Conselho Nacional de Desenvolvimento Científico e Tecnológico / A população de idosos cresce rapidamente no Brasil. A prevalência de hipertensão arterial sistêmica (HAS) e distúrbios cognitivos é elevada nesta população. Testamos a hipótese de que a HAS reduz o desempenho cognitivos em idosos. Foram selecionamos idosos hipertensos e normotensos com idade &#8805; 60 < 80. O desempenho cognitivo foi avaliado pelo Cambridge Cognitive Examination Revised (CAMCOG-R), por subtestes do Wechsler Adult Intelligence Scale v.3 (WAIS III), além do Rey Auditory Verbal Learning Test (RAVLT), e o dos Trail Making Tests A/B (TMT-A/B). O desempenho cognitivo avaliado pelo escore global do CAMCOG-R e do QI estimado do WAIS III está reduzido nos idosos hipertensos mesmo quando controlado pela escolaridade, depressão, estado geral de saúde e qualidade de vida. O desempenho cognitivo em diversos domínios específicos controlados para a escolaridade, depressão, estado geral de saúde e qualidade de vida, e avaliados pelo CAMCOG-R, WAIS III, TMT-A e RAVLT também está reduzido nos idosos hipertensos. O presente estudo sugere que a HAS está associada ao declínio do desempenho cognitivo global em idosos. Notadamente, o desempenho das funções executivas está reduzido nos idosos hipertensos. Especula-se que a HAS seja um fator de risco para o declínio progressivo do desempenho cognitivo e, portanto, para o desenvolvimento de demência. / The elderly population is growing rapidly in Brazil. The prevalence of hypertension and cognitive disorders is high in this population. We tested the hypothesis that hypertension is associated with decreased cognitive performance in the elderly. We selected normotensive and hypertensive subjects aged &#8805; 60 <80 years old. Cognition was assessed through Cambridge Cognitive Examination Revised (CAMCOG-R), subtests of the Wechsler Adult Intelligence Scale v.3 (WAIS III), the Rey Auditory Verbal Learning Test (RAVLT), and the Trail Making Tests A/B (TMT-A/B). The cognitive performance assessed by the CAMCOG-R global score and the estimated WAIS III. QI is reduced in elderly hypertensives even when controlled for education, depression, health status and quality of life. The cognitive performance in diverse cognitive domains assessed through CAMCOG-R, WAIS III, TMT-A e RAVLT is also reduced in elderly hypertensives when contolled for education, depression, health status and quality of life. These results suggest that hypertension is associated with reduced global cognitive performance in eldely hypertensives. Notably, executive functions are reduced in eldely hypertensives. We speculate that hypertension might be a risk factor for the progressive decline in cognitive function and, therefore, for the development of dementia.

Vàrem estudiar la influència del gènere i l'edat sobre la memòria verbal i sobre variables motivacionals (expectatives i atribucions) que poden influir alhora en el rendiment cognitiu. Es va aplicar una prova de parells associats a 296 persones d'ambdós sexes, dividides en 4 grups d'edat (19-25, 30-40, 51-64 i 65-83). Es registraren també les expectatives i el rendiment percebut a cada part de la prova i les atribucions causals realitzades. Tant el gènere com l'edat influeixen sobre les variables estudiades. Es produeixen diferències de gènere que es manifesten de manera diferent segons l'edat, mostrant que les tendències tradicionals en la motivació de guany no desapareixen. Per altra banda, les diferències d'edat varien en funció del gènere: homes i dones afronten l'envelliment cognitiu de manera diferent, la qual cosa ens dona pautes per dissenyar i avaluar programes d'entrenament cognitiu dirigits a la gent gran. / Estudiamos la influencia del género y la edad sobre la memoria verbal y sobre variables motivacionales (expectativas y atribuciones) que, a su vez, pueden influir en el rendimiento cognitivo. Se aplicó una prueba de pares asociados a 296 personas de ambos sexos, divididas en cuatro grupos de edad (19-25, 30-40, 51-64 y 65-83). Se registraron también las expectativas y el rendimiento percibido en cada parte de la prueba y las atribuciones causales realizadas. Tanto el género como la edad influyen sobre las variables estudiadas. Se producen diferencias de género que se manifiestan de manera diferente según la edad, mostrando que las tendencias tradicionales en la motivación de logro no desaparecen. Por otra parte, las diferencias de edad varían en función del género: hombres y mujeres afrontan el envejecimiento cognitivo de manera diferente, lo que nos proporciona pautas para diseñar y evaluar programas de entrenamiento cognitivo dirigidos al colectivo de mayores. / We studied gender and age influence on verbal memory and motivational variables (expectancies and attributions) that can affect cognitive performance. A pair matching test was applied to a sample of 296 people of both sexes. We divided the sample into four groups (age 19-25, age 30-40, age 51-64, age 65-83). Expectancies, perceived performance and causal attributions were registered in each part of the test. Gender, as well as age, have an influence on the variables we examined. Gender differences occur in different ways for each age, showing that traditional tendencies in motivation for achievement do not disappear. On the other hand, age differences vary in function of gender: men and women face cognitive ageing in different ways, and this provides clues to design and evaluate cognitive training programs for the elderly.

Made available in DSpace on 2016-12-06T17:07:11Z (GMT). No. of bitstreams: 1 CarolinediBernardiLuft Dissertacao.pdf: 935107 bytes, checksum: 9ee03b1445d5ed4f5455ec9353279ace (MD5) Previous issue date: 2007-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This is a descriptive research whose objective was to investigate the relationship between stress, depression, cognitive performance and physical activity practice of elderly women, considering the intellectual activity level. This research had a quanti-quali approach. The sample was constituted by 80 physically independent elderly women of Florianopolis, selected in a non-probabilistic way by convenience or accessibility (COOLICAN, 2004). The elderly were considered as practicing, intermediate and non-practicing physical activity by means of structured questions about frequency, time and period of doing physical activity. The personal characteristics as economic class, income, self-evaluation of health, physical activity and leisure history, as well the intellectual activities were evaluated by means of a form, elaborated based on the questionnaire developed by Andrade (2001). The stress was measured by the Perceived Stress Scale of Cohen, Karmack and Mermelstein (1983). The depression was assessed through the Geriatric Depression Scale (GDS-15) developed by Yesavage et al. (1983). All these tests were applied by interview, being used in this research the elderly personal accounts, which were done spontaneously during the data collection. The cognitive performance was evaluated through the Mini-Mental State Evaluation (FOLSTEIN et al., 1978), which measures the overall cognitive capacity, and through a cognitive evaluation battery, CogState, internationally validated and constituted by a set of tests that measure simple and choice reaction time, working memory, short-term memory and sustained attention (DARBY, 2004). The data was treated by descriptive and inferential statistics, observing the normality of distribution. The personal accounts analysis was oriented by hermeneutic-dialectics synthesized by Minayo (2004). The results demonstrated that the majority of the elderly women is practicing physical activity, but they not used to practice it in the past, mainly because of labour conditions. The elderly who had practiced physical activity in the past have higher economic class than the ones who had not practiced or had a heavy work. There was not a relation between current physical activity practice, economic class and income. There was no difference in stress, depression and cognitive performance between the practicing, intermediate and not practicing physical activity. The occurrence of emotional problems, as the children s death, financial difficulties or serious ill, was determinant of the stress and depression level (p<0,001). The intellectual activity level was determinant of the cognitive performance of the elderly on the majority of tasks, including the overall cognitive capacity, choice reaction time, working memory and short-term memory. There was not any interactive effect of physical activity practice with the study variables. The personal accounts demonstrated other important elements for the analyses, as the economic class. It was observed that the current and past economic class is a determinant factor of several investigated questions. It was concluded that the physical activity is not determinant of stress, depression and cognitive performance of the elderly and that it is necessary to redirect the research and actions in order to consider the history, context and perception of the study population. / Esta é uma pesquisa descritiva que teve como objetivo investigar as relações entre estresse, depressão, desempenho cognitivo e prática de atividade física de idosas, considerando o nível de atividade intelectual. A abordagem desta pesquisa foi quanti-quali . A amostra foi constituída por 80 idosas fisicamente independentes de Florianópolis, participantes de diferentes grupos de idosos, selecionadas de forma não-probabilística por conveniência ou acessibilidade (COOLICAN, 2004). As idosas foram caracterizadas como praticantes, intermediárias e não praticantes de atividade física através de questões estruturadas sobre a freqüência, duração e período de realização de atividade física. As características pessoais como classe econômica, renda mensal, auto-avaliação da saúde, histórico de atividade física e lazer, bem como as atividades intelectuais foram avaliadas por meio de um formulário elaborado com base no questionário desenvolvido por Andrade (2001). O estresse foi mensurado por meio da Escala de Estresse Percebido de Cohen, Karmack e Mermelstein (1983). A depressão foi avaliada através da Escala de Depressão em Geriatria (GDS-15) desenvolvida por Yesavage et al. (1983). Todos estes testes foram aplicados em forma de entrevista, sendo utilizados os depoimentos feitos espontaneamente durante as coletas de dados. O desempenho cognitivo foi avaliado através do Mini-Exame do Estado Mental (FOLSTEIN et al., 1978), que mensura capacidade cognitiva geral, e de uma bateria de avaliação cognitiva computadorizada validada internacionalmente, que consta de um conjunto de testes que mensuram tempo de reação simples e de escolha, memória de trabalho e de curto prazo e atenção concentrada (DARBY, 2004). Os dados foram tratados com estatística descritiva e inferencial, observando a normalidade da distribuição. A análise dos depoimentos das idosas foi orientada pela hermenêutica-dialética sintetizada por Minayo (2004). Os resultados demonstraram que a maioria das idosas é praticante de atividades física, mas não praticavam no passado, principalmente por causa das condições de trabalho. As idosas que foram praticantes de atividade física no passado são de classe econômica mais alta do que as não praticantes e as que trabalhavam pesado. A prática de atividade física atual não foi relacionada com classe econômica ou renda mensal. Não houve diferença no estresse, depressão e desempenho cognitivo das idosas praticantes, intermediárias e não praticantes de atividade física. A ocorrência de problemas emocionais, como a morte de filhos, dificuldades financeiras e doença grave, foi determinante no nível de estresse e depressão (p<0,001). O nível de atividade intelectual foi determinante no desempenho cognitivo das idosas na maioria das tarefas, incluindo a capacidade cognitiva geral, tempo de reação de escolha, memória de trabalho e de curto prazo. Não houve interação entre atividade física e nenhuma das variáveis. Os depoimentos demonstraram outros elementos que devem ser considerados nas análises, tais como a classe econômica. Observou-se que a classe econômica, atual e no passado, é um fator determinante em várias das questões investigadas. Conclui-se que a atividade física isoladamente não tem um papel determinante no estresse, depressão e no desempenho cognitivo das idosas e que é fundamental redirecionar as pesquisas e as ações considerando a história, o contexto e a percepção da população em estudo.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A população de idosos cresce rapidamente no Brasil. A prevalência de hipertensão arterial sistêmica (HAS) e distúrbios cognitivos é elevada nesta população. Testamos a hipótese de que a HAS reduz o desempenho cognitivos em idosos. Foram selecionamos idosos hipertensos e normotensos com idade &#8805; 60 < 80. O desempenho cognitivo foi avaliado pelo Cambridge Cognitive Examination Revised (CAMCOG-R), por subtestes do Wechsler Adult Intelligence Scale v.3 (WAIS III), além do Rey Auditory Verbal Learning Test (RAVLT), e o dos Trail Making Tests A/B (TMT-A/B). O desempenho cognitivo avaliado pelo escore global do CAMCOG-R e do QI estimado do WAIS III está reduzido nos idosos hipertensos mesmo quando controlado pela escolaridade, depressão, estado geral de saúde e qualidade de vida. O desempenho cognitivo em diversos domínios específicos controlados para a escolaridade, depressão, estado geral de saúde e qualidade de vida, e avaliados pelo CAMCOG-R, WAIS III, TMT-A e RAVLT também está reduzido nos idosos hipertensos. O presente estudo sugere que a HAS está associada ao declínio do desempenho cognitivo global em idosos. Notadamente, o desempenho das funções executivas está reduzido nos idosos hipertensos. Especula-se que a HAS seja um fator de risco para o declínio progressivo do desempenho cognitivo e, portanto, para o desenvolvimento de demência. / The elderly population is growing rapidly in Brazil. The prevalence of hypertension and cognitive disorders is high in this population. We tested the hypothesis that hypertension is associated with decreased cognitive performance in the elderly. We selected normotensive and hypertensive subjects aged &#8805; 60 <80 years old. Cognition was assessed through Cambridge Cognitive Examination Revised (CAMCOG-R), subtests of the Wechsler Adult Intelligence Scale v.3 (WAIS III), the Rey Auditory Verbal Learning Test (RAVLT), and the Trail Making Tests A/B (TMT-A/B). The cognitive performance assessed by the CAMCOG-R global score and the estimated WAIS III. QI is reduced in elderly hypertensives even when controlled for education, depression, health status and quality of life. The cognitive performance in diverse cognitive domains assessed through CAMCOG-R, WAIS III, TMT-A e RAVLT is also reduced in elderly hypertensives when contolled for education, depression, health status and quality of life. These results suggest that hypertension is associated with reduced global cognitive performance in eldely hypertensives. Notably, executive functions are reduced in eldely hypertensives. We speculate that hypertension might be a risk factor for the progressive decline in cognitive function and, therefore, for the development of dementia.

De nombreuses études se sont intéressées aux effets délétères de la ménopause dans l’augmentation du risque de maladies cardiovasculaires et de troubles cognitifs. La chute des concentrations en hormones sexuelles liée à la ménopause impacte la pression artérielle, premier acteur responsable dans l’augmentation de la prévalence des maladies cardiovasculaires et des troubles cognitifs. Dans la population masculine, l’activité physique et ses effets notamment hypotenseurs apparaissent comme une stratégie non pharmacologique hautement efficace dans le maintien de la santé cardiovasculaire et cognitive. En revanche, les effets bénéfiques d’un mode de vie physiquement actif sur la pression artérielle, la santé vasculaire et la santé cognitive ne sont pas encore globalement admis chez les femmes post-ménopausées. Par conséquent, l'objectif de cette thèse était d'étudier l'impact de la ménopause sur la pression artérielle, les facteurs qui la régulent et les fonctions cognitives chez des femmes physiquement actives. A partir de la littérature existante, nous avons formulé l’hypothèse générale que la pression artérielle et les fonctions cognitives seraient préservées chez femmes post-ménopausées (stade + 1 de la classification STRAW+10) physiquement actives (≥150 min/sem d’activité physique à intensité modérée ou ≥ 75 min/sem d’activité physique à intensité vigoureuse) par rapport à des femmes pré-ménopausées (stade -3 de la classification STRAW+10) physiquement actives. Nous avons également formulé l’hypothèse que les marqueurs de santé vasculaires seraient préservés chez ces femmes post-ménopausées physiquement actives par rapport au groupe de femmes pré-ménopausées physiquement actives. Une revue de littérature et deux études transversales ont été réalisées pour vérifier ces hypothèses. Notre revue de littérature a mis en évidence : L’effet de la privation d'hormones sexuelles sur les mécanismes physiologiques impliqués dans l'augmentation de la pression artérielle à la ménopause. L'effet bénéfique de l’activité physique dans la prévention et le traitement de l'hypertension chez les femmes ménopausées. Les limites actuelles de la littérature scientifique quant aux effets bénéfiques de l’activité physique sur les mécanismes physiologiques régulant la pression artérielle. Nos études expérimentales ont permis de conclure que : Les femmes post-ménopausées physiquement actives ont des valeurs moyennes de pressions artérielles (systolique et diastolique) et des marqueurs vasculaires (rigidité artérielle, fonction endothéliale, sensibilité du baroréflexe) préservés par rapport aux femmes pré-ménopausées physiquement actives. Ces mêmes femmes post-ménopausées physiquement actives performent aussi bien que leurs homologues pré-ménopausées aux tests cognitifs évaluant la vitesse de traitement et les fonctions exécutives notamment pour les composantes inhibition et alternance. En revanche, elles performent moins bien que le groupe pré-ménopausées pour les tests évaluant la mémoire de travail. Cette thèse montre donc que d’être physiquement actif a des effets positifs sur la pression artérielle et les fonctions vasculaires des femmes en début de ménopause. Cependant cela ne permet pas de limiter totalement la baisse de la performance cognitive, notamment dans les domaines cognitifs évaluant les fonctions exécutives (mémoire de travail). Nous concluons que d’être physiquement actif permet de compenser certaines conséquences vasculaires, mais pas certaines conséquences cognitives associées à la transition ménopausique. / Numerous studies have focused on the deleterious effects of menopause that result in a greater risk of cardiovascular diseases and cognitive disorders. The fall in sex hormone concentrations associated with menopause increases blood pressure, which is the main factor involved in the increased prevalence of cardiovascular diseases and cognitive disorders. In males, the hypotensive effects of physical activity are a highly effective non-pharmacological strategy for maintaining cardiovascular and cognitive health. In contrast, the beneficial effects of a physically active lifestyle on blood pressure, vascular health, and cognitive health are not yet generally accepted in post-menopausal females. Therefore, the aim of this thesis was to study the effect of menopause on blood pressure, its regulating factors and cognitive function in physically active females. Based on the existing literature, we formulated the general hypothesis that blood pressure and cognitive functions would be preserved in physically active (≥150 min/week of moderate intensity physical activity or ≥75 min/week of vigorous intensity physical activity) post-menopausal females (stage +1 of the STRAW+10 classification) compared with physically active pre-menopausal females (stage -3 of the STRAW+10 classification). We also hypothesized that markers of vascular health would be preserved in the physically active post-menopausal group compared with the physically active pre-menopausal group. A literature review and 2 cross-sectional studies were performed to test these hypotheses. Our literature review highlighted: o The effect of sex hormone deprivation on the physiological mechanisms involved in increased blood pressure during menopause. The beneficial effect of physical activity in the prevention and treatment of hypertension in post-menopausal females. o The current knowledge gaps of the scientific literature regarding the beneficial effects of physical activity on the physiological mechanisms regulating blood pressure. Our experimental studies concluded that: o Physically active post-menopausal females have preserved mean values of systolic and diastolic blood pressures and physiological mechanisms involved in blood pressure regulation (arterial stiffness, endothelial function, baroreflex sensitivity) compared with physically active pre-menopausal females. o Physically active post-menopausal females perform as well as their pre- menopausal counterparts in cognitive tests evaluating processing speed and executive functions, particularly for the inhibition and alternation components. However, they performed worse than the pre-menopausal group on tests assessing working memory. Taken together this thesis shows that being physically active has positive effects on blood pressure and vascular function in early post-menopausal females. However, a physically active lifestyle does not completely limit the decline in cognitive performance, especially in cognitive domain assessing executive functions (working memory). We conclude that being physically active compensates for some vascular consequences, but not all cognitive consequences associated with the menopausal transition.

La leucémie lymphoblastique aiguë (LLA) est le cancer le plus fréquent chez les enfants. Malgré le fait que plus de 80% des enfants atteints de LLA sont aujourd'hui guéris de leur maladie, ce succès a toutefois un prix élevé, car l’exposition aux médicaments cytotoxique et/ou à l’irradiation pendant une période vulnérable du développement de l’enfant peut entraîner des conséquences à long terme. En effet, environ 60% des enfants ayant survécu à une LLA devront vivre avec des problèmes de santé liés au traitement, également appelés effets indésirables tardifs (late-adverse effects, LAEs). Parmi ces derniers, on notera des problèmes métaboliques, l’ostéoporose, une altération des fonctions cognitives ou cardiaques, ainsi que la dépression et l’anxiété. Si certains survivants ne présentent aucune de ces complications, d'autres peuvent en avoir plusieurs. Différents facteurs peuvent contribuer à cette variabilité, notamment le traitement reçu, les caractéristiques de la maladie, les habitudes de vie et, surtout, la constitution génétique du patient. Ce projet s'est concentré sur les biomarqueurs génétiques permettant d'identifier les individus les plus susceptibles de souffrir de LAEs. Récemment, une étude exhaustive (évaluations cliniques, psychosociales et biochimiques) s’est déroulée au CHU Sainte-Justine pour caractériser chacune de ces morbidités chez 250 survivants de la LLA de l'enfant (cohorte PETALE). De plus, on a obtenu le profil génétique de chaque participant. Nous avons utilisé cet ensemble de données et des outils statistiques et bio-informatiques pour réaliser des études d'association comparant la fréquence des variants génétiques chez les survivants ayant développé ou non des LAEs; en particulier, les complications cardiovasculaires et neurocognitives, ainsi que les troubles de l'humeur tels que l'anxiété et la dépression. D'autres facteurs de risque tels que les caractéristiques de traitement et/ou de la leucémie ont été pris en compte lors de l'analyse pour dériver les meilleurs prédicteurs génétiques. Ainsi, en utilisant l'approche des gènes candidats, nous avons identifié les variants communs des gènes MTR, PPARA, ABCC3, CALML5, CACNB2 et PCDHB10 qui étaient associés à des déficits de performance des tests neurocognitifs, tandis que les variants des gènes SLCO1B1 et EPHA5 étaient associés à l'anxiété et à la dépression. Deux variants, rs1805087 dans le gène MTR et rs58225473 dans le gène CACNB2 sont particulièrement intéressants, car ces associations ont été validées dans la cohorte de réplication SJLIFE (St. Jude Children's Research Hospital, Memphis, USA). Les analyses d'association ont été complémentées par une étude d'association à l'échelle de l'exome, qui a identifié plusieurs gènes supplémentaires comme des modulateurs potentiels du risque de développer des complications neurocognitives liées au traitement (gènes AK8 et ZNF382), ainsi que l'anxiété et la dépression (gènes PTPRZ1, MUC16, TNRC6C-AS1, APOL2, C6orf165, EXO5, CYP2W1 et PCMTD1). Le variant rs61732180 du gène ZNF382 a ensuite été validé dans la cohorte de réplication SJLIFE. Également, nous avons effectué des analyses d’association concernant les complications cardiaques liées au traitement qui ont identifié plusieurs nouveaux marqueurs associés à ces complications dans les gènes TTN, NOS1, ABCG2, CBR1, ABCC5, AKR1C3, NOD2 et ZNF267. De plus, nous avons résumé les connaissances actuelles sur les marqueurs pharmacogénomiques qui ont été associés aux effets de cardiotoxicités, induites par les anthracyclines, qui affectent les patients atteints de cancer pédiatrique. Nous avons également inclus un aperçu de l'applicabilité des résultats rapportés, notamment ceux qui ont été validés dans la cohorte PETALE. Par ailleurs, nous nous sommes intéressés aux complications qui surviennent après une greffe de cellules souches hématopoïétiques. Nous avons appliqué des approches bio-informatiques et statistiques similaires pour obtenir un profil plus complet de la composante génétique derrière ces complications potentiellement mortelles. Ainsi, une étude d'association à l'échelle de l'exome a été réalisée dans une cohorte de patients pédiatriques subissant une greffe de cellules souches hématopoïétiques après un régime de conditionnement contenant du busulfan. Nous avons identifié de nouvelles variations génétiques conférant un risque plus élevé de syndrome d'obstruction sinusoïdale (notamment dans les gènes UGT2B10, BHLHE22, et KIAA1715) et de maladie aiguë du greffon contre l'hôte (dans les gènes ERC1, PLEK, NOP9 et SPRED1), qui pourraient être utiles pour des stratégies personnalisées de prévention et de traitement. Ces travaux contribuent à la compréhension de l'influence des facteurs génétiques sur le risque de développer des complications liées au traitement, tant au cours du traitement qu'à long terme. De plus, les marqueurs génétiques signalés ainsi que d'autres facteurs de risque connus peuvent conduire à des modèles de prédiction identifiant les patients à risque accru de ces complications. / Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Even though more than 80% of children with ALL are now cured of their disease, this success comes at a high price as exposure to cytotoxic drugs and/or radiation during a vulnerable period of child development may have long-term consequences. In fact, approximately 60% of children who survive ALL will have to live with treatment-related health problems, also called late-adverse effects (LAEs). These include metabolic problems, osteoporosis, impaired cardiac or cognitive functions, as well as depression and anxiety. While some survivors do not have any of these complications, others may have more than one. Different factors can contribute to this variability, in particular, the treatment received, the characteristics of the disease, the lifestyle, and, above all, the genetic makeup of the patient. This project focused on genetic biomarkers capable of identifying the individuals most likely to suffer from LAEs. Recently, an exhaustive study (clinical, psychosocial, and biochemical evaluations) took place at Sainte-Justine University Health Center (Montreal, Canada), with the goal to characterize each of these morbidities in 250 survivors of childhood ALL (PETALE cohort). In addition, the genetic profile of each participant was obtained, and we used statistical and bioinformatics tools to perform association studies on this dataset in order to compare the frequency of genetic variants in survivors with or without LAEs. We evaluated cardiovascular and neurocognitive complications, as well as mood disorders such as anxiety and depression. Other risk factors, such as treatment and/or leukemia characteristics were also considered during the analysis to derive the best genetic predictors. Thus, using the candidate gene approach, we identified common variants in the MTR, PPARA, ABCC3, CALML5, CACNB2, and PCDHB10 genes that were associated with deficits in neurocognitive tests performance, whereas variants in the SLCO1B1 and EPHA5 genes were associated with anxiety and depression. Two variants, rs1805087 in the MTR gene and rs58225473 in the CACNB2 gene, are of particular interest since these associations were validated in an independent SJLIFE replication cohort (St. Jude Children's Research Hospital, Memphis, USA). The association analyses were complemented by an exome-wide association study, which identified several additional genes as potential modulators of the risk of developing treatment-related neurocognitive complications (genes AK8 and ZNF382), as well as anxiety and depression (genes PTPRZ1, MUC16, TNRC6C-AS1, APOL2, C6orf165, EXO5, CYP2W1, and PCMTD1). Variant rs61732180 in the ZNF382 gene was further validated in the replication SJLIFE cohort. To a great extent, we performed association analyses regarding treatment-related cardiac complications which identified several novel markers associated with these toxicities in the TTN, NOS1, ABCG2, CBR1, ABCC5, AKR1C3, NOD2, and ZNF267 genes in survivors of childhood ALL. In addition, we summarized the current knowledge on pharmacogenomic markers related to anthracycline-induced cardiotoxicity affecting pediatric cancer patients. We also included a brief overview of the applicability of reported findings to the PETALE cohort, validating several of them. Besides, we were interested in the complications that arise after a hematopoietic stem cell transplantation. We applied similar bioinformatics and statistical approaches to gain a more complete insight into the genetic component behind these life-threatening complications. Thus, an exome-wide association study was performed in a cohort of pediatric patients undergoing hematopoietic stem cell transplantation following a conditioning regimen containing busulfan. Our results identified new genetic variations conferring a higher risk of sinusoidal obstruction syndrome (notably in the UGT2B10, BHLHE22, and KIAA1715 genes) and acute graft-versus-host disease (ERC1, PLEK, NOP9, and SPRED1 genes), which could be useful for personalized prevention and treatment strategies. This work contributes to the understanding of the influence of genetic factors on the risk of developing treatment-related complications, both during treatment and in the long term. Furthermore, the reported genetic markers along with other known risk factors can lead to prediction models identifying patients at increased risk for these complications.