The absence of gold standard criteria for mild cognitive impairment (MCI) impedes the comparison of research findings and the development of primary and secondary prevention strategies addressing the possible conversion to dementia. The objective of Study 1 was to compare the predictive ability of different MCI models as markers for incipient dementia in a longitudinal population-based Canadian sample. The utility of well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA) was examined. Demographic characteristics, average neuropsychological test performance, and prevalence and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest prevalence and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia five years later was the Cognitive Impairment, No Dementia (CIND) Type 2 case definition. It is estimated that more restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning to dementia. Using data from the CSHA, the objective of Study 2 was to elucidate the clinical correlates that best differentiate between cognitive classifications. A machine learning algorithm was used to identify the symptoms that best discriminated between: 1) not cognitively impaired (NCI) and CIND; 2) CIND & demented; and 3) converting and non-converting CIND participants. Poor retrieval was consistently a significant predictor of greater cognitive impairment across all three questions. While interactions with other predictors were noted when differentiating CIND from NCI and demented from non-demented participants, retrieval was the sole predictor of conversion to dementia over five years. Importantly, the limited specificity and predictive values of the respective algorithms caution against their use as clinical markers of CIND, dementia, or conversion. Rather, it is recommended that the predictors serve as markers for ongoing monitoring and assessment. Overall, the results of both studies suggest that the architecture of pathological cognitive decline to dementia may not be captured by a single set of diagnostic criteria.

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.

Dans le contexte du diagnostic précoce de la maladie d’Alzheimer, une direction de la recherche émerge autour de l’informatisation de tests cognitifs. Nous avons conçu un test de barrage informatisé sur tablette (test e-CT), développé à partir d’un test de barrage papier-crayon. Nous avons étudié les variables influençant les performances au test e-CT et ses propriétés psychométriques. Nous avons observé que chez les sujets âgés sains, la seule variable influençant était l’âge. Les performances au test e-CT n’étaient pas influencées par l’expérience avec un appareil informatique. Cependant, chez les patients présentant des troubles cognitifs, ceux qui utilisaient quotidiennement un appareil informatique avaient une meilleure performance que ceux qui n’avaient pas un usage quotidien. En effet, les patients utilisant quotidiennement un appareil informatique présentaient de meilleures capacités cognitives. Le test e-CT était corrélé avec plusieurs tests des fonctions exécutives (validité convergente), mais pas avec le test de la mémoire épisodique (validité divergente). Il présente aussi une bonne fidélité test-retest. Le test e-CT présente des bonnes performances diagnostiques, permettant de différencier les personnes âgées saines des patients présentant des troubles cognitifs. En conclusion, le test e-CT présente des propriétés psychométriques satisfaisantes et peut être utilisé pour l’évaluation cognitive chez le sujet âgé. / In the context of early detection of cognitive impairment associated with dementia, an area of research focus concerns development and validation of computerized tests. We have developed a tablet-based cancellation test (e-CT), based on an existing paper-and-pencil cancellation test (K-T test). We studied the variables influencing performance on the e-CT and its psychometric properties. Among healthy older adults, only age was found to be an influencing variable. The performance on the e-CT was not influenced by experience with a computer-based device. However, for patients suffering from cognitive impairment, those using a computer-based device daily outperformed those who were not daily users. Further analyses showed that daily users conserved better cognitive capacities than non-daily users. The e-CT showed significant correlations with several measures of executive functions (convergent validity), but there was no relationship between the e-CT and the episodic memory test (divergent validity). It showed good test-retest reliability. The e-CT had good diagnostic accuracy in differentiating between healthy elderly subjects and patients with cognitive impairment. In conclusion, the e-CT test shows satisfying psychometric properties and is a promising tool for neuropsychological assessment in older adults

Les hypersignaux de la substance blanche (HSB) ont été associés à des déficits exécutifs et mnésiques et à une atteinte des circuits corticaux et sous-corticaux frontaux. Leur présence, en plus du dépôt ß-amyloïde chez de nombreux patients avec un MCI (Mild Cognitive Impairment ou trouble cognitif léger) augmenterait le risque de conversion vers une maladie d'Alzheimer (MA). Un des enjeux importants dans la phase préclinique de la maladie est d'explorer le potentiel des interventions cognitives pour prévenir le déclin cognitif et la progression vers une MA. Alors que les HSB sont de plus en plus considérés comme un des facteurs déterminant l'hétérogénéité des patients MCI, peu d'étude ont pris en compte leur présence dans les interventions cognitives. L'hypothèse qu'une intervention pourrait induire des effets différentiels selon l'existence ou non d'hypersignaux dans le MCI reste inexplorée à notre connaissance, et est au cœur de ce travail de thèse. / White matter hyper signals (WMH) were associated with executive and memory deficits and impairment of the cortical and subcortical frontal circuits. Their presence, in addition to amyloid deposition in many patients with Mild Cognitive Impairment (MCI), would increase the risk of conversion to Alzheimer's disease (AD). An important issues in the preclinical phase of MCI is to explore the potential of cognitive interventions to prevent cognitive decline and progression to AD. While WMH are increasingly considered as one of factors determining the heterogeneity of MCI patients, few studies have take into account their presence in cognitive interventions. The hypothesis that an intervention could induce differential effects according to the existence or not of WMH in MCI remains unexplored to our knowledge, and is at the heart of this work of thesis.

No description available.

The overall aim was to improve knowledge of the consequences of cognitive dysfunction in everyday life and of instruments to make these assessments. The thesis contains four studies each of different design using different populations. In study I, the relationship between cognitive function, ability to perform activities of daily living and perceived health-related quality of life were investigated in a population of 85-year-old individuals in the community of Linköping (n = 373). The study was part of the Elderly in Linköping Screening Assessment 85 (ELSA 85). Even mild cognitive dysfunction correlated with impaired ability to perform activities of daily living and lower health-related quality of life. In study II, the diagnostic accuracy and clinical utility of Cognistat, a cognitive screening instrument, were evaluated for identifying individuals with cognitive impairment in a primary care population. Cognistat has relatively good diagnostic accuracy with a sensitivity of 0.85, a specificity of 0.79 and a Clinical Utility Index (CUI) of 0.72. The corresponding values were 0.59, 0.91 and 0.53 for the Mini Mental State Examination (MMSE), and 0.26, 0.88 and 0.20 for the Clock Drawing Test (CDT). In study III, the aim was to develop an instrument measuring self-perceived or caregiver reported ability to perform everyday life activities in persons with suspected cognitive impairment or dementia and to perform psychometric testing of this instrument, named the Cognitive Impairment in Daily Life (CID). The CID was found to have good content validity. In study IV, experiences of cognitive impairment, its consequences in everyday life and the need for support in persons with mild cognitive impairment (MCI) or mild dementia and their relatives were explored. Interviews were performed with five people with MCI, eight people with mild dementia and their relatives (n = 13). The main finding was that persons with MCI and dementia experienced cognitive changes that could be burdensome and result in changed activity patterns. In conclusion, the findings support earlier research and show that cognitive dysfunction even at mild stages has an impact on everyday life and reduces perceived quality of life. To improve interventions for persons with cognitive impairment, it is important to assess not only cognitive function but also its consequences in everyday life activities.