Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI). Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were ≥24 in all cases. The discrepancy between the patients’ and caregivers’ estimations of impairments was taken as a measure of anosognosia. Results: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). Conclusions: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver’s assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE ≥24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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.

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.

No description available.

No description available.

Retinal nerve fiber layer measurement in patients with Alzheimer's disease The current ophthalmologist's possibilities in diagnostics of Alzheimer's disease Alzheimer disease (AD) is the most common cause of dementia syndrome and mild cognitive impairment. To enroll the disease most securely there are used so called biomarkers using evidence of changed brain metabolism by pozitron emission tomography (PET) and in cerebrospinal fluid or the brain's structure magnetic resonance imaging (MRI). These methods are expensive, organisationally and temporally challenging and burdening for the patients. According to that reasons we are still seeking for alternative attitudes suitable for early diagnosis. The evaluation of thickness of retinal nerve fiber layer (RNFL) which is well accessible to examination through optical aparatus of the eye could be one of the options. The aim of our work was to present current knowledges about Alzheimer's disease targeting relations of Alzheimer's disease and an ophthalmological finding. In the next part of this paper we introduce the retinal nerve fiber layer measurement by optical coherence tomography (OCT) as a potential diagnostics method by screening of patients with Alzheimer's disease and to present our results measured in our cohort of patients. The studied cohort...

Les modifications de la morphologie du cortex cérébral induites par la maladie d'Alzheimer à ses stades précoces contribuent à l'intérêt croissant à l'égard des biomarqueurs de la morphologie corticale. Ceux-ci permettraient notamment une meilleure compréhension de l'impact de cette pathologie sur l'anatomie cérébrale et une détection plus précoce de la maladie. L'originalité de notre travail par rapport au reste de la littérature est de s'intéresser à la morphologie des surfaces interne (interface substance blanche / substance grise) et externe (interface substance grise / liquide cérébro-spinal) du cortex cérébral. Dans cette perspective, nous avons développé des méthodes d'estimation de la courbure et de la dimension fractale des surfaces corticales. A partir de ces biomarqueurs morphologiques et de l'épaisseur corticale dont la méthode d'estimation a été précédemment développée dans le laboratoire, nous avons exploré l'impact de la maladie d'Alzheimer sur la morphologie du manteau cortical et nous avons évalué leur apport individuel et celui de leur association au diagnostic précoce de la maladie. Nos résultats montrent une influence significative de la pathologie sur la morphologie des sillons et sur celle des circonvolutions des surfaces corticales interne et externe. En termes d'application diagnostique, nous montrons que prises isolément, l'épaisseur corticale présente une meilleure capacité prédictive que la courbure corticale, nous ne constatons en revanche aucune capacité prédictive de la dimension fractale. Par contre, nous montrons que l'utilisation conjointe de l'épaisseur corticale et de la courbure permet une amélioration significative du diagnostic précoce. / Morphological alterations of the cortical mantle in early stage of Alzheimer's disease have led to an increasing interest towards morphological biomarkers of the cerebral cortex. By providing a quantitative measure of the cortical shape, morphological biomarkers could provide better understanding of the impact of the disease on the cortical anatomy and play a role in early diagnosis. Therefore, as a primary goal in this study, we developed cortical surface curvature and fractal dimension estimation methods. We then applied those methods, together with the estimation of cortical thickness, to investigate the impact of Alzheimer's disease on the cortical shape as well as the contribution of cortical thickness and cortical curvature to the early diagnosis of Alzheimer's disease. The originality of this work lies in the estimation of sulcal and gyral curvature of the internal (gray matter/white matter boundary) and external (gray matter/cerebrospinal fluid boundary) cortical surfaces in addition to the fractal dimensions of these boundaries. Our results showed significant impact of Alzheimer's disease on sulcal and gyral shapes of the internal and external cortical surfaces. In addition, cortical thickness was found to have better ability than cortical curvature for the early diagnosis of Alzheimer's disease; no significant ability for the early diagnosis was found using fractal dimension. However, we found significant improvement in early diagnosis by combining cortical thickness and cortical curvature.

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-06-08T11:55:52Z No. of bitstreams: 1 DissFAAM.pdf: 2168613 bytes, checksum: c80ea0c2ce14ed6b12536e4420bd312e (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-13T18:03:42Z (GMT) No. of bitstreams: 1 DissFAAM.pdf: 2168613 bytes, checksum: c80ea0c2ce14ed6b12536e4420bd312e (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-13T18:03:48Z (GMT) No. of bitstreams: 1 DissFAAM.pdf: 2168613 bytes, checksum: c80ea0c2ce14ed6b12536e4420bd312e (MD5) / Made available in DSpace on 2017-06-13T18:12:18Z (GMT). No. of bitstreams: 1 DissFAAM.pdf: 2168613 bytes, checksum: c80ea0c2ce14ed6b12536e4420bd312e (MD5) Previous issue date: 2017-02-23 / Outra / Background: Little is known about how the change in walking speed in longitudinal studies can predict the occurrence of falls in older adults with mild cognitive impairment. Objetives: To identify if there are differences in the gait speed of Cognitively Preserved (CPr) elderly persons, elderly persons with Mild Cognitive Impairment (MCI) and with Alzheimer`s Disease (AD) in mild stage, in a 6-month period. To verify if the change in the gait speed (ΔGS= Final Gait speed – Initial Gait speed) predicts the occurrence of falls in elderly with MCI and AD in mild stage. Methods: 110 elderly people participated in the study. Out of these: 40 with CPr, 36 with MCI and 34 with AD in the mild stage. Initially the 10-meter walk test was applied and a fall schedule was given. A 6-month follow-up was carried out, by means of monthly telephone calls to the volunteers and the filling of a fall schedule. After six months, the 10-meter walk test was applied and the fall schedule was retrieved. Results: The MCI and AD groups of elderly in mild stage presented lower gait speed compared to the elderly in the CPr group at the two assessment moments. There was no significant difference in delta gait speed amongst the groups. In the age-adjusted univariate logistic regression analysis, the delta failed to predict falls in the elderly with MCI or in elderly with AD. Conclusion: Older adults with MCI and AD in the mild stage were identified as having lower gait speed compared to CPr sujeitos. Changing in the gait speed over a six-month period does not predict the occurrence of falls in elderly with MCI or AD in mild stage. / Contextualização: Pouco se tem conhecimento sobre como a mudança da velocidade da marcha em estudos longitudinais, pode predizer a ocorrência de quedas em idosos com comprometimento cognitivo em estágios iniciais. Objetivos: a) identificar se há diferenças na velocidade da marcha entre idosos preservados cognitivamente (PrC) com transtorno neurocognitivo leve (TNL) e com doença de Alzheimer (DA) na fase leve ao longo de seis meses; b) Verificar se a mudança da velocidade da marcha (ΔVM= velocidade final - velocidade inicial) prediz a ocorrências de quedas em idosos com TNL e DA nesse período. Método: Participaram do estudo 110 idosos. Destes 40 PrC, 36 com TNL e 34 com DA. Inicialmente foi aplicado o teste de caminhada de 10 metros e entregue um calendário de quedas. Realizou-se um seguimento de seis meses por meio de ligações mensais para os voluntários e preenchimento do calendário de quedas. Após seis meses, aplicou-se novamente o teste de caminhada e o calendário de quedas foi resgatado. Resultados: Os idosos dos grupos com TNL e com DA apresentaram velocidades de marcha menor quando comparados com os idosos do grupo PrC, nos dois momentos de avaliação (p<0,001). Não houve diferença significativa no delta da velocidade da marcha entre os grupos (p=0,063). Na análise de regressão logística univariada, ajustado para idade, o ΔVM não conseguiu predizer quedas em idosos com TNL (p=0,185) nem em idosos com DA (p=0,232). Conclusão: Identificou-se que os idosos com TNL e DA na fase leve tem velocidades da marcha menores quando comparados com idosos PrC. A mudança da velocidade da marcha em um período de seis meses não prediz a ocorrência de quedas em idosos com TNL, nem idosos com DA na fase leve.

Submitted by Aelson Maciera (aelsoncm@terra.com.br) on 2017-06-26T17:52:34Z No. of bitstreams: 1 TeseJHA.pdf: 1814260 bytes, checksum: 140f576789c3cbb7e3aa416fc5dc4416 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-27T19:44:07Z (GMT) No. of bitstreams: 1 TeseJHA.pdf: 1814260 bytes, checksum: 140f576789c3cbb7e3aa416fc5dc4416 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-27T19:45:05Z (GMT) No. of bitstreams: 1 TeseJHA.pdf: 1814260 bytes, checksum: 140f576789c3cbb7e3aa416fc5dc4416 (MD5) / Made available in DSpace on 2017-06-27T19:52:05Z (GMT). No. of bitstreams: 1 TeseJHA.pdf: 1814260 bytes, checksum: 140f576789c3cbb7e3aa416fc5dc4416 (MD5) Previous issue date: 2017-03-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introduction: Recent studies reported mobility deficits and higher prevalence of falls in older people with cognitive impairment, even in mild stages of impairment. However, differences in mobility during simple and dual task situations between older people with preserved cognition (PC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (mild stage) are still not clear. Sophisticated mobility tools and dual task activities with new, functional and challenging secondary tasks could be effective in identifying subtle motor changes. Moreover, a better understanding about the relationship between cognitive and motor changes and the fall risk factors in older people with MCI and AD could provide new knowledge about the physiopathology of MCI and AD and could help in better planning of screening, prevention and interventions of falls, MCI and AD. Objective: to analyze mobility, functional dual task and falls in older people with PC, MCI and mild AD. Method: The sample was composed by 40 community-dwelling older people with PC, 40 MCI and 38 mild AD. All volunteers performed an assessment, including anamneses, history of falls in the past year, cognition (Addenbrooke’s cognitive Examination-revised version and Frontal Assessment Battery), dual task (Timed up and go test-TUG associated with the motor-cognitive task of calling a phone number) and functional mobility (10-meter walk test and TUG). The TUG phases (sit-to-stand, walking forward, turn, walking back and turn-to-sit) were assessed using a system of movement analysis (Qualisys motion system). Still, the occurrence of falls was collected prospectively in a 6-month follow up using falls calendar and monthly calls in older people with MCI and AD. Sociodemographic and clinical, level of physical activity, functional status, functional mobility, cognitive and depressive variables were analyzed as potential fall risk factors. For statistical analysis, a significance level of α=0.05 was adopted and the SPSS software was used (20.0). Results: Older people with cognitive impairment (MCI and mild AD) presented more falls (retrospective data) compared to people with PC, and specific characteristics (place, consequences) about history of falls between groups were identified. Regarding dual task and 10-meter walk tests, only measures of dual task test distinguished older people with mild AD from PC and MCI and no measure could differ MCI and PC groups. In relation to functional mobility (kinematic data), all TUG phases could differentiate older people with AD from PC, except the sit-to-stand phase. The walking forward phase differed older people with PC from MCI, specifically on range of motion variables during stance phase. The walking back, turn and turn-to-sit phases distinguished older subjects with AD from MCI. Regarding the association between cognitive domains and mobility, different cognitive domains predicted the 10-meter walk test and the isolated cognitive-motor task measures among groups. The visuospatial domain was independently associated with TUG (total time) in MCI and AD groups and with the dual task test in all three groups. No significant associations were found between the walking TUG phases and cognitive domains in any group. However, executive function deficits was associated with impairments of transition TUG phases in the three groups. The visuospatial domain was identified as an independent predictor of turn-to-walk and turn-to-sit measures in the AD Group. During the 6-month follow-up, 52,6% of MCI people and 51,4% of AD people fell at least once. After multivariate analysis, the dual task test and the turn-to-sit phase were able to independently predict falls in older people with MCI and AD, respectively. Conclusion: The dual task test used was able to distinguish older people with AD from PC and MCI. The analysis of transition and also the walking TUGT phases separately is essential in the identification of mobility patterns among cognitive profiles of older people. Still, the findings demonstrate the importance of considering the influence of specific cognitive domains in daily mobility tasks in order to improve rehabilitation and prevention of cognitive and mobility disturbances. The prediction of visuospatial domain on postural transition tasks may provide insight into why people with AD have an elevated fall risk. The modifiable fall risk factors found can be used to detect risk of falls, as well as improving interventions for preventing falls in older adults with MCI and AD, with focus on exercises involving dual task and transition postural activities. / Introdução: Estudos recentes identificaram prejuízos em tarefas de mobilidade e maior prevalência de quedas em idosos com comprometimento cognitivo, mesmo em estágios leves. Porém, as diferenças na mobilidade em situações simples e de dupla tarefa entre idosos preservados cognitivamente (PC), com comprometimento cognitivo leve (CCL) e doença de Alzheimer (DA) na fase leve ainda não são claras. Nesse sentido, instrumentos sofisticados que avaliem a mobilidade e atividades de dupla tarefa com tarefas secundárias funcionais e desafiadoras podem ser sensíveis para identificar pequenas mudanças motoras. Ainda, um melhor entendimento da relação existente entre as alterações cognitivas e motoras e os fatores de risco a quedas em idosos com CCL e DA forneceriam novos conhecimentos dos distúrbios e poderiam auxiliar em melhoras no planejamento do rastreio e tratamento de CCL, DA e quedas em idosos. Objetivo: Analisar a mobilidade, dupla tarefa funcional e quedas em idosos preservados cognitivamente, com CCL e DA na fase leve. Método: A amostra foi composta por 40 idosos da comunidade PC, 40 CCL e 38 DA na fase leve. Todos os sujeitos participaram de uma avaliação, com os seguintes itens: anamnese, histórico de quedas no último ano, cognição (Bateria de Avaliação Frontal e Exame Cognitivo de Addenbrooke-versão revisada), dupla tarefa (teste Timed up and go-TUG associado à tarefa cognitivo-motora de discar um número de telefone) e mobilidade funcional (teste de velocidade de marcha de 10 metros e teste TUG). As fases do teste TUG levantar-se, marcha ida, retornar, marcha volta e virar-se para sentar foram avaliadas a partir do sistema de análise de movimento Qualisys motion system. Ainda, a ocorrência de quedas foi coletada ao longo de seis meses por meio de calendário e telefonemas mensais nos Grupos CCL e DA. Variáveis sociodemográficas e clínicas, gasto calórico semanal, status funcional, mobilidade funcional, cognição e depressão foram analisadas como potenciais fatores de risco para quedas. Para análise estatística, adotouse um nível de significância de α = 0,05 e utilizou-se o software SPSS (20.0). Resultados: Os idosos com distúrbio cognitivo (CCL e DA leve) apresentaram mais quedas (dados retrospectivos) quando comparados a idosos PC, e características específicas das quedas (local, consequências) entre os grupos foram identificadas. Quanto aos testes de dupla tarefa e velocidade de marcha, somente medidas do teste de dupla tarefa distinguiram idosos com DA leve de PC e CCL e nenhuma medida conseguiu diferir os grupos CCL e PC. Em relação à mobilidade funcional (dados cinemáticos), todas as fases do TUG conseguiram diferenciar idosos com DA de PC, exceto a fase levantar-se. A fase marcha ida diferiu idosos PC de CCL, especificamente em variáveis de amplitude de movimento durante a fase de apoio da marcha. As fases marcha volta, retornar e virar-se para sentar diferiram idosos com DA de CCL. A respeito da associação entre domínios cognitivos e mobilidade, diferentes domínios cognitivos previram as medidas dos testes velocidade de marcha de 10 metros e tarefa cognitivo-motora isolada entre os grupos estudados. O domínio visuo-espacial foi independentemente associado com o TUG (tempo total) nos grupos CCL e DA e com o teste de dupla tarefa nos três grupos. Não houve associação significativa entre as fases de marcha do TUG e os domínios cognitivos em nenhum grupo. No entanto, déficit nas funções executivas foi associado com prejuízo nas fases de transição do TUG nos três grupos. O domínio visuo-espacial foi identificado como um preditor independente das medidas das fases retornar e virar-se para sentar no Grupo DA. Durante o seguimento de seis meses, 52,6% das pessoas com CCL e 51,4% de DA caíram. Após análise multivariada, o teste de dupla tarefa e a fase virar-se para sentar do TUG foram capazes de predizer quedas de forma independente em idosos com CCL e DA leve, respectivamente. Conclusão: O teste de dupla tarefa utilizado foi capaz de distinguir idosos com DA de PC e CCL. Não somente as fases de transição do TUG, como também as análises das fases de marcha separadamente, são essenciais na diferenciação dos padrões de mobilidade entre perfis cognitivos de idosos. Ainda, os achados demonstram a importância de considerar a influência de domínios cognitivos específicos em tarefas de mobilidade do dia a dia a fim de melhorar o rastreio e a reabilitação de distúrbios cognitivos e de mobilidade. A predição do domínio visuoespacial em tarefas de transição postural pode fornecer novas informações sobre os motivos do maior risco de quedas em DA. Os fatores de risco modificáveis encontrados no trabalho podem ser usados para detectar o risco de quedas, assim como melhorar intervenções para prevenir quedas em idosos com CCL e DA, com o enfoque em exercícios envolvendo atividades de dupla tarefa e de transição postural.

Cognitive impairment is considered as essential feature of non-motor symptoms in Parkinson's disease (PD). It is a result of underlying pathological processes in the brain of PD patients and it leads to decreased quality of life. In this thesis an analysis of the structure and profile of cognitive impairment is presented with special emphasis on executive functions and memory. We take diagnostic entities developed for the description of PD cognitive spectrum such as mild cognitive impairment (PD-MCI) and dementia (PD-D) as examples of heterogeneity and different severity of cognitive impairment in PD. However, neuropsychological methods in Czech version that would measure these diagnotic units were not adequatly validated. In the experimental part we test a hypothesis, if gait disorder with falls in PD is interconnected with cognitive impairment, and if PD-fallers have more severe cognitive deficit than PD-non-fallers. On the basis of nine validity or normative data studies we show psychometric properties and clinical utility of several basic neuropsychological methods in the Czech population for memory (Rey Auditory Verbal Learning Test, California Verbal Learning Test, Second Edition, Memory For Intentions Screening Test and Enhanced Cued Recall Test), sustained attention and executive functions...