According to cognitive reserve theory, challenging and/or stimulating cognitive activities can build a theoretical reserve, which may lead to a delay in the clinical expression of dementia and/or Alzheimer's Disease. These cognitively stimulating activities are thought to build cognitive strategies and neural pathways that are more efficient, enabling the individual to live symptom-free for a longer period of time. One mechanism through which cognitive reserve can be built is by participating in an occupation high in cognitive complexity. When individuals hold an occupation that is high in complexity, they may build their cognitive reserve in such a manner as to reduce their risk for dementia in late life. Using extant data from an existing longitudinal, population-based study, we examined the effect of various subdomains of cognitive complexity of the longest-held job on dementia risk. In cox regression models, individuals holding agricultural occupations and occupations high in complexity of interaction with machinery, equipment, tools and inanimate objects ("Things") had an increased risk for both AD and dementia. Socioeconomic status was found to partially mediate the relationship between high Things complexity and dementia/AD risk, as well as the relationship between agricultural occupations and dementia/AD risk. While there has been some debate regarding whether results reflect a true effect of occupational complexity or simply an effect of education, results from this study indicate that both occupational complexity and education contribute unique effects to dementia/AD risk. Gender, job duration, and APOE genotype were not found to moderate any of the above associations. An understanding of how occupational complexity impacts cognitive reserve and risk for dementia/AD will enable individuals as well as clinicians to implement activities that enhance cognitive reserve and lead to a greater number of years lived symptom-free from dementia/AD.

Background Dementia is a national priority for Scotland, and as such, fast and accurate diagnosis plus responsive and well-evidenced interventions post-diagnosis are key. Accurately estimating an individual’s level of premorbid functioning can be a crucial part of establishing that cognitive decline has taken place, enabling clinicians to be more confident and accurate in their diagnosis. Measures that assess premorbid ability should be able to 1) capture current ability in healthy controls and 2) resist the effects of cognitive decline when used in individuals with dementia. At the post-diagnostic stage, there is a growing evidence base for non-pharmacological, tailored interventions for individuals with dementia. However, the evidence base is limited, particularly so for Cognitive Rehabilitation. Objectives An empirical study was conducted in order to assess whether a newly developed measure that aims to capture lifelong cognitive reserve (the brain’s ability to withstand pathological change), the Cognitive Reserve Index Questionnaire (CRIq), can capture premorbid ability. Three research questions were addressed; 1) does the CRIq capture current ability in healthy controls? 2) is it resistant to cognitive decline when used with a patient group with dementia? and 3) how does the CRIq compare to a traditional measure of premorbid ability, the NART (National Adult Reading Test)? Another focus of development and innovation in dementia research is that of post-diagnostic interventions. A systematic review was therefore conducted in order to evaluate the effectiveness of Cognitive Rehabilitation for mild-moderate dementia (Alzheimer disease or mixed dementia) in relation to cognitive and functional outcomes. Due to the limited number of RCTs in this field precluding a clear understanding of the evidence base, the additional contribution of non-RCTs was also evaluated. Method For the empirical study N=20 healthy older controls and N=13 patients with dementia were recruited. In order to appropriately address the three research questions both groups were assessed using the NART, the CRIq and the MOCA (Montreal Cognitive Assessment). In addition, the control group were assessed on a measure of current ability, the WAIS-IV Perceptual Reasoning Index. For the systematic review of Cognitive Rehabilitation the CDCIG Specialised Register, ALOIS, was searched in order to identify relevant studies. In addition, previous reviews were searched to identify studies excluded on the basis that they were not an RCT. Results Results for the empirical study show both CRIq and NART were strongly correlated to current ability (performance on WAIS-IV PRI) in controls, although both significantly overestimated ability. CRIq performance was not affected by the presence of dementia whereas NART predicted premorbid ability was. CRIq and NART showed a different pattern of results between controls and patients, indicating that CRIq may more resistant to the effects of cognitive decline. Ten studies were identified for the systematic review; five RCT and five non-RCT. Study quality was assessed using a well-validated quality assessment tool, and indicated large variability. Eight of the ten studies reported a positive effect of Cognitive Rehabilitation. However, several studies were of poor quality and included aspects of other approaches in their intervention (e.g. Cognitive Training, Cognitive-Behaviour Therapy). Conclusions The empirical study found that CRIq over-estimated current ability in controls, but was resistant to cognitive decline in patients. The over-estimation of current ability may be accounted for by the CRIq being normed on an Italian population, thus not reflecting UK cultural norms (e.g. for length of schooling). When the NART and the CRIq were directly compared, the two measures were found to be related, but yet produced significantly different estimates of premorbid ability. This suggests that they may capture different facets of premorbid functioning, with the NART being primarily a verbal performance-based measure, and the CRIq capturing aspects of global cognitive functioning. Clinical implications include the potential utility of the CRIq for patients with language impairment. However the study conclusions are limited by a low N, and therefore have restricted generalisability. In the systematic review, the literature was exhaustively searched and evidence was found for the effectiveness of Cognitive Rehabilitation for mild-moderate Alzheimer disease and mixed dementia. Methodological limitations of the included studies are discussed, and clinical implications are identified. Both the empirical study and the systematic review highlight the need for greater research and development of methods by which dementia care is supported; through more effective methods of diagnosis, to a better evidence base for post-diagnostic interventions.

A Doença de Parkinson (DP) é uma das doenças degenerativas do Sistema Nervoso Central que mais acomete indivíduos no mundo. Apesar de a DP ser descrita classicamente como desordem do movimento, sintomas não motores também fazem parte da apresentação da doença, como as alterações cognitivas, que podem estar presentes antes mesmo de os sintomas motores serem percebidos. Os principais domínios cognitivos afetados na DP são as funções executivas (FE). Estas consistem num contingente de funções de ordem superior, que são cruciais para cognição, emoção e comportamento. Muitos estudos abordam a influência das FE no controle da marcha, já que esta não é mais considerada como um ato motor puramente automático. De fato, existem componentes cognitivos na generalização e manutenção de um padrão de marcha consistente e normal, o que justifica os prejuízos neste controle interdependente entre FE e marcha na DP. O objetivo deste estudo foi avaliar a eficiência de um treino original de marcha com demandas motoras e cognitivas desafiadoras, integradas em um contexto funcional em pacientes com DP em estágio inicial. Trata-se de um ensaio clínico cego e randomizado realizado na Associação Brasil Parkinson em São Paulo. Participaram do estudo 25 pacientes com DP nos estágios 1 a 2,5 da escala Hoehn & Yahr. Eles foram distribuídos aleatoriamente nos grupos experimental (GE: 13 sujeitos) e controle (GC: 12 sujeitos). Os dois grupos foram submetidos a 10 sessões de treinamento, com duração de 60 minutos cada uma (divididos em 25 minutos de exercícios de mobilidade global e 35 minutos para os treinos específicos), com frequência de duas vezes por semana, por 5 semanas. O treino experimental consistiu em treino de marcha com demandas motoras desafiadoras e demandas cognitivas constituídas por seis tarefas que exigiam as principais FE envolvidas na realização da marcha, que foram integradas em um contexto funcional. O treino 12 controle consistiu apenas de demandas motoras desafiadoras. As principais medidas foram: (1) Dynamic Gait Index (DGI); (2) Montreal Cognitive Assessment (MoCA); (3) teste de marcha em 30 segundos em dupla-tarefa cognitiva; (4) sessão II da Escala Unificada da Doença de Parkinson (UPDRS). Anova de medidas repetidas seguida de teste de Tukey avaliou a existência de diferenças dentro de cada grupo, em avaliações realizadas antes (AT), depois (DT) e após 60 dias do final do treinamento (RET). Resultados mostraram melhora estatisticamente significativa no DGI, MoCA, teste de marcha em dupla tarefa cognitiva, e sessão II da UPDRS. Entretanto, na medida de seguimento após 60 dias, para várias medidas foram observadas diferentes tendências entre os grupos: o GE apresentou uma tendência à manutenção dos ganhos, ao passo que o GC apresentou uma tendência à remissão dos ganhos. Conclui-se que os pacientes com DP lograram melhoras nos âmbitos motor, cognitivo e funcional por meio de um treinamento baseado na associação de tarefas cognitivas à marcha dentro de um contexto funcional, ganhos estes possivelmente mais estáveis em comparação aos oriundos do treino motor isolado / Parkinson\'s disease (PD) is one of the most frequent degenerative diseases of the central nervous system. Despite being classically described as a motor disorder, non-motor symptoms such as cognitive disorders are also part of the disease, and may be present even before patients become aware of their motor disorders. The main cognitive domains that are affected in PD are executive functions (EF). They consist of a number of higher-order functions, which are crucial for cognition, emotion and behavior. Several studies address influence of EF upon gait control, since gait is no longer considered as a purely automatic motor act. In fact, there are cognitive components in the generalization and maintenance of a normal consistent gait pattern. This helps explain why damages in EF affect gait control in PD, and gait affects EF. The study aimed to assess the effectiveness of an original gait training with challenging motor and cognitive demands, which are integrated in a functional context in patients with early PD. It consists of a blind randomized clinical trial, which was conducted at the Brazil Parkinson\'s Association in Sao Paulo. In the procedure 25 patients, with PD in stages 1 to 2.5 on Hoehn & Yahr scale, were randomly assigned to experimental group (13 subjects) and control group (12 subjects). Training consisted of 10 sessions, 60 minutes each. Sessions were divided into global mobility exercises (25 minutes) and training (35 minutes). Sessions occurred twice a week over five weeks. Experimental training consisted of a gait training with challenging motor demands and cognitive demands. There were six tasks that demanded important EF involved in gait performance, which were integrated into a functional context. Control training consisted only of challenging motor demands. Measures included: (1) Dynamic Gait Index (DGI); (2) Montreal Cognitive Assessment (MoCA); (3) gait test for 30 seconds in dual-cognitive task; (4) session II of the Unified Parkinsons Disease Rating Scale (UPDRS). Repeated measures ANOVA followed by Tukey tests were used to assess the existence of differences 14 within each group, in measures taken before training, after training, and in a follow-up 60 days after training. Both groups showed improvement in DGI, MoCA, gait test in dual-cognitive task, and session II of the UPDRS. However, in the follow-up assessment 60 days after training different trends were observed between the groups: EG showed a tendency to maintain gains, whereas CG showed a tendency to remission of gains. In conclusion, PD patients showed improvements in motor, cognitive and functional areas through a combination of a training based on challenging cognitive tasks on gait integrated in a functional context. Such gains were possibly more stable than those derived from gait training alone

Antalet med en demenssjukdom ökar i världen och siffran drabbade förväntas stiga till 132 miljoner år 2050. Kartläggning av riskfaktorer är en viktig del av det preventiva arbetet. Vissa studier har visat att socioekonomisk status och utbildning har ett samband med risk för att drabbas av demenssjukdom. I denna studie undersöktes relationen mellan utbildning, yrkesbaserad socioekonomisk status och risk för demenssjukdom, samt ifall utfallet ser olika ut för män respektive kvinnor. Ett stickprov med 489 personer från ett longitudinellt forskningsprojekt i Umeå undersöktes varav 70 personer var drabbade av demenssjukdom. Låg yrkesbaserad socioekonomisk status visade sig mer än fördubbla risken att insjukna i en demenssjukdom jämfört med de som hade en hög yrkesbaserad socioekonomisk status. Inget signifikant samband identifierades mellan utbildningslängd och demensinsjuknande, däremot observerades en interaktionseffekt mellan kön och utbildningsnivå där kvinnor med längre utbildning verkade få ett ökat skydd mot att insjukna i demens. Resultaten går till viss del i linje med kognitiv reservteori som bland annat menar att ett högstatusyrke med mer kognitiv stimulans under livet gör individer mer motståndskraftiga mot ett demensinsjuknande. Det är även möjligt att faktorer tidigt i livet, såsom socioekonomisk status under barndomen och kognitiv förmåga, medierar associationen mellan socioekonomisk status och demens. Detta undersöktes dock inte i denna studie men skulle kunna vara av intresse att inkludera i framtida och större longitudinella studier. / The prevalence of dementia in the world is rising and is expected to reach 132 million in the year 2050. Investigating risk factors is an important part of preventive efforts. Some studies have shown that socioeconomic status and education is associated with an increased risk of dementia. This study investigated the association between education, occupational socioeconomic status and dementia. Furthermore, outcomes for men and women were investigated. A sample of 489 people from a longitudinal study in Umeå, Sweden, was examined and 70 people in the sample was afflicted by dementia. Low occupational socioeconomic status was shown to more than double the risk of being afflicted by dementia compared to those with a high occupational socioeconomic status. No significant association could be identified between the length of education and dementia but an interaction between gender and length of education was identified where more years of education had a protective effect for women. The findings are partially consistent with the cognitive reserve theory, which states that having an occupation with higher status and more cognitive stimulation during life will postpone dementia onset. It is also possible that early life circumstances like childhood socioeconomic status and cognitive ability mediates the association between socioeconomic status and dementia which makes this an interesting area of exploration for future research.

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

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

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