There is two different ways to react to a disease like Mild cognitive impairment and Alzheimer’s disease, pathological and clinical. What if there was a way to delay the clinical expression of a disease through pathology? The cognitive reserve has been proven to show a more rapid decline in the individuals that had higher reserve. The purpose of this study was to see if the cognitive reserve actually had an impact on the outcome of Dementia and Alzheimer’s disease. A total of 53 patients with varying degrees of disease pathology and clinical symptoms participated in the study. The results demonstrated that the cognitive reserve makes an impact on the clinical expression, the individuals with high cognitive reserve have a delayed clinical expression comparatively with those with low reserve. Studies of the cognitive reserve may point the way to successful interventions that can help maintain successful aging and slow the onset of dementia.

Hyperbaric Oxygenation Therapy (HBOT) has a successive history for treating very specific groups of physical conditions. Research by Neubauer and colleagues states that HBOT's ability to increase cerebral metabolism in the brain regenerates dormant neural tissue (Neubauer, Gottlieb, & Pevsner 1994). According to this research, the increase of cerebral metabolism levels restores mental capacity from the neurological insult. Despite promise, uncertainty exists as to whether this is a viable treatment option for people suffering from neural damage. The research results for this experiment will examine the effect of HBOT on cerebral metabolism levels in adults and pediatrics with chronic neurological problems. Fifty individuals diagnosed as having a neurological impairment whom met criteria for the study were analyzed from an archival data set. Criterion required chronic impairment, baseline SPECT, followed by HBOT exposures, and a post SPECT scan. Statistical analyses consisted of a Pearson correlation that examined pre-metabolism rates with total change, a Pearson correlation that examined total change and number of treatments, and a one way ANOVA analysis that examined cerebral metabolism change in patients under 18 and over 18. Results indicated change

Um dos desafios fundamentais para a pesquisa gerontológica é como manter e promover o funcionamento cognitivo preservado na velhice. O presente estudo está dividido em dois artigos. O primeiro artigo tem como objetivo verificar diferentes perfis de ganho cognitivo em idosos para a reserva cognitiva. Apresenta dados de uma scoping review sobre reserva cognitiva e os diferentes efeitos das intervenções realizadas. Foi realizado um levantamento de estudos publicados entre janeiro de 2008 até agosto de 2018, nas bases de dados PubMed, Medline, Web of Science, Science Direct, Lilacs, SciELO, PsycInfo, PsycNet e AgeLine usando as seguintes palavras-chave \"reserva cognitiva\" e {envelhecimento ou \"velhice\" ou \"pessoas velhas\" ou \"adultos idosos\"} e, os termos em inglês \"cognitive reserve\" AND {aging OR \"old age\" OR \"old people\" OR \"old adults\"}. Foram identificados 2295 estudos, 51 foram elegíveis para a scoping review. Dentro os 51 estudos selecionados, foram encontrados 9 perfis diferentes para manutenção cognitiva, sendo que 5 estudos não especificaram o perfil. Os perfis encontrados representam relevância para a teoria de reserva cognitiva e fornece esclarecimentos de como fatores individuais e de vida diária podem fazer o cérebro mais resiliente no envelhecimento e na velhice, porém, como os fatores individuais contribuem para o desenvolvimento da RC e manutenção da cognição, é uma questão ainda não explicada pela literatura. O segundo artigo dedicado à exposição do delineamento de uma pesquisa empírica, avalia a associação entre cognição e atividades avançadas de vida diária em uma amostra de idosos brasileiros residentes na comunidade, como forma de contribuir para o entendimento destes perfis para as melhoras em suas capacidades cognitivas. Tratou-se de uma análise transversal de 271 idosos, com 80 anos ou mais, participantes de uma fase de acompanhamento (2016-2017) de um estudo de base comunitária denominado FIBRA. A primeira onda de coleta de dados ocorreu entre 2008 e 2009. No estudo de acompanhamento, os domicílios dos participantes de dois locais, Campinas e Ermelino Matarazzo, foram revisitados e novos dados foram coletados daqueles que aceitaram participar dessa fase. Os participantes completaram um bloco de medidas que incluiu informações sociodemográficas, testes cognitivos Mini-Exame do Estado Mental (MEEM) e Mini Exame Cognitivo de Addenbrooke (M-ACE). Os participantes obtiveram um bom desempenho na avaliação global da cognição pelo MEEM, com média de 24,9 (±2,89). Observando-se a média (24,91 ± 2,89) do MEEM, nota-se que os participantes apresentam bom desempenho cognitivo, de acordo com a avaliação global da cognição. Os resultados apontam ainda que estudar 9 anos ou mais, ter mais de 50 livros na infância, participar de eventos culturais, dirigir, realizar trabalho voluntário, participar de diretorias, ler, acessar o e-mail e a internet foram significativamente associadas ao bom desempenho cognitivo. Conclui-se que o MEEM se associou com participação em eventos culturais, dirigir, realizar trabalho voluntário, participar de diretorias e ler após ajuste com variáveis gênero, faixa etária e escolaridade / One of the challenges for gerontological research front of cognitive reserve is how to maintain and promote cognitive functioning preserved in old age. Currently, studies on cognition, aging and old age have progressed significantly. The first article with the objective of verifying different profiles of cognitive gain in the elderly for the cognitive reserve presents data from a scoping review in order to evaluate the cognitive reserve and the different effects of the interventions performed. A study was carried out between January 2008 and August 2018 in the PubMed, Medline, Web of Science, Science Direct, Lilacs, SciELO, PsycInfo, PsycNet and AgeLine databases using the following keywords \"cognitive reserve\" and {aging or \"old age\" or \"old people\" or \"elderly adults\"} and the terms \"cognitive reserve\" AND {aging OR \"old age\" OR \"old people\" OR \"old adults\"}. We identified 2295 studies, 51 were eligible for scoping review. Within the 51 selected studies, 9 different profiles were found for cognitive maintenance, and 5 studies did not specify the profile. The profiles found represent relevance to the theory of cognitive reserve and provides insights into how individual and daily life factors can make the brain more resilient in aging and old age, but how individual factors contribute to the development of CR and maintenance of cognition, is an issue not yet explained in the literature. The second article on the design of an empirical research evaluates the association between cognition and advanced activities of daily living in a sample of Brazilian elderly people living in the community as a way to contribute to the understanding of these profiles for improvements in their cognitive abilities. This was a cross-sectional analysis of 271 elderly people, aged 80 years and over, who participated in a follow-up phase (2016-2017) of a community-based study called FIBRA. The first phase of data collection occurred between 2008 and 2009. In the follow-up study, the households of participants from two sites, Campinas and Ermelino Matarazzo, were revisited and new data were collected from those who agreed to participate in this phase. Participants completed a block of measures that included sociodemographic information, cognitive tests Mini-Mental State Examination (MMSE) and Addenbrooke\'s Mini Cognitive Examination (M-ACE). Participants performed well in the overall evaluation of cognition by the MMSE, with an average of 24.9 (± 2.89). Observing the mean (24.91 ± 2.89) of the MMSE, it is observed that the participants present good cognitive performance, according to the global assessment of cognition. The results also point out that studying 9 years or more, having more than 50 books in childhood, participating in cultural events, directing, volunteering, attending boardrooms, reading, accessing e-mail and the Internet were significantly associated with good performance cognitive. It was concluded that the MMSE was associated with participation in cultural events, direct, volunteer work, participate in boards and read after adjustment with variables gender, age group and schooling

Background: Good social connections have been identified as a factor that may be associated with healthy cognitive function in later life. In line with cognitive reserve theory, good social connections may provide mental stimulation through complex interaction with others and hence build cognitive reserve and maintain healthy cognitive function. However, there is considerable inconsistency in findings reported by studies that examine this association. Inconsistency in findings may be attributed to the heterogeneity of concepts potentially associated with social connections and to the variation in approaches to measuring and defining these concepts. Aims: To assess the association between aspects of social connections and cognitive function in later life. This thesis introduces a novel element by considering the moderating role of cognitive reserve in this association. Method: A scoping review was conducted to establish which concepts are used within the literature to describe social connections and how these are measured and defined. Next, a systematic review and meta-analysis was conducted to identify evidence regarding the association between social isolation and cognitive function in published studies. Empirical work was conducted using cross-sectional and longitudinal data from the Cognitive Function and Ageing Study-Wales (CFAS-Wales) to determine the associations between social isolation, cognitive reserve, and cognitive function in healthy older people. Extending this approach further, these associations were examined in two groups potentially at risk of social isolation: older people with depression or anxiety and older people living alone. Finally, empirical work was completed using the Platform for Research Online to investigate Genetics and Cognition in Ageing (PROTECT) to assess how satisfaction with social contact may be associated with cognitive function compared to a structural measure of isolation. Results: A lack of social connections was associated with poor cognitive function in later life. For people with depression or anxiety, these associations may be better explained by mood-related symptoms than social connections. People who live alone in later life were at no greater risk of poor cognitive function compared to those living with others. Satisfaction with social contact was associated with poor cognitive function but a structural measure of social isolation was not. Conclusions: Social connections play an important role in building cognitive reserve and protecting people against poor cognitive function in later life. People who are vulnerable to social isolation have different needs to those who are less vulnerable. Satisfaction with social contact is often neglected in measures that assess structural aspects of social connections but may be a better predictor of cognitive function.

A small subset of individuals that have experienced mild traumatic brain injury (mTBI) may experience persistent cognitive deficits more than a year following the head injury. Neuroimaging studies reveal structural and functional changes in frontal areas of the brain, exacerbated when loss of consciousness is experienced, and indicate that these changes may be progressive in nature for some people. Social support and social participation have, however, been suggested to confer cognitive reserve - neurocognitive protection against cognitive decline. Analyses were run on Canadian Longitudinal Study on Aging (CLSA) neuropsychological data, consisting of individuals who experienced mTBI with loss of consciousness (n = 536 for less than 1 minute, and n = 435 for unconsciousness between 1 and 20 minutes) more than a year prior, and 13,163 no-head injury comparisons. These same individuals were re-assessed three years later. The results presented in this thesis suggest that at a year or more after a single mTBI with loss of consciousness, a small subset of individuals are more likely to be impaired on prospective memory and other executive functioning tasks, relative to comparisons. In addition, when examined at three-year follow-up, those who experienced mTBI with longer duration of unconsciousness were more likely to exhibit cognitive decline relative to those who experienced less unconsciousness or comparisons. Moreover, greater social participation over the past year, and more perceived social support were predictive of lessened cognitive deterioration in those individuals.

This research involves an examination of the relationship between education and age on a wide array of neuropsychological test measures among patients diagnosed with Alzheimer's and vascular dementia. The purpose of this study was to investigate the role of education as an attenuating factor to neurocognitive decline in dementia. Although numerous studies have been published regarding the relationship between educational attainment and AD, few have included other subtypes of dementia in their investigation. To further expand the generalizability of previous findings, the sample in this study included both AD and VaD. While previous research has demonstrated a relationship between education and age-related neurocognitive decline in AD, most studies have utilized the MMSE or brief screening instrument to assess cognitive functioning. The present research included VaD and examined a variety of cognitive domains such as measures of global functioning, verbal intelligence, verbal memory, visual memory, attention/concentration, language, visuospatial skills, speed-of-processing, and abstract reasoning/executive functioning. Two standard multiple regression analyses were conducted, the first including age and education as the independent variables to assess the effects on one over and above that of the other. The second analysis included age, education, and their interaction term in order to determine if education attenuates age-related neurocognitive decline in the diagnostic groups. Raw neuropsychological test measure scores were included in all analyses as dependent measures. Results revealed that age minimally predicted performance in both groups, whereas education better predicted neurocognitive test performance in the AD group than in the VaD group. Furthermore, findings suggest that among individuals with AD, the rate of neurocognitive impairment in encoding verbal information and visuoconstructional ability is buffered by higher levels of education attainment. None of the interaction terms were significant for the VaD group. The current findings question the extent and generalizability of the presumed protective effects of higher education on age-related neurocognitive decline.

Le vieillissement est un phénomène biologique complexe et inévitable associé à un déclin progressif des fonctions cognitives, sensorielles et motrices qui affecte la qualité de vie et la santé des sujets âgés. Le vieillissement normal s'accompagne de changements structuraux et fonctionnels, conduisant au déclin cognitif. Parmi ces changements, les altérations du système noradrénergique semblent contribuer de façon significative aux déficits cognitifs. Inversement, le maintien de l'intégrité du Locus Coeruleus semble participer à la préservation des performances. Par ailleurs, une stratégie pour promouvoir le bien vieillir propose de booster la réserve cognitive associée à un haut niveau de stimulation cérébrale et à des modulations de l'activation et de la connectivité cérébrales chez l'humain. Chez les rongeurs, l'enrichissement environnemental promouvant les stimulations sensorielles, l'activité motrice et les interactions sociales, mime les conditions de mise en place de la réserve cognitive chez l'homme et a largement montré ses effets bénéfiques sur la cognition. Les objectifs de cette thèse sont premièrement, d'étudier le rôle de la NA dans le maintien de la plasticité structurale et des capacités de discrimination olfactive chez la souris âgée, puis dans un second temps de tester l'enrichissement olfactif comme modèle de construction de la réserve cognitive. Dans une première étude, nous avons utilisé le modèle d'apprentissage perceptif olfactif pour étudier la contribution de la Noradrénaline au maintien de la plasticité structurale et des performances cognitives au cours du vieillissement chez la souris. Cet apprentissage consiste en une amélioration de la discrimination entre deux odorants proches sur le plan perceptif après une exposition répétée à ces odorants. Nos résultats suggèrent que la libération de Noradrénaline dans le bulbe olfactif via une stimulation optogénétique des fibres issues du Locus Coeruleus maintient les capacités de discrimination au cours du vieillissement. Nos données révèlent aussi une forme de plasticité du réseau noradrénergique dans le bulbe olfactif âgé. Ces résultats soutiennent l'hypothèse d'une contribution importante de la Noradrénaline au bien vieillir cérébral. Dans une deuxième étude, nous avons utilisé une stratégie basée sur un enrichissement olfactif, manipulation capable de mobiliser la Noradrénaline, proposé tout au long de la vie de l'animal, dans le but de permettre le développement d'une réserve cognitive. Nos résultats montrent qu'un tel enrichissement améliore les capacités de discrimination olfactive même à un âge avancé. De façon intéressante, les performances non olfactives de mémoire spatiale et de flexibilité sont aussi améliorées. Ces résultats indiquent que les effets bénéfiques de l'enrichissement s'étendent au-delà de la sphère olfactive et incluent des bénéfices sur différentes performances cognitives sensibles à l'âge. Nous proposons donc l'enrichissement olfactif comme un modèle de la construction d'une réserve cognitive qui nous permettra par la suite d'identifier les bases cellulaires du bien vieillir et de tester la contribution de la Noradrénaline dans la construction de la réserve cognitive / Aging is an inevitable and complex biological phenomenon associated with a progressive decline of sensory, motor and cognitive functions with time, affecting life quality and health. Normal brain aging is accompanied by functional and structural changes, leading to cognitive decline. Among these changes, age-related alterations of the noradrenergic system seem to contribute significantly to cognitive deficits. Conversely, the integrity of the Locus Coeruleus seems to allow healthy cognitive aging. A potentially powerful tool to achieve successful brain aging is to boost the cognitive reserve, associated with higher level of brain stimulation and modulations in brain activation and connectivity in humans. In rodents, environmental enrichment, increasing sensory stimulations, motor activity and social interactions, mimics the conditions leading to constitution of the cognitive reserve in humans and has largely proven cognitive benefits.The goals of this thesis are, in the first place, to study the role of Noradrenaline in the maintenance of structural plasticity and olfactory discrimination abilities in aged mice, then secondly, to test the olfactory enrichment as a model of the cognitive reserve build-up.In the first study, we used the olfactory perceptual learning paradigm to investigate the contribution of Noradrenaline to the maintenance of structural plasticity and cognitive abilities during aging in mice. This learning consists in an improvement of the discrimination between perceptually close odorants after repeated exposure to these odorants. Our results suggest that the local release of Noradrenaline in the olfactory bulb, by optogenetic stimulation of Locus Coeruleus fibers allows the maintenance of discrimination abilities during aging. Our data also reveal a form of structural plasticity of the noradrenergic innervation in the aged olfactory bulb. The overall work supports a contribution of Noradrenaline to healthy brain aging.In a second study, we used a strategy based on repeated olfactory enrichment during the whole life of the animal in order to enable the cognitive reserve buildup. Such enrichment maintained olfactory discrimination performances at late ages. Interestingly, mice’s performances in spatial memory and cognitive flexibility improved too. This result indicates that the benefits of an odor-based enrichment extend beyond the olfactory sphere and include broader cognitive benefits on age-sensitive functions. We thus propose lifelong olfactory enrichment as model of the cognitive reserve build-up to further identify its cellular basis and test the contribution of Noradrenaline to cognitive reserve build-up and healthy brain aging

Individuals who speak more than one language have been found to enjoy a number of benefits not directly associated with the use of the languages themselves. One of these benefits is that bilingual individuals appear to develop symptoms of dementia 4-5 years later than comparable individuals who speak just one language. Studies on this topic, however, do not consistently account for factors including if the individual learned their second language as a child or later in life, or their language proficiency. In an attempt to more carefully examine these variables, this study looks at structural and resting-state functional MRI scans of the default mode network, English and Spanish (where applicable) proficiency, language background, and demographics of young healthy adults who fall into one of three groups: early bilinguals, late bilinguals, and monolinguals. Of the three groups, late bilinguals were found to have a small but statistically significantly higher level of connectivity compared with early bilinguals in the region of the medial prefrontal cortex; patterns found examining number of languages and language proficiency in relation to functional connectivity and research group also supported this finding. These results indicate studying a language after adolescence could provide neuroprotective benefits of a nature that could potentially help delay symptoms of dementia. Age, gender, ethnicity, level of education, English language proficiency, and Spanish language use did not result in statistically significant findings, the latter of which challenges using frequency of language use to define bilingualism.

Alzheimer’s disease is an insidious neurodegenerative disease that affects millions of people worldwide. Currently, there are no determinants that can accurately predict the onset cognitive decline in AD. This thesis investigates and defines changes in the lipidome that are linked to symptomatic onset and cognitive impairment in mouse models of AD. Using a targeted lipidomic approach employing high performance liquid chromatography electrospray ionization tandom mass spectrometry, direct biochemical assessments, and behavioural evaluation, I was able to (a) profile and quantify cortical and hippocampal glycerophosphocholine and glycerophosphoethanolamine metabolites and signaling molecules in the APPSwe/PS1dE9 and the N5 TgCRND8 murine models of AD and (b) associate changes in lipid metabolism with learning and memory impairment. I demonstrate that glycerophosphocholine metabolism in the cortex but not the hippocampus is altered at symptomatic onset in both mouse models. These same metabolic changes were seen in younger animals exposed to chronic intermittent hypoxia, an environmental risk factor that accelerates their phenoconversion. In fully impaired transgenic mice, I defined metabolic changes associated with disease progression. To further assess the impact of sex, another risk factor of Alzheimer’s disease cognitive decline, I characterized an AD model of sex-specific cognitive resistance. I demonstrated that transgenic males but not females exhibit behavioural indices of cognitive reserve when tested in the Morris Water Maze. Using this mouse line, I then investigated how measures of learning and memory associated with glycerophosphocholine and glycerophosphoethanolamine metabolism. I identified increases in critical glycerophosphoethanolamine metabolites linked to spatial learning and memory impairment in the cortex of N5 TgCNRD8 mice and demonstrated that these changes could be predicted by profiling the plasma glycerophosphoethanolamine lipidome. Taken together, this thesis links glycerophospholipid metabolism to the onset and progression of learning and memory impairment in experimental models of AD and provides the first evidence that changes in cortical lipid metabolism can be predicted by changes in the plasma lipidome.

According to the theory of cognitive reserve, cognitively enriching aspects of life experience (e.g., education, occupation, and leisure activity) foster the development of more efficient neural networks and cognitive strategies, enabling individuals to cope more effectively with the pathology of dementia. Using extant data from a population-based study, we examined: (1) the effect of reserve accrued through middle life on course of neuropsychological decline; and (2) the role of ongoing engagement in mentally stimulating leisure activities in rate of general cognitive and functional deterioration. In linear mixed models, level of occupational attainment did not affect rate of cognitive or functional decline, although women were found to undergo more rapid deterioration in cognitive ability. Occupational skill area was associated with trajectory of decline in several neuropsychological domains. Specifically, vocations emphasizing practical, hands-on skills were associated with slower deterioration in auditory-verbal and visual memory, as well as visuospatial and constructional abilities. Teaching and helping professions, in contrast, were associated with more rapid decline in memory and executive functioning. Increased engagement in cognitive leisure activities through late life was associated with slower deterioration in general cognitive ability in mild dementia, but its effects were no longer evident in more severe AD. An understanding of how rate of decline intersects with patients' past histories and efforts to maintain and enhance cognitive capacity will enable clinicians to target areas for cognitive training and rehabilitative therapy.