The concept of resilience, which indicates people's capability of using resources in difficult circumstances in order to reduce or prevent negative effects and achieve positive outcomes, has given a new perspective to the scientific literature on the experience of late-life memory loss and the experience of caring for persons with memory loss. The current research was guided by incorporation of resilience into the stress process model for assessing personal and caregiver burden associated with mild and more severe memory loss. I conducted two studies to investigate the association of protective factors with the well-being of people with dementia or mild cognitive impairment and their caregivers. The first study focused on the well-being of older persons with dementia (PwDs). I employed data from a large national sample of older adults to examine how the perceived social cohesion of neighborhoods affects quality of life among people with and without cognitive impairment in conjunction with their engagement in valued leisure activities. Findings revealed that, regardless of cognitive health status, all participants who perceived high neighborhood social cohesion reported better quality of life along with more participation in valued activities. However, PwDs reported significantly lower perceived neighborhood social cohesion, less involvement in valued activities, and poorer quality of life than persons without cognitive impairment. The second study focused on the well-being of caregivers for older persons with mild cognitive impairment (PwMCIs). I used dyadic data from families dealing with mild cognitive impairment to examine how well-being of caregivers for PwMCIs differed according to whether PwMCI-caregiver dyads had similar or different perceptions of the PwMCIs' cognitive impairment severity. Caregivers reported lower caregiving burden when they and PwMCIs had a similar cognitive impairment representation, or when caregivers rated the PwMCIs’ cognitive functioning more positively than the PwMCIs rated themselves. Also, PwMCIs’ and caregivers' perceptions, and their concordance or discrepancy in those perceptions, varied across the multiple domains related to MCI symptoms. These findings demonstrate that care dyads' perception of MCI-related deficits is not a unitary construct, and that the context of PwMCIs’ and caregivers’ dyadic illness appraisals is significantly associated with the caregivers' well-being. Taken together, the results of these two studies illustrate the value of considering resilience processes in people with cognitive impairment and their caregivers. Examining dimensions of resilience, in association with assessment of the intersecting effects of personal, interpersonal, and environmental factors, provides additional information about the effects of cognitive impairment on older adults’ well-being and the effects of assisting someone with cognitive impairment on caregiver well-being. / Ph. D. / Resilience indicates people's ability to successfully adapt to or bounce back from life adversity by using personal, social, and environmental resources. Resilience helps explain what makes some people with dementia and their caregivers tolerant of changes in memory functioning and able to adapt to difficulties associated with dementia. I conducted two studies to investigate the role of protective resources in buffering negative effects of memory loss on people with dementia and their caregivers. The first study compared people with and without dementia to find out how their sense of belonging to the community and their participation in valued leisure activities influenced their quality of life. Regardless of whether they had memory loss or not, all the people with a stronger sense of belonging in the community participated in more leisure and valued activities and, in turn, had better quality of life. However, compared to cognitively healthy people, those with dementia had lower sense of belonging, less participation in leisure activities, and poorer quality of life. These findings indicate that people with dementia may feel excluded from their community and experience barriers to participation in valued activities. Nevertheless, feeling that one belongs in the neighborhood and participating in valued leisure activities is important for well-being of older adults both with and without cognitive impairment. The second study examined how the well-being of caregivers for persons with mild cognitive impairment (MCI) differed according to whether caregivers and their care recipients had similar or different views on the care recipients’ memory problems. When they both had similar views or the caregivers had a more positive view than their care recipients did, the caregivers reported higher well-being. This finding suggests that some caregivers for people with MCI understand how the person with MCI views their own memory loss, and others either are not aware of all the memory loss symptoms or choose to ignore some of them. In either case, these caregivers feel less burdened than those who think their loved one’s symptoms are worse than the person with memory loss believes. Support for these caregivers is needed to help them cope better with the memory loss in their loved one. The results from these two studies provided valuable evidence about resilience in older adults facing memory loss and their caregivers. Being resilient can help people with dementia and their caregivers manage or overcome the difficulties associated with dementia.

Although not all persons with mild cognitive impairment (MCI) go on to develop Alzheimer's disease (AD), MCI is recognized as an early stage of AD. The effects of AD are devastating to all concerned. Research has identified that recognition of AD in its earliest stages and institution of known treatment modalities can forestall the ultimate outcome. Identification of the first subtle signs of MCI can assist in the recognition of this prodromal phase, and allow for institution of therapy while still in the initial stages. Unfortunately, the development of MCI is insidious in nature, thus making it difficult to detect. The purpose of this study was to identify areas of functional decline that occur in MCI in an effort to improve its early identification. A mixed-methods design that combined qualitative and quantitative methods was used. Fifty-three participants with memory complaints were interviewed using a semi structured interview technique with open-ended questions, the Montreal Cognitive Assessment (MoCA), the Geriatric Depression Scale (GDS) and a list of eighty-five items previously identified as indicative of functional decline. Twenty-nine persons were divided into two groups: 1) those identified as probable MCI (consensus diagnosis) (n=15) and possible MCI (based on screening examination) (n=14) and 2) those identified as Normal (no cognitive impairment) (n=10), and their subjective functional deficits compared. The findings suggest that there were certain areas of functional decline more commonly experienced by persons in the MCI group than by unimpaired. These include difficulty recalling details of information and forgetting conversations. There were also other changes identified, such as adaptations on the part of persons with MCI (an increased dependence on memory aids, for example, lists and calendars) and a dec rease in social activities leading to an increase in social isolation. Additionally identified were functional activities that appear to remain intact in persons with early MCI. This study highlights the subtlety with which MCI assaults the functional abilities of individuals, thus making its early identification problematic. The results of this study will contribute by providing information that will help professionals who are assessing persons experiencing memory issues for the possible presence of MCI. Additionally, it is hoped that these findings will assist in the development of a measurement tool designed to assess for possible MCI. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Frontal lobe atrophy (FLA) is associated with late-life depression and cognitive impairment, although the pathogenesis of FLA in stroke is unclear. In an aim to ascertain whether FLA is affected by WMLs, we analyzed the MRIs of 471 Chinese ischemic stroke patients. Lobar atrophy was defined by a widely-used visual rating scale. WML severity was rated using the Fazekas scale. There was no correlation between PVH and DWMH and temporal and parietal atrophy. The results of this study suggest that FLA in ischemic stroke may be associated with SVD. / Poststroke depression (PSD) is the most common form of poststroke psychiatric morbidity. Small subcortical infarcts (SSIs) can result from small vessel disease (SVD) and large artery disease (LAD). No study has yet explored PSD in different etiological types of SSIs. To address this gap, 127 patients with SSIs resulting from LAD or SVD were examined. PSD was evaluated with the Geriatric Depression Scale (GDS) three months after stroke. The LAD group had a significantly higher frequency of PSD, and LAD was found to be a significant independent risk factor for PSD. This study suggests that cerebral blood perfusion may play an important role in PSD. / Post-stroke emotional lability (PSEL) is a distressing and embarrassing complaint among stroke survivors. Lesions located in various cortical and subcortical areas are thought to be involved in the pathophysiology of PSEL.The clinical significance of microbleeds (MBs) in the development of psychiatric conditions following stroke is unknown. We carried out a study to examine the association between PSEL and MBs in 519 Chinese patients with acute ischemic stroke admitted consecutively. PSEL was evaluated three months after the index stroke, and the number and location of MBs were evaluated with MRI. According to Kim's criteria, 74 (14.3%) of the patients had PSEL. Our results suggest that MBs in the thalamus may play a role in the development of PSEL. The importance of MBs in PSEL and other psychiatric conditions in stroke survivors warrants further investigation. / The first study reported in this thesis involved 328 Chinese ischemic stroke patients who were administered a series of neuropsychological tests covering seven domains three months after stroke. Two hundred and fifty-six of these patients were followed-up for one year. Volumetry of the infarcts, WMLs, and hippocampus atrophy on magnetic resonance imaging (MRI) was conducted. The prevalence of cognitive impairment was 54.9% at baseline and 52.4% at the one-year follow-up, although most of the patients (85.5%) remained cognitively stable. The evolution of cognitive impairment no dementia (CIND) at the one-year follow-up was bidirectional, with 11.2% progressing to dementia and 21.0% reverting to cognitive intact. WMLs volume rather than hippocampal volume was a significant predictor of cognitive impairment, cognitive decline, and delayed dementia. WMLs also had an independent effect on executive function, attention, visual memory, visuoconstruction, and visuomotor speed. / This thesis investigates the clinical and imaging characterization of cognitive impairment and psychiatric morbidity in Chinese stroke patients. The conclusions of the studies reported herein can be summarized as follows. (1) The prevalence of cognitive impairment is high among Chinese poststroke patients, but most remain cognitively stable at one year after stroke; WMLs rather than hippocampal atrophy predict cognitive impairment, longitudinal cognitive decline, and delayed dementia; (2) DLPFC atrophy is correlated with poor verbal fluency in elderly women with stroke, but not in their male counterparts; (3) LAD may be associated with PSD in patients with small subcortical infarcts; (4) MBs in the thalamus are associated with PSEL; (5) frontal lobe infarction and diabetes may be risk factors of insomnia symptoms in stroke patients; and (6) FLA in ischemic stroke may be associated with SVD. (Abstract shortened by UMI.) / Chen, Yangkun. / Adviser: Wai Kwong Tang. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 217-238). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Ce travail de thèse s’articule autour de trois études complémentaires. La première aborde la validation française d’un test rapide d’évaluation des fonctions supérieures: le Barrow Neurological Institute Screen for higher cerebral functions (B.N.I.S). Cette étude a permis de rendre disponible en langue française un outil rapide qui évalue les fonctions cognitives classiques mais aussi les capacités émotionnelles et sociocognitives, fonctions généralement non intégrées dans ce type de test. La seconde étude, menée auprès de participants présentant un Mild Cognitive Impairment (M.C.I), a ensuite permis de mettre en évidence la nécessité de prendre en compte l’évaluation émotionnelle. Les participants M.C.I présentent un profil spécifique au B.N.I.S., notamment aux subtests d’affectivité, d’orientation, de mémoire et d’auto-évaluation de la performance mnésique. Enfin, la troisième étude analyse les performances de reconnaissance faciale des émotions et de raisonnement social au cours du vieillissement normal, le Mild Cognitive Impairment et la démence de type Alzheimer (DTA) au stade débutant. Nous observons un déclin des capacités de reconnaissance faciale des émotions et de raisonnement social au cours du vieillissement normal qui s’accentue significativement au cours de la DTA. Un profil spécifique est retrouvé pour le M.C.I avec un déclin en raisonnement social mais des capacités de reconnaissance faciale émotionnelle comparables aux sujets âgés du groupe contrôle. L’évaluation des capacités émotionnelles devrait être davantage intégrée aux bilans neuropsychologiques afin de mieux orienter les modalités de prise en charge de la population vieillissante. / This research presents three complementary studies: (1) the french validation of the Barrow Neurological Institute Screen for higher cerebral functions (B.N.I.S), developed by G. Prigatano in 1991. We have assessed 167 subjects from 15 to 84 years within a french population. The goal is :1) to promote a new short screening instrument dedicated to cognitive and emotional functions, usually emotional functions are not integrated in neuropsychological assessments ; (2) to apply the B.N.I.S to Mild Cognitive Impairment (M.C.I) subjects (N=39) in order to highlighted the importance of the emotional assessment in this type of population and found a specific profile at the substests named: affectivity, orientation, memory and self-assessment of the mnesic performance ; (3) to analyze, with more precision, the performance of emotional facial recognition and social reasoning during normal ageing (N=54), M.C.I (N=25) and Alzheimer disease (AD) at the early stage (N=17). A decline of sociocognitive capacities is observed during the ageing and seems to become more important during the course of M.C.I and the AD. A specific profile was found for each group. The assessment of emotional capacities seems relevant and should be more integrated into the neuropsychological assessments, in order to improve diagnosis and to propose the best modalities of care for the ageing population.

Mexican Americans face a significant health disparity related to the development of Mild Cognitive Impairment (MCI) when compared to other ethnic groups. Recent work has documented the utility of utilizing blood-based biomarkers in the detection of amnestic MCI among this population. Efforts to enhance the utility of biomarkers in detecting disease through the inclusion of select neuropsychological measures, an approach termed Molecular Neuropsychology, has shown promise. The present study sought to utilize the molecular neuropsychology approach and examine biobanked serum samples as well as neuropsychological assessments from the Health and Aging Brain among Latino Elders (HABLE) study. Random Forest analyses were conducted to determine the proteomic profile of MCI. Then separate linear regression analyses were conducted to determine the variance accounted for by the biomarkers within the select neuropsychological measures. Trail Making Test Part B was identified as having the least amount of variance and was combined with top five biomarkers within the MCI proteomic profile to create a biomarker-cognitive profile for detecting disease presence. This same method was applied to the amnestic and non-amnestic forms of MCI. The overall biomarker-cognitive profile was shown to be 90% accurate in the detection of MCI, with no significant increase when demographic variables were included into the model. Among amnestic MCI cases, the detection accuracy of the biomarker-cognitive profile was 92% and increased to 94% upon inclusion of demographic variables.

Introdução: Com o envelhecimento da população mundial projeta-se o crescimento das taxas de doenças potencialmente relacionadas à idade como as demências, especialmente a doença de Alzheimer (DA). Os sujeitos com Comprometimento Cognitivo Leve (CCL) são considerados uma população de risco para desenvolver demência, no entanto, as taxas de incidência de CCL e conversão para demência apresentam considerável variabilidade em parte atribuída a características da amostra e aos diferentes critérios utilizados. Objetivos: Determinar a incidência de demência e Comprometimento Cognitivo Leve em uma coorte de idosos saudáveis de base comunitária; determinar as variáveis demográficas, clínicas e sociais associadas ao desenvolvimento de prejuízo cognitivo, e avaliar o risco de progressão dos indivíduos com Comprometimento Cognitivo Leve para demência comparada com sujeitos cognitivamente normais. Métodos: Os dados foram derivados de uma coorte de idosos residentes na comunidade (N = 345), inicialmente saudáveis e independentes (Estudo PALA - Porto Alegre Longitudinal Aging - study). O seguimento inicial com duração máxima de oito anos teve o objetivo de avaliar a incidência de DA e CCL. Para avaliar a progressão de CCL para DA partimos de 10 anos de seguimento, incluindo os oito anos da primeira análise e consideramos um máximo de 70 meses (média de 45 meses) para avaliar a ocorrência dos novos desfechos. Os participantes que preencheram os critérios de inclusão do estudo e consentiram em participar foram avaliados com uma detalhada entrevista clínica composta de variáveis demográficas, clínicas e sociais. Os sintomas psiquiátricos foram avaliados pela escala SRQ - Self Report Questionnaire, escala MADRS - Montgomery-Asberg Depression Rating Scale e aplicados os critérios para depressão maior do Manual de Diagnóstico e Estatístico de Transtornos Mentais (4ª Edição; DSM-IV). O Mini Exame do Estado Mental (MEEM) e a Escala Clínica de Demência (CDR – Clinical Dementia Rating) foram aplicados para avaliação cognitiva. Adicionalmente a independência para as atividades da vida diária foram acessadas pela escala ADL - Activities of Daily Living. Para diagnóstico dos casos incidentes de doença de Alzheimer foi utilizado os critérios diagnósticos do DSM-IV e do NINCDS/ADRDA, associado à descrição dos critérios de Kawas para DA consistente. Para diagnóstico de Comprometimento Cognitivo Leve, o critério da Clínica Mayo foi aplicado para a primeira análise, e o critério para CCL do tipo Alzheimer (ou DA prodrômica) foi utilizado para a segunda análise tendo em vista a incorporação de dados disponíveis e a evolução dos critérios. As trajetórias possíveis do CCL foram classificadas em três categorias: conversão, estabilização e reconversão. Os sujeitos considerados para a primeira análise - casos incidentes de CCL e DA foram os participantes que apresentavam pelo menos uma visita de seguimento no período de oito anos a partir da linha de base (N = 245) e as análises estatísticas foram baseadas no diagnóstico estabelecido na última visita de seguimento. Para os falecidos durante o período, dados retrospectivos foram obtidos através de uma entrevista telefônica com um informante confiável. Os dados clínicos e demográficos de linha de base foram utilizados para cálculo dos fatores preditivos dos desfechos do estudo. Para a segunda análise – risco de conversão de CCL para DA – trajetórias do CCL, a amostra foi composta dos 21 indivíduos que desenvolveram CCL e 220 indivíduos cognitivamente normais (N = 241). Resultados: Os resultados da primeira análise mostraram taxa de incidência de CCL de 13,2 por 1.000 pessoas-ano e incidência de DA de 14,8 por 1.000 pessoas-ano. O desenvolvimento de prejuízo cognitivo foi associado com educação (razão de chance [RC] = 0,86) e o escore do MEEM de base (RC = 0,81). Os resultados da segunda análise mostraram que dos 21 sujeitos com CCL, 38% desenvolveram demência, 24% permaneceram estáveis e 38% melhoraram. A taxa de conversão anual para DA foi de 8,5%, CCL foi associado significativamente a maior risco de conversão para DA (HR = 49,83; p = 0,004), mesmo ajustado para idade, escolaridade, sexo e escore no MEEM. Conclusão: A incidência de DA nessa amostra foi maior do que a descrita em estudo prévio realizado no Brasil, mas está dentro da variabilidade observada internacionalmente. Escores mais baixos no Mini Exame do Estado Mental na linha de base, mesmo que dentro da normalidade, e níveis mais baixos de educação foram preditores da ocorrência de prejuízo cognitivo. Quanto à trajetória do CCL, independentemente da heterogeneidade observada, os participantes com CCL do tipo Alzheimer apresentaram risco significativamente maior de desenvolver demência na DA, demonstrando o impacto do uso destes critérios que enfatizam o comprometimento da memória episódica de longo prazo e buscam identificar sujeitos com maior probabilidade de ser portadores de patologia Alzheimer. / Background: The increase of the rates of age-related diseases as dementia, especially Alzheimer's disease (AD), is projected with the aging of the world population. Subjects with Mild Cognitive Impairment (MCI) are considered a population at risk for developing dementia. However, MCI incidence rates and rates of conversion to dementia have shown considerable variability that could be partially attributed to characteristics of the sample and to different criteria. Objective: To determine the incidence of dementia and mild cognitive impairment in a cohort of community-based healthy elderly individuals; to determine the demographic, clinical and social variables associated with the development of cognitive impairment; and to assess the risk of progression of individuals with mild cognitive impairment to dementia compared with cognitively normal subjects. Methods: Data were derived from a cohort of elderly community residents (N = 345), who were initially healthy and independent (PALA – Porto Alegre Longitudinal Aging – study). The follow-up of a maximum of eight years was used to evaluate the incidence of AD and MCI. To evaluate the progression of MCI to dementia due to AD we set off the 10-year follow-up, including the previous 8-year of the first analysis, and consider the maximum of 70 months (mean 45 months) for these new outcomes. Participants who met the inclusion criteria of the study and consented to participate were evaluated with a detailed clinical interview consisted of demographic, clinical and social variables. Psychiatric symptoms were assessed with the SRQ scale (Self Report Questionnaire), the MADRS (Montgomery-Asberg Depression Rating Scale), and the Diagnostic and Statistical Manual of Mental Disorders (4th edition, DSM-IV) criteria for Major Depression. Cognitive assessment was checked with the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR). Independence for the activities of daily living was assessed with the ADL scale (Activities of Daily Living). Incident cases of probable Alzheimer's disease were assigned through the DSM-IV and the NINCDS-ADRDA diagnostic criteria, with the additional designation from Kawas and colleagues of consistent AD. Detection of Mild Cognitive Impairment for the first analysis was carried out with the MCI Mayo Clinic criteria. The MCI of the Alzheimer type criteria (or Prodromal AD) were used for the second analysis, incorporating available data of the sample and the ongoing evolution of the criteria. The possible MCI trajectories were classified into three categories: conversion, stabilization, and reconversion. The subjects for the first analysis – MCI and AD incidence – were the participants who had at least one follow-up visit in the 8-year period from the baseline (N = 245), and the statistical analyzes were based on the diagnosis established in last follow-up interview. For the deceased during the period, retrospective data were obtained through a telephone interview with a knowledgeable collateral source focusing on dementia. The baseline clinical and demographic data were analyzed as predictors of the study outcomes. For the second analysis – risk of MCI progression to AD, and MCI trajectories – the sample was composed of 21 individuals who developed MCI and 220 cognitively normal subjects (N = 241). Results: The results of the first analysis showed the MCI incidence rate of 13.2 per 1,000 person-years and the AD incidence of 14.8 per 1,000 person-years. The development of cognitive impairment was associated with education (odds ratio [OR] = 0.86) and baseline MMSE scores (OR = 0.81). The results of second analysis showed that of the 21 MCI subjects, 38% developed dementia, 24% remained stable, and 38% improved. The annual AD conversion rate was 8.5%, and MCI was significantly associated with increased risk of progression to AD (HR = 49.83; p = 0.004), even adjusted for age, education, gender and MMSE scores. Conclusion: The AD incidence in this sample was higher than that described in a previous study carried out in Brazil, but was within the international estimates. Lower baseline scores on the Mini Mental State Examination, although within the normal range, and lower levels of education were predictors of cognitive impairment. Regardless the observed heterogeneity of the MCI trajectories, participants with MCI of the Alzheimer type showed significantly higher risk of developing dementia due to AD, demonstrating the impact of the emphasis on the episodic long-term memory impairment of the criteria, which finally searches to identify those individuals more likely to have Alzheimer's pathology.

Introdução: Com o envelhecimento da população mundial projeta-se o crescimento das taxas de doenças potencialmente relacionadas à idade como as demências, especialmente a doença de Alzheimer (DA). Os sujeitos com Comprometimento Cognitivo Leve (CCL) são considerados uma população de risco para desenvolver demência, no entanto, as taxas de incidência de CCL e conversão para demência apresentam considerável variabilidade em parte atribuída a características da amostra e aos diferentes critérios utilizados. Objetivos: Determinar a incidência de demência e Comprometimento Cognitivo Leve em uma coorte de idosos saudáveis de base comunitária; determinar as variáveis demográficas, clínicas e sociais associadas ao desenvolvimento de prejuízo cognitivo, e avaliar o risco de progressão dos indivíduos com Comprometimento Cognitivo Leve para demência comparada com sujeitos cognitivamente normais. Métodos: Os dados foram derivados de uma coorte de idosos residentes na comunidade (N = 345), inicialmente saudáveis e independentes (Estudo PALA - Porto Alegre Longitudinal Aging - study). O seguimento inicial com duração máxima de oito anos teve o objetivo de avaliar a incidência de DA e CCL. Para avaliar a progressão de CCL para DA partimos de 10 anos de seguimento, incluindo os oito anos da primeira análise e consideramos um máximo de 70 meses (média de 45 meses) para avaliar a ocorrência dos novos desfechos. Os participantes que preencheram os critérios de inclusão do estudo e consentiram em participar foram avaliados com uma detalhada entrevista clínica composta de variáveis demográficas, clínicas e sociais. Os sintomas psiquiátricos foram avaliados pela escala SRQ - Self Report Questionnaire, escala MADRS - Montgomery-Asberg Depression Rating Scale e aplicados os critérios para depressão maior do Manual de Diagnóstico e Estatístico de Transtornos Mentais (4ª Edição; DSM-IV). O Mini Exame do Estado Mental (MEEM) e a Escala Clínica de Demência (CDR – Clinical Dementia Rating) foram aplicados para avaliação cognitiva. Adicionalmente a independência para as atividades da vida diária foram acessadas pela escala ADL - Activities of Daily Living. Para diagnóstico dos casos incidentes de doença de Alzheimer foi utilizado os critérios diagnósticos do DSM-IV e do NINCDS/ADRDA, associado à descrição dos critérios de Kawas para DA consistente. Para diagnóstico de Comprometimento Cognitivo Leve, o critério da Clínica Mayo foi aplicado para a primeira análise, e o critério para CCL do tipo Alzheimer (ou DA prodrômica) foi utilizado para a segunda análise tendo em vista a incorporação de dados disponíveis e a evolução dos critérios. As trajetórias possíveis do CCL foram classificadas em três categorias: conversão, estabilização e reconversão. Os sujeitos considerados para a primeira análise - casos incidentes de CCL e DA foram os participantes que apresentavam pelo menos uma visita de seguimento no período de oito anos a partir da linha de base (N = 245) e as análises estatísticas foram baseadas no diagnóstico estabelecido na última visita de seguimento. Para os falecidos durante o período, dados retrospectivos foram obtidos através de uma entrevista telefônica com um informante confiável. Os dados clínicos e demográficos de linha de base foram utilizados para cálculo dos fatores preditivos dos desfechos do estudo. Para a segunda análise – risco de conversão de CCL para DA – trajetórias do CCL, a amostra foi composta dos 21 indivíduos que desenvolveram CCL e 220 indivíduos cognitivamente normais (N = 241). Resultados: Os resultados da primeira análise mostraram taxa de incidência de CCL de 13,2 por 1.000 pessoas-ano e incidência de DA de 14,8 por 1.000 pessoas-ano. O desenvolvimento de prejuízo cognitivo foi associado com educação (razão de chance [RC] = 0,86) e o escore do MEEM de base (RC = 0,81). Os resultados da segunda análise mostraram que dos 21 sujeitos com CCL, 38% desenvolveram demência, 24% permaneceram estáveis e 38% melhoraram. A taxa de conversão anual para DA foi de 8,5%, CCL foi associado significativamente a maior risco de conversão para DA (HR = 49,83; p = 0,004), mesmo ajustado para idade, escolaridade, sexo e escore no MEEM. Conclusão: A incidência de DA nessa amostra foi maior do que a descrita em estudo prévio realizado no Brasil, mas está dentro da variabilidade observada internacionalmente. Escores mais baixos no Mini Exame do Estado Mental na linha de base, mesmo que dentro da normalidade, e níveis mais baixos de educação foram preditores da ocorrência de prejuízo cognitivo. Quanto à trajetória do CCL, independentemente da heterogeneidade observada, os participantes com CCL do tipo Alzheimer apresentaram risco significativamente maior de desenvolver demência na DA, demonstrando o impacto do uso destes critérios que enfatizam o comprometimento da memória episódica de longo prazo e buscam identificar sujeitos com maior probabilidade de ser portadores de patologia Alzheimer. / Background: The increase of the rates of age-related diseases as dementia, especially Alzheimer's disease (AD), is projected with the aging of the world population. Subjects with Mild Cognitive Impairment (MCI) are considered a population at risk for developing dementia. However, MCI incidence rates and rates of conversion to dementia have shown considerable variability that could be partially attributed to characteristics of the sample and to different criteria. Objective: To determine the incidence of dementia and mild cognitive impairment in a cohort of community-based healthy elderly individuals; to determine the demographic, clinical and social variables associated with the development of cognitive impairment; and to assess the risk of progression of individuals with mild cognitive impairment to dementia compared with cognitively normal subjects. Methods: Data were derived from a cohort of elderly community residents (N = 345), who were initially healthy and independent (PALA – Porto Alegre Longitudinal Aging – study). The follow-up of a maximum of eight years was used to evaluate the incidence of AD and MCI. To evaluate the progression of MCI to dementia due to AD we set off the 10-year follow-up, including the previous 8-year of the first analysis, and consider the maximum of 70 months (mean 45 months) for these new outcomes. Participants who met the inclusion criteria of the study and consented to participate were evaluated with a detailed clinical interview consisted of demographic, clinical and social variables. Psychiatric symptoms were assessed with the SRQ scale (Self Report Questionnaire), the MADRS (Montgomery-Asberg Depression Rating Scale), and the Diagnostic and Statistical Manual of Mental Disorders (4th edition, DSM-IV) criteria for Major Depression. Cognitive assessment was checked with the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR). Independence for the activities of daily living was assessed with the ADL scale (Activities of Daily Living). Incident cases of probable Alzheimer's disease were assigned through the DSM-IV and the NINCDS-ADRDA diagnostic criteria, with the additional designation from Kawas and colleagues of consistent AD. Detection of Mild Cognitive Impairment for the first analysis was carried out with the MCI Mayo Clinic criteria. The MCI of the Alzheimer type criteria (or Prodromal AD) were used for the second analysis, incorporating available data of the sample and the ongoing evolution of the criteria. The possible MCI trajectories were classified into three categories: conversion, stabilization, and reconversion. The subjects for the first analysis – MCI and AD incidence – were the participants who had at least one follow-up visit in the 8-year period from the baseline (N = 245), and the statistical analyzes were based on the diagnosis established in last follow-up interview. For the deceased during the period, retrospective data were obtained through a telephone interview with a knowledgeable collateral source focusing on dementia. The baseline clinical and demographic data were analyzed as predictors of the study outcomes. For the second analysis – risk of MCI progression to AD, and MCI trajectories – the sample was composed of 21 individuals who developed MCI and 220 cognitively normal subjects (N = 241). Results: The results of the first analysis showed the MCI incidence rate of 13.2 per 1,000 person-years and the AD incidence of 14.8 per 1,000 person-years. The development of cognitive impairment was associated with education (odds ratio [OR] = 0.86) and baseline MMSE scores (OR = 0.81). The results of second analysis showed that of the 21 MCI subjects, 38% developed dementia, 24% remained stable, and 38% improved. The annual AD conversion rate was 8.5%, and MCI was significantly associated with increased risk of progression to AD (HR = 49.83; p = 0.004), even adjusted for age, education, gender and MMSE scores. Conclusion: The AD incidence in this sample was higher than that described in a previous study carried out in Brazil, but was within the international estimates. Lower baseline scores on the Mini Mental State Examination, although within the normal range, and lower levels of education were predictors of cognitive impairment. Regardless the observed heterogeneity of the MCI trajectories, participants with MCI of the Alzheimer type showed significantly higher risk of developing dementia due to AD, demonstrating the impact of the emphasis on the episodic long-term memory impairment of the criteria, which finally searches to identify those individuals more likely to have Alzheimer's pathology.

Introdução: Com o envelhecimento da população mundial projeta-se o crescimento das taxas de doenças potencialmente relacionadas à idade como as demências, especialmente a doença de Alzheimer (DA). Os sujeitos com Comprometimento Cognitivo Leve (CCL) são considerados uma população de risco para desenvolver demência, no entanto, as taxas de incidência de CCL e conversão para demência apresentam considerável variabilidade em parte atribuída a características da amostra e aos diferentes critérios utilizados. Objetivos: Determinar a incidência de demência e Comprometimento Cognitivo Leve em uma coorte de idosos saudáveis de base comunitária; determinar as variáveis demográficas, clínicas e sociais associadas ao desenvolvimento de prejuízo cognitivo, e avaliar o risco de progressão dos indivíduos com Comprometimento Cognitivo Leve para demência comparada com sujeitos cognitivamente normais. Métodos: Os dados foram derivados de uma coorte de idosos residentes na comunidade (N = 345), inicialmente saudáveis e independentes (Estudo PALA - Porto Alegre Longitudinal Aging - study). O seguimento inicial com duração máxima de oito anos teve o objetivo de avaliar a incidência de DA e CCL. Para avaliar a progressão de CCL para DA partimos de 10 anos de seguimento, incluindo os oito anos da primeira análise e consideramos um máximo de 70 meses (média de 45 meses) para avaliar a ocorrência dos novos desfechos. Os participantes que preencheram os critérios de inclusão do estudo e consentiram em participar foram avaliados com uma detalhada entrevista clínica composta de variáveis demográficas, clínicas e sociais. Os sintomas psiquiátricos foram avaliados pela escala SRQ - Self Report Questionnaire, escala MADRS - Montgomery-Asberg Depression Rating Scale e aplicados os critérios para depressão maior do Manual de Diagnóstico e Estatístico de Transtornos Mentais (4ª Edição; DSM-IV). O Mini Exame do Estado Mental (MEEM) e a Escala Clínica de Demência (CDR – Clinical Dementia Rating) foram aplicados para avaliação cognitiva. Adicionalmente a independência para as atividades da vida diária foram acessadas pela escala ADL - Activities of Daily Living. Para diagnóstico dos casos incidentes de doença de Alzheimer foi utilizado os critérios diagnósticos do DSM-IV e do NINCDS/ADRDA, associado à descrição dos critérios de Kawas para DA consistente. Para diagnóstico de Comprometimento Cognitivo Leve, o critério da Clínica Mayo foi aplicado para a primeira análise, e o critério para CCL do tipo Alzheimer (ou DA prodrômica) foi utilizado para a segunda análise tendo em vista a incorporação de dados disponíveis e a evolução dos critérios. As trajetórias possíveis do CCL foram classificadas em três categorias: conversão, estabilização e reconversão. Os sujeitos considerados para a primeira análise - casos incidentes de CCL e DA foram os participantes que apresentavam pelo menos uma visita de seguimento no período de oito anos a partir da linha de base (N = 245) e as análises estatísticas foram baseadas no diagnóstico estabelecido na última visita de seguimento. Para os falecidos durante o período, dados retrospectivos foram obtidos através de uma entrevista telefônica com um informante confiável. Os dados clínicos e demográficos de linha de base foram utilizados para cálculo dos fatores preditivos dos desfechos do estudo. Para a segunda análise – risco de conversão de CCL para DA – trajetórias do CCL, a amostra foi composta dos 21 indivíduos que desenvolveram CCL e 220 indivíduos cognitivamente normais (N = 241). Resultados: Os resultados da primeira análise mostraram taxa de incidência de CCL de 13,2 por 1.000 pessoas-ano e incidência de DA de 14,8 por 1.000 pessoas-ano. O desenvolvimento de prejuízo cognitivo foi associado com educação (razão de chance [RC] = 0,86) e o escore do MEEM de base (RC = 0,81). Os resultados da segunda análise mostraram que dos 21 sujeitos com CCL, 38% desenvolveram demência, 24% permaneceram estáveis e 38% melhoraram. A taxa de conversão anual para DA foi de 8,5%, CCL foi associado significativamente a maior risco de conversão para DA (HR = 49,83; p = 0,004), mesmo ajustado para idade, escolaridade, sexo e escore no MEEM. Conclusão: A incidência de DA nessa amostra foi maior do que a descrita em estudo prévio realizado no Brasil, mas está dentro da variabilidade observada internacionalmente. Escores mais baixos no Mini Exame do Estado Mental na linha de base, mesmo que dentro da normalidade, e níveis mais baixos de educação foram preditores da ocorrência de prejuízo cognitivo. Quanto à trajetória do CCL, independentemente da heterogeneidade observada, os participantes com CCL do tipo Alzheimer apresentaram risco significativamente maior de desenvolver demência na DA, demonstrando o impacto do uso destes critérios que enfatizam o comprometimento da memória episódica de longo prazo e buscam identificar sujeitos com maior probabilidade de ser portadores de patologia Alzheimer. / Background: The increase of the rates of age-related diseases as dementia, especially Alzheimer's disease (AD), is projected with the aging of the world population. Subjects with Mild Cognitive Impairment (MCI) are considered a population at risk for developing dementia. However, MCI incidence rates and rates of conversion to dementia have shown considerable variability that could be partially attributed to characteristics of the sample and to different criteria. Objective: To determine the incidence of dementia and mild cognitive impairment in a cohort of community-based healthy elderly individuals; to determine the demographic, clinical and social variables associated with the development of cognitive impairment; and to assess the risk of progression of individuals with mild cognitive impairment to dementia compared with cognitively normal subjects. Methods: Data were derived from a cohort of elderly community residents (N = 345), who were initially healthy and independent (PALA – Porto Alegre Longitudinal Aging – study). The follow-up of a maximum of eight years was used to evaluate the incidence of AD and MCI. To evaluate the progression of MCI to dementia due to AD we set off the 10-year follow-up, including the previous 8-year of the first analysis, and consider the maximum of 70 months (mean 45 months) for these new outcomes. Participants who met the inclusion criteria of the study and consented to participate were evaluated with a detailed clinical interview consisted of demographic, clinical and social variables. Psychiatric symptoms were assessed with the SRQ scale (Self Report Questionnaire), the MADRS (Montgomery-Asberg Depression Rating Scale), and the Diagnostic and Statistical Manual of Mental Disorders (4th edition, DSM-IV) criteria for Major Depression. Cognitive assessment was checked with the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR). Independence for the activities of daily living was assessed with the ADL scale (Activities of Daily Living). Incident cases of probable Alzheimer's disease were assigned through the DSM-IV and the NINCDS-ADRDA diagnostic criteria, with the additional designation from Kawas and colleagues of consistent AD. Detection of Mild Cognitive Impairment for the first analysis was carried out with the MCI Mayo Clinic criteria. The MCI of the Alzheimer type criteria (or Prodromal AD) were used for the second analysis, incorporating available data of the sample and the ongoing evolution of the criteria. The possible MCI trajectories were classified into three categories: conversion, stabilization, and reconversion. The subjects for the first analysis – MCI and AD incidence – were the participants who had at least one follow-up visit in the 8-year period from the baseline (N = 245), and the statistical analyzes were based on the diagnosis established in last follow-up interview. For the deceased during the period, retrospective data were obtained through a telephone interview with a knowledgeable collateral source focusing on dementia. The baseline clinical and demographic data were analyzed as predictors of the study outcomes. For the second analysis – risk of MCI progression to AD, and MCI trajectories – the sample was composed of 21 individuals who developed MCI and 220 cognitively normal subjects (N = 241). Results: The results of the first analysis showed the MCI incidence rate of 13.2 per 1,000 person-years and the AD incidence of 14.8 per 1,000 person-years. The development of cognitive impairment was associated with education (odds ratio [OR] = 0.86) and baseline MMSE scores (OR = 0.81). The results of second analysis showed that of the 21 MCI subjects, 38% developed dementia, 24% remained stable, and 38% improved. The annual AD conversion rate was 8.5%, and MCI was significantly associated with increased risk of progression to AD (HR = 49.83; p = 0.004), even adjusted for age, education, gender and MMSE scores. Conclusion: The AD incidence in this sample was higher than that described in a previous study carried out in Brazil, but was within the international estimates. Lower baseline scores on the Mini Mental State Examination, although within the normal range, and lower levels of education were predictors of cognitive impairment. Regardless the observed heterogeneity of the MCI trajectories, participants with MCI of the Alzheimer type showed significantly higher risk of developing dementia due to AD, demonstrating the impact of the emphasis on the episodic long-term memory impairment of the criteria, which finally searches to identify those individuals more likely to have Alzheimer's pathology.

Ce travail de thèse s’intéresse à la Théorie de l’Esprit (TdE) dans les stades précoces de la maladie d’Alzheimer (MA) et le Mild Cognitive Impairment (MCI). La TdE est un processus central de la cognition sociale permettant d’inférer les états mentaux d’autrui et de nous adapter aux interactions sociales auxquelles nous sommes confrontés chaque jour. Des travaux ont mis en évidence un déficit de TdE chez le patient MA mais son authenticité reste discutée et celui-ci est attribuer aux autres troubles cognitifs des patients. Par ailleurs, une seule étude à ce jour s’était intéressée à la TdE chez le patient MCI, laissant un champ d’étude inexploré malgré l'intérêt de cet état pour le diagnostic précoce des pathologies dégénératives. Ce travail a pour but d’approfondir les données existantes sur le fonctionnement de la TdE dans la MA et le MCI et présente également l’ambition d’évaluer, pour la première fois dans ces populations, la TdE au plus près de son fonctionnement quotidien dans une tâche impliquant le patient dans une vraie interaction sociale. Les résultats montrent que les patients présentent bien un déficit de TdE y compris sur la tâche immersive, suggérant que ce déficit est observable dans des situations proches de la vie quotidienne. Les patients présentent également un déficit sur une tâche plus classique de TdE, la nature de leurs erreurs témoignant de l’authenticité de ce déficit. Ce travail tend donc à confirmer la présence d’un dysfonctionnement de la TdE dans les stades débutants de la MA et dans le MCI. Ce déficit est précoce, authentique et observé pour la première fois dans une situation d’interaction sociale réelle. / This work investigates Theory of Mind (ToM) ability in early Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). ToM is a core feature of social cognition allowing us to infer and understand other’s mental states (i.e. beliefs, intentions, knowledge), in order to adapt our behavior in everyday social interactions. Previous works evidenced ToM deficit in AD patients, but the authenticity of this deficit is still debated and is attributed to other cognitive dysfunctions of patients. Moreover, only one study investigated ToM in MCI. This area thus requires further investigation since MCI represents an interesting concept for early diagnosis of neurodegenerative disorders. The purpose of this work is to further investigate ToM functioning in both AD and MCI with the ambition to evaluate for the first time ToM in close-to-everyday conditions with a task involving the patient in a real interaction. Results show that patients present ToM impairment even in a real interactive task suggesting that this deficit is noticeable in naturalistic conditions closed to everyday interactions. Patients also present difficulties in a classical ToM task, the nature of their errors suggesting genuine ToM difficulties. This work therefore confirms the presence of a ToM impairment in early AD and MCI. This impairment is precocious, authentic and is observed for the first time in a real social interaction.

Le premier objectif de cette thèse était d’explorer l’effet de référence à soi (ERS) sur la mémoire dans le vieillissement, l’amnestic Mild Cognitive Impairment (aMCI) et la maladie d’Alzheimer (MA) à un stade précoce de l’évolution. Le second fut de revisiter les théories actuelles pour expliquer ce bénéfice mnésique, puis de tenter d’élucider ses mécanismes. Nous avons montré que l’ERS sur les représentations sémantiques de ses propres traits de personnalité (qui est une composante de notre identité) était préservé dans le vieillissement. Par ailleurs, nous avons montré que la profondeur de traitement, longtemps considérée comme le processus sous-tendant l’ERS, n’intervenait pas dans ce dernier. A contrario, l’interaction de l’âge et de l’estime de soi, ainsi que les expériences de vie des individus modulaient l’ERS. Nous avons montré que l’ERS pouvait résulter de deux processus : celui de la consistance des traits de caractère et celui de l’élaboration automatique des traits de caractère avec l’identité des individus. Nous avons par ailleurs rapporté pour la première fois que ce bénéfice mnésique s’opérait chez des patients atteints d’aMCI, un stade symptomatique et pré-démentiel de la MA, et qu’il pouvait s’observer dans une moindre mesure chez des patients MA. En outre, l’ERS agit comme mécanisme de self-défense chez les patients aMCI et MA, en les protégeant d’informations menaçantes pour l’intégrité de leur soi. Nous suggérons en dernier lieu que la référence à soi pourrait servir d’outil de réhabilitation sociale ou clinique pour augmenter l’estime de soi de certains individus et préserver leur mémoire et leur bien-être. / The first aim of this thesis was to examine the self-reference effect (SRE) on memory in aging, amnestic mild cognitive impairment (aMCI) and early-stage of Alzheimer’s disease (AD). The second aim was to review the whole literature on the SRE and to attempt understanding its mechanisms. We showed that the SRE on semantic summary representations of one’s traits (which is a component of identity) was preserved in aging. Besides, we showed that depth of processing, which was hitherto regarded as the mechanism responsible for the SRE, did not actually play a role in the latter. By contrast, the interaction of age and self-esteem, as well as individuals’ life experiences modulated the SRE. We showed that the SRE resulted from two processes: the congruency of traits as well as the elaboration of traits with individuals’ identity. We also reported for the first time that aMCI patients benefited from the SRE, as well as AD patients in the early stage of the disease to a lesser extent. Furthermore, the SRE acted as a self-defense mechanism in patients with aMCI and AD by protecting them from negative feedback that constituted a threat to the integrity of their selves. Finally, we suggest that referencing the self could serve as a tool for social or clinical rehabilitation programs, by increasing the self-esteem of some individuals and preserving their memory and well-being.