Alzheimer's disease (AD) is an increasing problem in modern society, both with regards to public health and cost of care. The causes of AD are not yet fully understood, and there is no cure or inhibiting drug. The aim of this thesis is to investigate the association between the bile acid profile as an indicator of dysbiosis and AD and mild cognitive impairment (MCI) using machine learning algorithms. The hypothesis that bile acid data can be used to predict AD or MCI at the time of diagnosis has been tested, and could not be confirmed. Somewhat better test results were obtained for the transition from normal cognitive function to MCI and from MCI to AD over time. Limitations relevant for this study included the possible uncertainties in the diagnostic patient data as well as in the relationship between bile acids and dysbiosis. The results from transitions in patient's diagnosis could warrant further research on the relationship between the bile acid profile or dysbiosis and changes in cognitive function. We suggest such research is conducted with more sophisticated models. / Alzheimers sjukdom (AD) är ett viktigt och ökande problem i dagens samhälle, både vad gäller folkhälsan och kostnaderna för samhället. Orsakerna bakom AD är än idag inte helt utredda och det finns inget botemedel eller bromsmedicin. Målet med den här studien är att undersöka sambandet mellan gallsyraprofilen som en indikator på dysbios och AD och mild kognitiv störning (MCI) med hjälp av maskininlärningsalgoritmer. Hypotesen att gallsyraprofilen kan användas för att förutsäga AD eller MCI vid diagnostillfället har studerats och kunde inte fastställas. Något bättre resultat erhölls vad gäller övergången från normal kognitiv funktion till MCI och från MCI till AD över tid. Begränsningar som är relavanta för studien inkluderar möjlig osäkerhet vad gäller diagnosen och även vad gäller sambandet mellan gallsyraprofilen och dysbios. Resultaten från förändringen i patienters diagnos kan vara en grund för fortsatt forskning om samband mellan gallsyraprofilen eller dysbios och förändringar i kognitiv funktion. Vi föreslår att mer sofistikerade modeller används för sådan forskning.

In assistive technology, there are mainly two different users that needs to be taken into account when developing products. The first, and most important, is the end-user who requires the product in order to function and live a normal life. The second is the support person who, for some products, needs to assist the end-user by preparing it to be used. This report presents the master thesis project conducted by Mattias Bygge and Sofie Strand at KTH Royal Institute of Technology in Stockholm. The client was Abilia, a company that research, develop, manufacture and sell assistive technology to people with impairments. This main goal of this project was to redesign a cognitive planning board. The product is used as a visual aid by people who has difficulties in planning daily activities and keeping track of time. In order to develop the product in a suitable way, a literature study and interviews with Abilia’s employees laid the foundation for the user studies that were conducted with end-users and support people. Several concepts were generated and five were evaluated against the original product and presented to the company. The two concepts that received the highest ranking, (1) Extra Hours and (2) Extra Hours Bistable, were further investigated and were eventually developed into one single hybrid concept. The final design proposal is Day Master, a flexible planning board intended for people with a cognitive impairment that impedes their ability to plan daily activities and keep track of time. The product visually displays time and weekdays by using coloured LED lights, which support people may program without difficulty to fit the end-user’s preference. The amount of hours is changeable with a range of 12-18 hours of daytime and with the remaining hours distributed to night-time. The accessories that have been developed for this products are a simple protective cover, and two holders, one for images and one for whiteboard markers. All accessories attaches to the planning board with magnets. / I hjälpmedelsteknologi är det fler än en användare som man måste ta hänsyn till när man utvecklar produkter. Den första och viktigaste är slutanvändaren som är den som behöver produkten i vardagen för att kunna leva ett någorlunda normalt liv. Den andra är stödpersonen som i många fall är den som förbereder produkten för användning av slutanvändaren. Denna rapport presenterar masterexamensarbetet utfört av Mattias Bygge och Sofie Strand på KTH Kungliga Tekniska Högskola i Stockholm. Kunden för projektet var Abilia, ett företag som utvecklar, tillverkar, och säljer hjälpmedel till personer med funktionsnedsättning. Målet med detta projekt var att omdesigna deras kognitiva planeringstavla. Produkten används som ett visuellt hjälpmedel av personer som har problem med tidsuppfattning och planering av aktiviteter. Projektet inleddes genom en literaturstudie och intervjuer med personal på Abilia. Detta lade grunden för användarstudierna där både slutanvändare och stödpersoner deltog. Utifrån användarstudierna så genererades ett flertal koncept varav fem stycken evaluerades mot original produkten och som presenterades för företaget under en delpresentation. De två koncept som erhöll högsta ranking i evalueringen var (1) Extra Hours och (2) Extra Hours Bistable. Koncepten undersöktes ytterligare och kom slutligen att kombineras till ett gemensamt koncept. Det slutgiltiga designförslaget är Day Master, en flexibel planeringstavla som riktar sig mot personer med en kognitiv funktionsnedsättning som försvårar för dem att hålla koll på tiden och planera aktiviteter. Produkten visar tid och veckodagar visuellt med hjälp av färgade LED lampor som stödpersonerna lätt och intuitivt kan programmera för att passa slutanvändarens individuella behov. Day Master ger möjligheten att själv bestämma antalet timmar som distribueras mellan dag och natt. Den har ett spann på 12-18 timmar för dagtid och återstående timmar läggs på natttid. Tillbehören som har utvecklats för denna produkt är ett enkelt magnetiskt plastskydd och två stycken olika ställ, ett för bilder och ett för whiteboardpennor. Alla tillbehör fästs på whiteboardtavlan med hjälp av magneter.

Syftet med denna studie är att undersöka hur professionella som är verksamma inom socialtjänst, äldrevård och HVB-hem arbetar med individer som visar tecken på kognitiv svikt, demens och alkoholmissbruk. Datainsamlingsmetoden utgjordes av semistrukturerade intervjuer. Sex (6) intervjuer genomfördes totalt och transkriberades sedan ordagrant. Det insamlade materialet analyserades sedan genom kvalitativ innehållsanalys. Det analyserade materialet tolkades sedan genom den socialekologiska systemteorin. Vissa delar av resultatet från intervjuerna visar att kunskapsbristen inom området skapar olika förutsättningar för arbetsgruppen. Andra delar visade även positiva och negativa exempel på samverkan mellan olika verksamheter. Dessutom visade resultatet även hur politiska beslut och avsaknaden av evidens kan orsaka förändrade förutsättningar för de professionellas arbete. Sammanfattningsvis visade resultaten vikten av samverkan i en kontext där klientens behov kan erbjudas av flera olika verksamheter. Dessutom visade även resultatet hur verksamheterna påverkas av både kunskapsbrister och svårigheter med att samla in evidens. Det kan även föreligga ett behov att reflektera över tidigare socialt arbete för att förstå hur framtidens sociala arbete eventuellt kan förbättras. / The purpose of this study is to examine how professional employees working at social work offices and care homes experience possible opportunities and obstacles while working with individuals showing signs of both cognitive impairment, dementia and the misuse of alcohol. The method of which the material was collected was through semi-structured interviews. In total, six (6) interviews were conducted and later transcribed verbatim. The material was compiled through qualitative content analysis. The compiled material was then later analysed through the social ecological systematic theory. Some of the contents provided through the interviews showed a lack of knowledge regarding the work surrounding the group mentioned above. Other parts of the interview showed both positive and negative examples within cooperation between multiple organisations. The contents also gave examples of how the work is affected by political decisions and also obstructed by the lack of evidence surrounding the group. In conclusion, the results showed how crucial cooperation can be in a context where the afflicted is in need of several instances of help from several different organisations. Moreover, the results also showed a lack in both knowledge and the acquiring of evidence. There may also be a need to reflect on earlier social work to see how future social work can be improved.

Les symptômes neuropsychiatriques (SNP), des perturbations comportementales et psychologiques, surviennent fréquemment dans la démence de la maladie d’Alzheimer. En plus d’être un facteur de risque d’institutionnalisation précoce et de constituer une charge pour les aidants, ils peuvent aussi être associés à un déclin cognitif accéléré ou à des troubles cognitifs plus importants lorsqu’ils surviennent dans les stades pré-démentiels des maladies (avant ou pendant le trouble cognitif léger). Considérant la diversité des résultats d’études antérieures, la relation entre ces SNP, le déclin cognitif et la survenue/évolution des maladies neurodégénératives est encore pleine de mystères. En effet, il a pu être mis en évidence que la dépression, l’apathie, ou encore l’anxiété étaient des facteurs de risques de conversion en maladie d’Alzheimer, ou de déclin cognitif accéléré chez des individus ayant un trouble cognitif léger ou une cognition normale. Ils ont aussi pu être associés à des changements des structures ou du métabolisme cérébraux, limbiques et associatifs. Cependant, le rôle et la position exacte des SNP dans le décours temporel des maladies restent incertains : conséquences de la neurodégénérescence ? Conséquence psychologique de la survenue de troubles cognitifs ? Cause de troubles cognitifs par réorientation des ressources exécutives et comportementales ? Stade prodromal des maladies ? Conséquence d’une structure de personnalité antérieure ? Ce travail propose d’aborder différentes problématiques de recherches liées aux SNP, notamment leurs associations cognitives en fonction de facteurs démographiques, psychologiques ou psychiatriques dans différents stades de déclins cognitifs ; leurs associations neurostructurelles ou métaboliques cérébrales, en devis transversal, rétrospectif ou longitudinal. L’objectif étant de conforter certaines données de la littérature sur l’impact des SNP sur les performances cognitives et leur évolution dans le vieillissement normal et pathologique, et comprendre l’apport de certaines analyses prédictives et de facteurs de risques afin d’en dégager des pistes d’applications cliniques dans une visée d’anticipation du déclin cognitif. Pour cela, différentes bases de données sont traitées afin d’extraire différents types de variables d’intérêt (démographiques, neuropsychiatriques, neuropsychologiques, neuroimagerie, statuts génétiques et diagnostiques, facteurs psychologiques…). Au total, c’est près de 5000 participants qui ont été extraits et analysés au travers des différentes bases de données. Les principaux résultats ont permis de montrer : 1) des associations SNP/performances cognitives différentes entre les femmes et les hommes ; 2) des relations neurostructurelles différentes entre les SNP et les différents stades de déclin cognitif de la maladie d’Alzheimer ; 3) le rôle prédictif des SNP dans la conversion du trouble cognitif léger en maladie d’Alzheimer expliqué par l’altération des habiletés fonctionnelles des individus ; 4) des implications de traits de personnalité dans le déclin cognitif et cérébral chez des individus développant ou non démence de type Alzheimer. Ces données consolident les résultats de la littérature et soutiennent l’utilité de certains modèles statistiques et de prédictions dans l’établissement des facteurs de risques de déclin et l’estimation de l’importance du déclin basé sur ces facteurs, à la fois chez des individus cognitivement sains, et des individus à risque de développer une démence. / Neuropsychiatric symptoms (NPS), behavioral and psychological disturbances, occur frequently in Alzheimer's dementia. In addition to being a risk factor for early institutionalization and a burden to caregivers, they may also be associated with accelerated cognitive decline or greater cognitive impairment when they occur in the pre-dementia stages of the diseases (before or during mild cognitive impairment). Considering the diversity of results of previous studies, the relationship between these NPS, cognitive decline and the occurrence/evolution of neurodegenerative diseases is still full of mysteries. Indeed, it has been shown that depression, apathy, or anxiety were risk factors for conversion to Alzheimer's disease, or for accelerated cognitive decline in individuals with mild cognitive impairment or normal cognition. They could also be associated with changes in brain, limbic and associative structures or metabolism. However, the exact role and position of NPS in the temporal course of diseases remains uncertain: consequences of neurodegeneration? Psychological consequence of the onset of cognitive disorders? Cause of cognitive disorders by redirection of executive and behavioral resources? Prodromal stage of diseases ? Consequence of a previous personality structure? This work proposes to address different research issues related to NPS, in particular their cognitive associations according to demographic, psychological or psychiatric factors in different stages of cognitive decline; their neurostructural or cerebral metabolic associations, in crosssectional, retrospective or longitudinal specifications. The objective is to confirm certain data in the literature on the impact of NPS on cognitive performance and its evolution in normal and pathological aging, and to understand the contribution of certain predictive analyses and risk factors in order to identify avenues of clinical application with a view to anticipating cognitive decline. For this purpose, different databases are processed in order to extract different types of variables of interest (demographic, neuropsychiatric, neuropsychological, neuroimaging, genetic and diagnostic status, psychological factors...). In total, nearly 5000 participants were extracted and analyzed through the different databases. The main results showed: 1) different NPS/cognitive performance associations between women and men; 2) different neurostructural relationships between NPS and different stages of cognitive decline in Alzheimer's disease; 3) the predictive role of NPS in the conversion of mild cognitive impairment to Alzheimer's disease explained by the alteration of individuals' functional abilities; 4) implications of personality traits in cognitive and brain decline in individuals developing or not dementia of the Alzheimer’s type. These data consolidate the findings of the literature and support the utility of certain statistical and predictive models in establishing risk factors for decline and estimating the magnitude of decline based on these factors, both in cognitively healthy individuals, and individuals at risk of developing dementia.

No description available.

[pt] O Comprometimento cognitivo vascular subcortical (CCVs) caracteriza-se, do ponto de vista cognitivo, por déficits em funções executivas em seus estágios iniciais, levando a dificuldades funcionais precoces na população acometida. Contudo, dados da literatura indicaram que a condição é frequentemente subdiagnosticada, o que pode ser atribuído, dentre outras razões, à falta de instrumentos de rastreio acurados para a condição, cujas características clínicas diferem dos quadros neurodegenerativos. Esta escassez foi evidenciada pela revisão sistemática realizada como parte do presente trabalho. O Teste Breve de Memória e Funções Executivas (BMET) foi desenvolvido por Brookes e cols. (2012) especificamente para a detecção destes quadros clínicos. O objetivo desta dissertação foi discorrer sobre o CCVs e adaptar o BMET para o uso na população acima dos 60 anos do Brasil. Para tanto, seguiram-se etapas de tradução, avaliação de juízes de linguística e de neuropsicologia, avaliação por representante do público-alvo, retrotradução e, por fim, aplicação à amostra. Foi conduzido um estudo piloto para verificar a aplicabilidade e fornecer dados psicométricos preliminares do teste. Conclui-se que o BMET é de simples e rápida aplicação, podendo ser administrado por diferentes profissionais da saúde e possivelmente adequado à atenção primária em saúde. Considerando o contexto atual de um rápido envelhecimento populacional e do consequente aumento na prevalência de agravos associados às faixas etárias avançadas, tais como os transtornos neurocognitivos, é de grande relevância a detecção precoce do CCVs visando ao planejamento de intervenções e medidas de profilaxia secundária, contribuindo assim, para a qualidade de vida da população idosa. / [en] Subcortical Vascular Cognitive Impairment (sVCI) is characterized, upon a cognitive perspective, by the presence of dysexecutive function in its initial stages, leading to early functional difficulties for sufferers of this condition. However, data has indicated that it is often underdiagnosed, which could be attributed to the lack of accurate screening tools for the disorder. This shortcoming has been evidenced by a systematic review conducted as part of the current project. The Brief Memory and Executive Test (BMET) has been specifically developed by Brookes et al. (2012) for the detection of sVCI. This thesis aimed to discuss about sVCI and to adapt BMET for use in subjects over 60 years old from Brazil. For this purpose, consecutive stages, comprising translation, evaluation by experts in linguistics and neuropsychology, assessment by representant of the target population, retro-translation and, finally, application to an older sample, have been performed. A pilot study has been carried out to analyze the applicability and to draw preliminary information about psychometric properties of the scale. In conclusion, BMET has revealed to be easy and rapid to administer, feasible to be applied by different categories of health practitioners and possibly adequate for primary health settings. Considering the current context of a fast population aging and a rise in the prevalence of conditions associated with late-life, such as neurocognitive disorders, it is relevant to detect sVCI in its early stages, so that therapeutic and secondary preventive strategies could be planned, which could impact on the quality of lives of older population.

Les troubles cognitifs postopératoires sont fréquents après une chirurgie cardiaque, variant entre 26 % à 70 %. Bien que diverses hypothèses expliquent leur pathogenèse, la congestion veineuse représente une hypothèse prometteuse. Des études ont associé le délirium à des signes échographiques de congestion veineuse tels que la pulsatilité du Doppler de la veine porte et rénale. Détecter la congestion veineuse pourrait potentiellement prédire le trouble cognitif, facilitant ainsi sa gestion. Une technique prometteuse, mais peu explorée, est l’évaluation de la congestion veineuse par le Doppler de la veine fémorale. Les objectifs de ce mémoire sont : (1) synthétiser les évidences sur la relation entre le Doppler de la veine fémorale et la congestion veineuse chez les adultes ; et (2) caractériser l’existence d’une association entre les trouble cognitifs et le Doppler pulsatile de la veine fémorale après une chirurgie cardiaque. Afin d’atteindre ces objectifs, nous avons effectué une revue rapide de littérature portant sur la corrélation entre le Doppler de la veine fémorale et la congestion veineuse. De plus, nous avons complété une étude (NCT05038267) dont l’objectif secondaire était de déterminer la corrélation entre un Doppler anormal de la veine fémorale et le délirium. Les résultats ont montré une association entre la congestion veineuse et Doppler pulsatile de la veine fémorale, ainsi qu’entre les troubles cognitifs et le Doppler anormal de la veine fémorale. Toutefois, des études approfondies sont nécessaires. En conclusion, un lien entre le Doppler de la veine fémorale, la congestion veineuse, et les troubles cognitifs après une chirurgie cardiaque a été démontré. Ces observations ouvrent la voie à des recherches approfondies sur ce lien et à de potentielles applications cliniques et thérapeutiques. / Postoperative cognitive disorders are common after cardiac surgery, ranging from 26% to 70%. While various hypotheses explain their pathogenesis, venous congestion emerges as a promising hypothesis. Studies have linked delirium to ultrasound signs of venous congestion, such as pulsatility in the Doppler of the portal and renal veins. Detecting venous congestion could potentially predict cognitive disorders, thus facilitating their management. A promising yet underexplored technique is the assessment of venous congestion using the Doppler of the femoral vein. The objectives of this thesis are: (1) to synthesize evidence on the relationship between FV Doppler characteristics and venous congestion in adults; and (2) to characterize the existence of an association between cognitive disorders and pulsatility in femoral vein Doppler after cardiac surgery. To achieve these objectives, we conducted a rapid literature review focusing on the correlation between femoral vein Doppler and venous congestion. Additionally, we completed a study (NCT05038267) with the secondary objective of determining the correlation between abnormal femoral vein Doppler and delirium. The results showed an association between venous congestion and pulsatility in the FV Doppler, as well as between cognitive disorders and abnormal FV Doppler. However, in-depth studies are needed. In conclusion a connection has been demonstrated between femoral vein Doppler, venous congestion, and cognitive disorders after cardiac surgery. These findings open the way for in-depth research on this link and potential clinical and therapeutic applications.

L’apnée obstructive du sommeil (AOS) est l’un des troubles du sommeil les plus fréquents chez l’adulte et sa prévalence augmente avec l’âge. Elle se caractérise par des arrêts répétés de la respiration au cours du sommeil, menant à la présence de fragmentation du sommeil et à de l’hypoxémie intermittente. Lorsque non traité, ce trouble peut mener à diverses conséquences non négligeables sur la santé des individus qui en sont atteints, incluant sur la santé du cerveau. L’AOS est d’ailleurs de plus en plus reconnue comme étant un possible facteur de risque de déclin cognitif et de démence. Dans ce contexte, quelques études transversales ont caractérisé le volume de la substance grise cérébrale chez des adultes vieillissants atteints d’AOS, avec des résultats variables. En effet, certaines études ont noté de plus grands volumes de substance grise chez les personnes avec une AOS plus sévère, alors que d’autres ont retrouvé des plus petits volumes chez cette même population. Ce qui explique la variabilité entre les études demeure à ce jour mal compris, bien que certaines hypothèses aient émergé. Ainsi, cette thèse vise à évaluer l’association entre la sévérité de l’AOS et le volume de substance grise cérébrale chez des personnes d’âge moyen et âgées de manière transversale et longitudinale. La première étude de cette thèse se base sur des techniques de neuroimagerie afin d’évaluer les liens entre la sévérité de l’AOS et le volume de la substance grise cérébrale des sous-régions du lobe temporal médian, soit l’hippocampe, le cortex entorhinal et le cortex parahippocampique. Celles-ci ont été ciblées puisqu’elles peuvent être affectées tôt dans la progression de la pathologie de la maladie d’Alzheimer (MA). De plus, nous avons testé l’effet d’une correction de la portion d’eau libre sur les volumes cérébraux. Finalement, nous avions comme objectif de mieux comprendre si certaines caractéristiques démographiques ou cliniques de nos participants pouvaient avoir un impact sur les associations observées. Nous avons observé qu’une AOS plus sévère était associée à des volumes de substance grise plus grands de certaines sous-régions du lobe temporal médian (hippocampe et cortex entorhinal), mais seulement chez des groupes de participants spécifiques, soit les femmes, les participants plus âgés et ceux présentant un trouble cognitif léger de type amnésique. Le fait d’apporter une correction pour la portion d’eau libre aux volumes mesurés a rendu non significatives les associations observées. Il est donc possible que la présence accrue d’eau extracellulaire, suggérant de l’œdème cérébral, puisse expliquer la présence de plus grands volumes chez les participants présentant une AOS plus sévère. La deuxième étude visait quant à elle à évaluer les changements structurels des sous-régions du lobe temporal médian associés à la sévérité de l’AOS chez des personnes d’âge moyen et âgées sur une période d’environ 2 ans. Nous avons démontré que chez nos participants n’ayant pas utilisé un traitement pour l’AOS, la présence d’interaction entre la sévérité de l’AOS et l’âge permettait d’expliquer les changements annuels de volume de substance grise. De fait, les participants plus jeunes de notre échantillon (< 65 ans) avec une AOS plus sévère présentaient un plus grand taux de changement annuel de volume de substance grise, soulignant la présence d’hypertrophie dans ce sous-groupe. Ceci a été mis en lumière pour l’ensemble des sous-régions du lobe temporal médian. Chez les participants âgés entre 65 et 75 ans, aucune association entre la sévérité de l’AOS et les changements de volume au fil du temps n’a pu être soulignée. Les participants plus âgés (> 75 ans) avec une plus grande sévérité d’AOS présentaient quant à eux une plus grande atrophie au fil du temps dans certaines régions, soit l’hippocampe et le cortex entorhinal. Ces résultats supportent donc une hypothèse biphasique des changements au niveau de la substance grise cérébrale chez les gens présentant de l’AOS, avec une première phase caractérisée par des augmentations de volume chez les adultes plus jeunes, menant éventuellement à de l’atrophie chez les personnes plus âgées. Cette thèse permet d’avoir un portrait plus clair sur la nature des changements et des mécanismes impliqués dans l’association entre la sévérité de l’AOS et les volumes de substance grise. L’un des apports importants est l’utilisation d’une nouvelle méthodologie afin d’obtenir une portion d’eau libre, ce qui a permis de mieux comprendre l’apport potentiel de mécanismes pouvant sous-tendre les changements structuraux observés, notamment l’œdème cérébral. De plus, l’évaluation des caractéristiques individuelles des participants a permis d’expliquer partiellement les incongruences entre les études précédentes. Dans le cadre des études incluses dans cette thèse, nous avons observé des changements plus marqués chez les femmes. Nous avons également pu démontrer que l’âge des individus atteints d’AOS pouvait influencer significativement le patron de changements observés. Les résultats de cette thèse pourraient donc permettre de mieux cibler les personnes avec AOS qui pourraient le plus bénéficier d’un traitement pour maintenir leur santé cérébrale. / Obstructive sleep apnea (OSA) is one of the most common sleep disorders in adults, and its prevalence increases with age. It is characterized by repeated pauses in breathing during sleep, leading to sleep fragmentation and intermittent hypoxemia. If left untreated, this disorder can have numerous consequences, including on the brain’s health. OSA is increasingly recognized as a risk factor for cognitive decline and dementia. In this context, cross-sectional studies have characterized brain gray matter volume in aging adults with OSA, with variable results. Indeed, some studies have noted greater gray matter volumes in people with more severe OSA, while others have found smaller volumes in this same population. What explains the variability between studies remains poorly understood, although some hypotheses have emerged. Thus, this thesis aims to assess the association between OSA severity and cerebral gray matter volume in middle-aged and elderly individuals using cross-sectional and longitudinal designs. The first study in this thesis uses neuroimaging techniques to assess the links between OSA severity and cerebral gray matter volume of the medial temporal lobe subregions, i.e. the hippocampus, entorhinal cortex and parahippocampal cortex. These were chosen as they can be affected early in the progression of Alzheimer's disease (AD) pathology. We also corrected our brain volumes for free-water portion. Finally, we aimed to better understand whether certain demographic or clinical characteristics of our participants might have an impact on the associations observed. We noted that more severe OSA was associated with larger gray matter volumes in certain subregions of the medial temporal lobe (hippocampus and enthorinal cortex), but only in specific groups of participants: women, older participants and those with amnestic mild cognitive impairment. Correcting our volumes for free-water portion rendered the associations nonsignificant. It is therefore possible that the presence of extracellular water, suggestive of cerebral edema, could explain the presence of larger volumes in participants with more severe OSA. The second study aimed to assess longitudinal structural changes associated with OSA severity in middle-aged and elderly people over a period of around 2 years. We found that in participants who did not use treatment for OSA, the presence of interactions between OSA severity and age were associated with the annual changes in gray matter volume. Indeed, younger participants (< 65 years old) in our sample with more severe OSA showed a greater rate of annual change in gray matter volume, highlighting the presence of hypertrophy in this subgroup. This was underlined in all medial temporal lobe subregions. In participants aged between 65 and 75, no association between OSA severity and volume changes over time could be highlighted. Older participants (>75 years old) with greater OSA severity showed greater hippocampal and entorhinal cortex atrophy over time. These results therefore support a biphasic hypothesis of changes in cerebral gray matter in people with OSA, with an initial phase characterized by volume increases in younger adults, eventually leading to atrophy in older people. This thesis provides a clearer picture of the nature of the changes and mechanisms involved in the association between OSA severity and gray matter volumes. An important contribution is the use of a new methodology to obtain a free-water portion, which allows to better understand the potential contribution of mechanisms that may underlie the structural changes observed, notably cerebral edema. In addition, the assessment of participants' individual characteristics helped to partially explain incongruities between previous studies. Indeed, in the studies included in this thesis, we observed more marked changes in certain subgroups of participants, notably women. We were also able to demonstrate that the age of individuals with OSA could significantly influence the pattern of changes observed, either gray matter hypertrophy or atrophy. The results of this thesis could therefore make it possible to target specific subgroups of individuals suffering from OSA who may be at greater risk of displaying changes in gray matter structure, and thus promote screening and treatment when necessary.

This research examines narratives about the quality of everyday life with dementia. The aim of the study is to compare and contrast differing perspectives about the impact of ageing and dementia upon the lives of older people with dementia. A total of 50 interviews with six older people with dementia and ten family and paid carers were conducted over a two-year period. Narrative analysis was used to examine the content and structure of their accounts to understand their perspectives on what matters most to people living with dementia. This in-depth analysis enabled an exploration of different social concepts and narrative constructions that people draw upon in making sense of their experiences of caring and living with dementia. The analysis demonstrated that older people incorporate ageing and dementia into a continuing sense of self. Positive constructions of living with dementia involve the ability to lead a meaningful life that supports pre-existing social roles and relationships and active engagement within the family and community. The emphasis is on living an ordinary life while responding to the challenges associated with cognitive impairment and social stigma. For family and paid carers, perceptions of a meaningful life depend on how the identity of the older person with dementia is positioned relative to past social roles and relationships. Positive constructions assume continuity as opposed to focusing on disruption in the person’s identity and life. Carer perspectives are also influenced by how the person is perceived to conform to social standards of normality. The narratives of older people with dementia reflect their active struggle to find meaning in terms of realising their sense of self within a social world that largely defines them as different and out of the ordinary. The narratives of carers resonate with emotional difficulty, reflecting their struggle to make sense of a life that is not represented as essentially normal. These findings show that, for all, finding meaning in everyday life depends upon making sense of that life as normal and ordinary.

Introdução: A tomografia por emissão de pósitrons (PET) permite a avaliação in vivo de alvos moleculares em doenças neurodegenerativas, como a doença de Alzheimer (DA). A deposição de placa Beta-amiloide pode ser avaliada por PET 11C-PIB, enquanto o PET 18F-FDG é utilizado para avaliar o metabolismo da glicose cerebral, que pode ser um indicador de lesão neuronal e disfunção sináptica. Além disso, a captação cerebral precoce de radiofármacos de PETamiloide pode determinar o fluxo sanguíneo cerebral regional. Mais estudos correlacionando a fase inicial de perfusão do 11C-PIB (11C-pPIB) e 18F-FDG ainda são necessários, considerando que o fluxo sanguíneo e o metabolismo da glicose cerebral são geralmente acoplados em repouso e durante as ativações neuronais. Objetivo: Avaliar se existe concordância diagnóstica e/ou topográfica entre a imagem na fase de perfusão do 11C-PIB (11C-pPIB), obtida entre 0 e 10 minutos, e a imagem metabólica de PET 18F-FDG através da quantificação por SPM (Statistical Parametric Mapping) e por análise visual, em sujeitos com DA e CCLa comparados aos controles idosos saudáveis. Métodos: CAPEPesq: Nº1.454.598. Noventa e três sujeitos foram alocados em três grupos de acordo com o diagnóstico clínico: doença de Alzheimer (DA - n = 27); Comprometimento Cognitivo Leve amnéstico (CCLa - n = 39); Controle idosos saudáveis (n = 27), estes foram submetidos a exames de imagens de RM ponderada em T1 e de PET/CT. A PET/CT 18F-FDG foi realizada 30 minutos após a injeção do radiofármaco e a PET/CT 11C-pPIB foi adquirida imediatamente após a injeção do radiofármaco, e os primeiros 10 minutos da aquisição foram considerados na análise. Imagens de PET foram corrigidas para efeito de volume parcial e as imagens foram espacialmente normalizadas utilizando um modelo anatômico personalizado da própria amostra (template), para análise por Mapa Estatístico Paramétrico (SPM8). A análise visual e individual foi realizada por dois médicos nucleares com experiência na área, cegos em relação à identificação das imagens, seus respectivos radiofármacos e diagnóstico clínico. Eles foram solicitados a fornecer um diagnóstico e indicar uma classificação com base na inspeção visual das imagens de 18F-FDG e 11CpPIB, e também na avaliação individual dos mapas-t de SPM (análise baseada em voxel comparando um único sujeito do grupo DA com um grupo de controle cognitivamente normal). Resultados e Discussão: Na análise por SPM, o 11CpPIB mostrou menor captação difusa cortical do que 18F-FDG. Na análise entre grupos, há uma diferença na captação de 11C-pPIB e 18F-FDG, o que é esperado, uma vez que a biodistribuição é uma propriedade particular de cada biomarcador de PET. Na comparação do grupo DA em relação ao grupo controle, os indivíduos com DA apresentaram diminuição da captação de 11C-pPIB nas regiões temporo-límbicas: amígdala e hipocampo (E = esquerdo) P = 0,006, amígdala e hipocampo (D = direito) P = 0,023; giro parahipocampal (E) P = 0,008 (D) P = 0,015; temporal superior (E) P = 0,012 (D) P = 0,015. No 18F-FDG, houve diminuição da captação no grupo DA comparado ao grupo controle nas seguintes regiões: córtex do cíngulo posterior (E) P = 0,028; pré-cuneus (E) P= 0,029; giro temporal médio (E) P = 0,039; giro temporal inferior (E) P = 0,044. Na comparação do grupo CCLa em relação ao grupo controle, os indivíduos com CCLa apresentaram diminuição da captação de 11C-pPIB na região do giro parahipocampal (E) P = 0,012. Na identificação visual, 100% das imagens PET 18F-FDG e 99% das imagens PET 11C-pPIB foram corretamente identificadas. Na análise visual e individual, foram observadas reduções na captação de 11CpPIB envolvendo a região temporal medial nos indivíduos com DA que não foi detectada pelo 18F-FDG. Isso poderia significar algum tipo de dissociação entre a perfusão e o metabolismo. Conclusão: Nossos achados sugerem que não há concordância diagnóstica e topográfica perfeita entre a imagem do metabolismo de glicose por PET com 18F-FDG e o padrão de perfusão cerebral usando o marcador PET 11C-PIB em certas estruturas cerebrais em idosos saudáveis, CCLa e pacientes com DA, na quantificação por SPM e na análise visual. Como um biomarcador duplo, a PET 11C-pPIB pode fornecer informações complementares sobre alterações fisiológicas no envelhecimento, e ajudar a elucidar e entender melhor a patologia das doenças relacionadas a memória / Introduction: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer´s Disease (AD). Beta-amyloid plaque deposition can be assessed by 11C-PIB PET while 18FFDG PET is used to assess cerebral glucose metabolism, which can be an indicator for neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of PET-amyloid radiopharmaceuticals can determine regional cerebral blood flow. More studies correlating early-phase 11C-PIB (11C-pPIB) and 18F-FDG are still needed considering that blood flow and cerebral glucose metabolism are usually coupled at rest and during neuronal activations. The aim of this study is to evaluate topographic similarities and differences between cerebral perfusion images obtained with early 11C-PIB PET images and the metabolic images obtained with 18F-FDG PET. Methods: CAPEPesq: Nº1.454.598. Ninety-three subjects were allocated into three groups according to clinical diagnosis: Alzheimer\'s disease (AD, n=27); Mild Cognitive Impairment amnestic (aMCI, n=39); Elderly healthy control (n=27), they underwent T1-weighted MRI and PET/CT imaging. 18F-FDG PET/CT acquisition was performed 30 minutes after tracer injection and 11C-pPIB PET/CT was acquired immediately after the tracer injection and the first 10 minutes of the acquisition was considered in the analysis. PET images were corrected for partial volume effect and the images were spatially normalized using a custom anatomical template of the sample itself, for analysis by Statistical Parametric Mapping (SPM8). Visual and individual analysis were performed by two experient nuclear medicine physicians, blind in relation to the identification of the images, their respective radiopharmaceuticals and clinical diagnosis. They were asked to provide a diagnosis and to indicate their level of confidence on the basis of visual inspection of 18F-FDG and 11C-pPIB images, and also individual assessment of SPM t-maps (voxel-based analysis comparing a single subject of AD group to a cognitively normal control group). Results and Discussion: In the analysis by SPM, the 11C-pPIB showed lower cortical diffuse uptake than 18F-FDG. In the analysis between groups, there is a difference in 11CpPIB and 18F-FDG uptake, what is expected since biodistribution is a particular propriety of each PET tracer. The control group versus the AD group, individuals with AD presented a decreased 11C-pPIB uptake in the temporo-limbic regions: amygdala and hippocampal (L = left) P = 0.006; amygdala and hippocampal (R = right) P = 0.023; parahippocampal gyrus (L) P = 0.008 (R) P = 0.015; and superior temporal (L) P = 0.012 (R) P = 0.015. In the 18F-FDG, there was a decreased uptake in the AD group compared to the control group in the following regions: posterior cingulate cortex (L) P = 0.028; precuneus (L) P= 0.029; medial temporal gyrus (L) P = 0.039; and inferior temporal gyrus (L) P = 0.044. In the comparison of aMCI group versus the control group, individuals with aMCI presented a decreased 11C-pPIB uptake in the region: parahippocampal gyrus (L) P = 0.012. In the visual identification, 100% of 18F-FDG PET images and 99% of 11C-pPIB PET images were correctly recognized. In the visual and individual analysis, it was observed reductions in 11C-pPIB uptake involving medial temporal region in the AD subjects that was not detected by 18F-FDG.This could mean some kind of decoupling between perfusion and metabolism. Conclusion: Our findings suggest that there is no perfect diagnostic and topographical concordance between the imaging of 18F-FDG PET glucose and the cerebral perfusion pattern using the 11C-PIB PET marker in certain brain structures in healthy elderly, aMCI and patients suggestive of AD, quantification by SPM and visual analysis. As a double biomarker, 11C-PIB can provide complementary information on pathological aging of the brain, and it could help elucidate and better understand the pathology of memory-related diseases