des fonctions exécutive, de la réserve cognitive et du contrôle locomoteur. Des études longitudinales sont nécessaires pour confirmer que ces outils pourraient avoir une valeur ajoutée dans le diagnostic précoce et différencié des MA et MP. / To date, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are diagnosed in the advanced stage of degenerative brain processes, when clinical symptoms occur. In the absence of curative therapy, current research is focused on prevention by identifying subtle signs of early stage neurodegeneration. In the light of these clinical perspectives, recent research in behavioral neurosciences has already found that executive functions (i.e., notably inhibition and switching) and gait control as assessed by standard neuropsychological tests (e.g., Stroop Test and Trail Making Test) and dual-task walking paradigms, respectively, are already altered at both the preclinical and prodromal phases of AD and PD. We would argue that it is imperative to take into account factors modulating the capacity to cope with age-related brain changes, among which the most important is the cognitive reserve. Together, the main goals of this thesis are to develop: (i) a new neuropsychological test, assessing executive functions, separately and together, (ii) new measures of CR; and (iii) new dual-task walking paradigms based on the neuropathological profiles of AD and PD, by manipulating both the nature of executive processes and cognitive load. These tools were validated in healthy young adults and older adults with a high sensitivity. Specifically, we have found that these tools allow detecting early executive decline. Furthermore, they allow to differentiate normal aging from accelerated aging. In conclusion, the preliminary results of this thesis confirm the validity of the new tests in the evaluation of executive function, cognitive reserve and gait control. Longitudinal studies are needed to confirm that these tools could have an added value in the early and differential diagnosis of AD and PD.

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This Master thesis is focused on ecological validity of a cognitive training in university students. Forty-five students participated in three months research during which 30 of them took regular personalized cognitive training using CogniFit programme on their computers. The study examines the impact of the cogntitive training on everyday cognitive functioning of students. The scientific methods used for the ecological validity research were the following self-reporting questionnaires: Cognititive Failure Questionnaire, Everyday Memory Questionnaire and Dysexecutive Questinnaire. Students also filled in Schwartz Outcome Scale - 10 and Self-image questionnaire for detailed exploration of more variables. For the research, we applied test-retest design and used control group of fifteen students for results comparison. Analysis of the gathered data proved little evidence of ecological validity of cognitive training, which can be attributed to considerable cognitive stress at students. An unexpected outcome of the study which proved to be very significant is relation between executive functions and well-being of a student. This relation was confirmed repeatedly. Possible improvements of methodology and also problem with randomization of students is discussed. Proposal for the further development of...

Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2018-09-21T12:01:19Z No. of bitstreams: 1 DAIANE_BORBA_DE_LIMA_TES.pdf: 957011 bytes, checksum: aabf702a83978ff60b063787acb5fb76 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-09-24T11:27:34Z (GMT) No. of bitstreams: 1 DAIANE_BORBA_DE_LIMA_TES.pdf: 957011 bytes, checksum: aabf702a83978ff60b063787acb5fb76 (MD5) / Made available in DSpace on 2018-09-24T11:40:07Z (GMT). No. of bitstreams: 1 DAIANE_BORBA_DE_LIMA_TES.pdf: 957011 bytes, checksum: aabf702a83978ff60b063787acb5fb76 (MD5) Previous issue date: 2017-08-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / It is widely accepted that normal aging is accompanied by changes in cognitive abilities. It is also important to note that the pattern and degree of cognitive alterations in non-demented older adults is heterogeneous, with some of them showing significant impairments while others maintain relatively constant performances throughout aging. Among the factors that seem capable to modulate cognitive integrity on older age is life style. There are a number of suggestions that social, intellectual and physical activities enhance cognitive reserve and protect against cognitive decline. The mechanisms related to these benefits are still unknown, but intervention studies with older adults suggest that BDNF could be a mediator of the benefits on cognitive function induced by physical activity. However, studies on the effects of social and intellectual activities on this neurotrophin are scarce. In the present study, it were evaluated the lifestyle effects (social, intellectual and physical activities) on cognitive aspects and BDNF levels of healthy older adults. The relation between social, intellectual and physical activities, BDNF levels and neuropsychology performance (attention, working memory and executive function tests) was analyzed in a sample of healthy older adults (? 60 years old, n=58). The results showed no significant associations between social or intellectual activity levels with BDNF levels, but the group with the lowest level of physical activity had the lowest BDNF levels. Additionally, the findings did not identify consistent effects of these lifestyle components on cognitive functions. Since it is possible that the neuropsychological tests used had not enough sensibility to identify lifestyle effects on cognition, it was investigated a more sensible task: an incidental contextual memory test. Thus, it was evaluated the effect of physical activity on contextual memory of older adults (? 60 years old, n=52). It was observed that higher physical activity levels improved free recall and recognition of contextual memory. In addition, the combination of higher physical activity levels and an associative encoding instruction resulted in the better contextual memory in free recall. The results described above indicate that physical activity modulates BDNF levels and has the potential to improve cognitive reserve and cognitive performance. Additionally, the effects of intellectual and social activities are probably not sufficiently robust to be identified in transversal experimental designs of healthy older adults, especially when the subjects operate in a relatively narrow range of these lifestyle aspects. / O envelhecimento normal ? acompanhado por mudan?as em habilidades cognitivas. ? importante notar que o padr?o e o grau de altera??es cognitivas em idosos n?o demenciados s?o heterog?neos, enquanto alguns apresentam preju?zos significativos, outros mant?m a performance constante ao longo do envelhecimento. Entre os fatores que parecem ser capazes de modular a integridade cognitiva no envelhecimento est? o estilo de vida. H? v?rias sugest?es de que as atividades sociais, intelectuais e f?sicas melhoram a reserva cognitiva e protegem contra o decl?nio cognitivo. Os mecanismos relacionados a esses benef?cios ainda s?o desconhecidos, mas estudos de interven??o com idosos sugerem que o BDNF (fator neurotr?fico derivado do c?rebro) pode ser um mediador dos benef?cios na fun??o cognitiva induzidos pela atividade f?sica. Entretanto, estudos a respeito dos efeitos das atividades sociais e intelectuais sobre esta neurotrofina s?o escassos. No presente estudo, foram avaliados os efeitos do estilo de vida (atividades sociais, intelectuais e f?sicas) sobre aspectos cognitivos e n?veis de BDNF em idosos saud?veis. A rela??o entre as atividades sociais, intelectuais e f?sicas, os n?veis de BDNF e a performance neuropsicol?gica (aten??o, mem?ria operacional e fun??o executiva) foi analisada em uma amostra de idosos saud?veis (? 60 anos de idade, n=58). Os resultados n?o mostraram associa??es significativas entre as atividades sociais e intelectuais e os n?veis de BDNF, entretanto, o grupo com n?vel mais baixo de atividade f?sica teve n?veis mais baixos de BDNF. Adicionalmente, os achados n?o identificaram efeitos consistentes destes componentes do estilo de vida sobre as fun??es cognitivas. A possibilidade deste resultado negativo ser uma consequ?ncia da falta de sensibilidade dos testes neuropsicol?gicos utilizados levou ? investiga??o de uma tarefa mais sens?vel: a de mem?ria contextual incidental. Desta forma, foi avaliado o efeito da atividade f?sica sobre a mem?ria contextual de idosos (? 60 anos de idade, n=52). Observou-se que n?veis mais altos de atividade f?sica melhoraram a evoca??o livre e reconhecimento de mem?ria contextual. Al?m disso, uma instru??o codificadora associativa combinada a n?veis maiores de atividade f?sica gerou uma melhora mais pronunciada na mem?ria contextual, principalmente na evoca??o livre. Os resultados apresentados nesta tese indicam que atividade f?sica modula os n?veis de BDNF e tem potencial para beneficiar a reserva cognitiva e a performance cognitiva. Adicionalmente, os efeitos das atividades intelectuais e sociais provavelmente n?o s?o suficientemente robustos para serem identificados em desenhos experimentais transversais especialmente quando os sujeitos se encontram em um intervalo relativamente estreito destes aspectos do estilo de vida.

Mindfulness-based meditation practices involve various attentional skills including the ability to sustain and focus ones attention. During a simple mindfulness based breath awareness meditation, sustained attention is required to maintain focus on the breath while meta-cognitive awareness and executive control are required to detect and correct mind wandering. The purpose of this thesis was to investigate whether a simple, mindfulness based breath awareness meditation, administered over a short period to meditation naïve individuals could modulate core attentional functions and associated task related neural activity. Two longitudinal randomised control studies were conducted. The aim of the first study was to establish if said modulations were possible in a sample of healthy adults, meeting a current research need for longitudinal evidence in this field and providing important information regarding a potential mechanism for the salutary effects widely observed from the use of mindfulness based interventions. It was found that short term engagement with a mindfulness based breath awareness meditation can modulate core attentional functions and task related neural activity, with specific modulations found in electrophysiological markers of sustained attention to the goal/task at hand and perceptual stimulus discrimination. In line with current theoretical models it is argued that modulations to such core attentional processes following short term training may provide a platform upon which mindfulness related salutary effects are built. The second study was designed to establish if such modulations were possible in older adults. It is argued that mindfulness training may have utility for increasing cognitive reserve, a potential mechanism by which age related declines in cognitive functions may be mitigated. It was found that both behavioural and electrophysiological markers of core attentional functions were modulated following 8 weeks mindfulness training but not following a matched active control group condition (simple brain training exercises). The reviewed extant evidence and findings of this study suggest that mindfulness meditation may enhance cognitive reserve through the repeated activation of attentional functions and associated neural activity during practice and are consistent with recent theoretical models of cognitive reserve. The potential for mindfulness training to positively modulate core attentional functions in older adults and to potentially impact cognitive ageing demands further investigation.

Cognitive impairment is common in multiple sclerosis (MS), with as many as 70% of patients with MS affected. Individuals with MS who experience cognitive deficits are less likely to be employed, and may have more difficulty performing independent activities of daily living. Most commonly, deficits are observed in processing speed, complex attention, and memory. Because lesion location varies widely among individuals, no clear pattern of cognitive dysfunction in MS has emerged. However, a number of risk and protective factors may influence the likelihood of individuals to develop and/or express dysfunction, though the contribution of each to specific domains of cognition has not been fully explored. Recently, support for the cognitive reserve hypothesis (i.e., enriching life experiences protect against cognitive decline despite disease burden) has emerged in the MS literature. The current study investigated the contributions of cognitive reserve to learning and memory functioning in MS and the interaction of cognitive reserve variables and risk factors known to impact cognitive functioning in individuals with MS. Finding revealed cognitive reserve protects against decline in the domains of processing speed and complex attention. Furthermore, indirect protective effects of cognitive reserve through these domains were observed for verbal learning and memory. Finally, in line with previous literature, cognitive dysfunction predicted employment status of the current sample. Clinical implications and future directions for intervention efforts are discussed.

Lors du vieillissement sain, et malgré une augmentation de la fréquence d’apparition du manque du mot, les personnes âgées manifestent une préservation des performances de dénomination orale d’objets (DO), suggérant la mise en place de stratégies efficaces de récupération et de sélection de l’information lexicale. Dans ce travail de thèse, nous avons utilisé une approche méthodologique multimodale afin d’évaluer la nature de ces stratégies. Nous nous sommes plus spécifiquement intéressés aux mécanismes de réorganisation cérébrale ainsi qu’aux activités sociales comme facteur de réserve cognitive. Ce travail de thèse se décompose en cinq études et aborde une perspective homogène (effet de l’âge) et hétérogène (effet des performances) du vieillissement. Nos résultats mettent en évidence l’existence de différents mécanismes de compensation associés au vieillissement sain. Tout d’abord, nous observons que les personnes âgées sont plus lentes que les jeunes adultes lors de la DO, mais obtiennent un taux de précision similaire. D’après la perspective homogène, le maintien des performances de DO s’expliquerait par le recrutement d’une stratégie de nature sémantique. Au niveau cérébral, nous observons une augmentation de l’asymétrie intra-hémisphérique gauche des régions temporo-pariétales chez les personnes âgées, ainsi qu’un transfert de la connectivité normalement observée du gyrus frontal inférieur (GFI) gauche avec le gyrus temporal latéral au gyrus temporal médial gauche. D’après la perspective hétérogène, le maintien des performances de DO s’expliquerait par l’utilisation d’une stratégie de nature exécutive, reflétée par une réduction de l’asymétrie inter-hémisphérique frontale chez les personnes âgées dont les temps de réponse de DO sont courts. Par ailleurs, nous proposons que l’encodage lexico-phonologique module également le taux de précision de DO, via la connectivité effective entre le GFI gauche et le gyrus temporal supérieur gauche. Enfin, nous observons une relation significative entre la fréquence de participation aux activités sociales, notamment collectives, et les performances de DO. Cette relation est partiellement médiée au niveau cérébral par l’activité du gyrus frontal supérieur médian gauche, via un mécanisme de réserve neurale. Sur la base de nos résultats, nous proposons un modèle neurocognitif des stratégies de récupération et de sélection de l’information lexicale, utilisant une approche multimodale et plurifactorielle du vieillissement sain. / Despite increased difficulties to find words in the daily life, older adults show preserved object naming performances when compared to younger ones. This suggests a supplementary recruitment of compensatory strategies in order to retrieve and select words. In this research work, we have used a multimodal methodological approach to evaluate the nature of these strategies, by using an object naming task. Specifically, we have evaluated these strategies in terms of mechanisms of cerebral reorganization. We were also interested to know how these strategies are modulated by the frequency of social activities, considered as a factor of cognitive reserve. This thesis work is composed of five studies performed under a homogeneous (effect of age) and a heterogeneous (effect of performance) perspective. Based on results, we suggest that aging is associated with multiple compensatory mechanisms to maintain a correct level of performance. Specifically, according to the homogeneous perspective, we consider that preserved object naming performances in older adults might be explained by the use of a semantic strategy. Indeed, in older compared to younger adults and at a cerebral level, we observed increased left hemispheric asymmetry with significant recruitment of the temporo-parietal regions. In addition, the inferior frontal gyrus (IFG) that is connected to the lateral temporal cortex in younger adults, seems to “switch” its connectivity toward the left medial temporal gyrus in older adults. In addition, according to the heterogeneous perspective, preserved object naming performances in older adults can be also explained by the use of an executive strategy, reflected by reduced inter-hemispheric asymmetry of frontal regions, specifically in more performant older adults (with shorter response latencies). Furthermore, we suggest that lexico-phonological processes mediate naming accuracy as reflected by the increased connectivity from the left IFG to the left superior temporal gyrus. A final result that we report in this work indicates that the frequency of participation to group social activities correlates to naming performance in older adults. This relation is partially mediated by the left superior medial frontal gyrus and is assimilated to a neural reserve mechanism. Overall, based on our findings, we propose a neurocognitive model of lexical retrieval and selection strategies in normal aging, based on a multimodal dataset and a multifactorial approach.

Objectives: The purpose of this thesis is to explore the associations between childhood cognitive abilities assessed at age 8 and health and socioeconomic outcomes at age 29-36 in extremely low birth weight survivors (ELBW, <1000g). Methods: Using data from the McMaster Extremely Low Birth Weight Cohort Study, Study 1 explores the influence of overall intelligence, fluid intelligence, and language abilities on the prevalence of lifetime major depressive disorder in ELBW survivors and normal birth weight comparison subjects. Study 2 examines the mediating role of overall intelligence, fluid intelligence, language abilities, quantitative reasoning, and academic achievement on the association between being born at ELBW and socioeconomic outcomes at age 29-36. The final study examines the moderating role of childhood cognitive functioning on links between postnatal psychosocial adversity and adult personal earnings in ELBW survivors. Results: Results from Study 1 suggest that childhood cognitive abilities do not influence the onset of major depressive disorder in ELBW survivors, but are protective against depression in normal birth weight individuals. Study 2 suggests that childhood cognitive abilities partially mediate the association between being born at ELBW and income attainment in adulthood, but not full time employment. Further, Study 2 suggests that this association is stronger in ELBW survivors who have neurosensory impairments. Results of Study 3 suggest that enhanced childhood cognitive functioning is not protective against postnatal psychological adversity in influencing income attainment, as those ELBW survivors with higher childhood intelligence and who suffered psychological adversity reported lower annual income at age 30. Conclusions: This thesis suggests that overall and specific cognitive abilities significantly influence adult outcomes in ELBW survivors and normal birth weight individuals. However, while cognitive reserve may not be protective against psychological adversity in ELBW survivors, early cognitive abilities are a critical indicator of socioeconomic attainment in this vulnerable population. / Thesis / Master of Science (MSc) / The following thesis explores the predictive role of childhood cognitive abilities on adult health and socioeconomic outcomes in extremely low birth weight survivors at age 29-36. Study 1 explores the influence of overall intelligence, fluid intelligence, and language abilities assessed at age 8 on the prevalence of lifetime major depressive disorder in extremely low birth weight survivors and normal birth weight comparison participants. Study 2 examines the mediating role of overall intelligence, fluid intelligence, language abilities, quantitative reasoning, and academic achievement on the association between being born at extremely low birth weight and socioeconomic outcomes at age 29-36. The final study examines the moderating role of childhood cognition on the association between postnatal psychosocial adversity and personal income attainment at age 30 in extremely low birth weight survivors. Overall, this body of work suggests that childhood cognitive abilities are an important contributor to adult outcomes in preterm survivors.