INTRODUÇÃO: Os polimorfismos do gene da proteína priônica (PRNP) podem estar associados a doenças neurológicas não priônicas. Estudos em pacientes com doença de Alzheimer (DA) apontam para possível associação entre os polimorfismos do códon 129 do PRNP e DA. Essa associação não foi estudada na população brasileira. Neste estudo, descrevemos a associação entre os diferentes polimorfismos do PRNP e DA. MÉTODOS: Foi estudada amostra composta por 100 pacientes com DA, acompanhados no Ambulatório de Neurologia Cognitiva e do Comportamento e no Centro de Referência em Distúrbios Cognitivos do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, pareados para grupo controle com 111 indivíduos, em relação à frequência dos diferentes polimorfismos do PRNP e o desempenho cognitivo. Os polimorfismos do PRNP foram estudados pelo método de cromotografia líquida de fase reversa desnaturante (DHPLC). Foi realizada extratificação da amostra pelo genótipo da apolipoproteína E (apoE). RESULTADOS: A frequência dos polimorfismos do códon 129 foi: 45,5% M/M, 42,4% M/V e 12,2% V/V nos pacientes com DA; e 39,6% M/M, 50,5% M/V e 9,9% V/V nos indivíduos controles (p=0,503). O códon 117 apresentou variante alélica silenciosa em 5% dos pacientes com DA e 3% dos controles (p=0,780). A deleção de um ocatapeptídeo repetido ocorreu em 5% dos pacientes com DA e 4% dos controles (p=0,738). Todos os pacientes com DA e os controles eram N171N. Uma paciente do grupo com DA apresentou a mutação V180I. A análise bivariada e regressão logística não mostraram associação entre os diferentes polimorfismos do códon 129 e o desempenho cognitivo nos pacientes com DA, assim como nos indivíduos cognitivamente normais. A extratificação segundo genótipo da apoE não revelou diferença em relação aos polimorfismos do códon 129 do PRNP entre os grupos DA e controles. CONCLUSÕES: Não houve diferença de frequência dos diferentes polimorfismos do códon 129 do PRNP entre os pacientes com DA e idosos cognitivamente normais, bem como em relação aos demais códons polimórficos do gene. Não houve diferença em relação ao desempenho cognitivo nos pacientes com DA e nos controles segundo o polimorfismo do códon 129 do PRNP. Um paciente apresentou mutação do códon 180 (V180I), e recebeu o diagnóstico de doença de Creutzfeldt-Jakob genética / INTRODUCTION: The polymorphism in the prion protein gene (PRNP) may influence non prion neurological diseases. Some reports associate Alzheimers disease (AD) and the polymorphic codon 129 of the PRNP. This association has not been studied in Brazilian population. In this study we aimed to describe the association between the polymorphisms of codon 129 of the PRNP and AD. METHODS: One hundred AD patients were evaluated in the Cognitive and Behavioral Neurology Unit and Cognitive Disorders Reference Center of the Hospital das Clínicas of the University of São Paulo School of Medicine, matched for 111 controls, regarding to the PRNP polymorphism and cognitive measures. The PRNP polymorphisms were analyzed using denaturing high-performance liquid chromatography (DHPLC). Analyzes stratifying by apoE genotype was performed. RESULTS: The distribution of the codon 129 polymorphisms were: 45.5% M/M, 42.4% M/V and 12.2% V/V in AD patients; 39.6% M/M, 50.5% M/V and 9.9% V/V in the control group (p=0.503). The 117 codon analysis revealed silent allelic variant in 5% of AD patients and 3% of controls (p=0.780). The octarepeat deletion occurred in 5% of AD and 4% of controls (p=0.738). All AD patients and controls were N171N. One AD patient had a point mutation at codon 180 (V180I). Logistic regression failed to confirm any association between AD cognitive performance and the codon 129 of PRNP, as well as in the control group. There was no association between the codon 129 genotypes and genotypes and AD according to the apoE stratification. CONCLUSIONS: There were no differences in the frequency of the codon 129 polymorphism between AD. control group, according to the codon 129 polymorphisms. A point mutation at the codon 180 (V180I) was diagnosed in one patient

<p>Skrivning är en biomekaniskt invecklad process som kräver en viss nivå av såväl motorisksom kognitiv förmåga. Forskning om Alzheimers sjukdom tyder på att nedsättningar i flerakognitiva domäner förekommer innan den kliniska diagnosen ställs. Det finns även forskningsom tyder på att ett innehållsrikt skriftspråk i unga år minskar risken för demensutveckling påäldre dagar. För att studera om mått från texter kunde predicera demens på ett tidigt stadiumanalyserades 141 skriftliga bildbeskrivningar insamlade inom ramen för rutinmässigaminnesutredningar vid Karolinska universitetssjukhuset, Huddinge. Deltagarna delades in itre grupper utifrån diagnos (minnesutredning, lindrig kognitiv svikt och demens).Utgångspunkt för studien var de fyra textmåtten: idétäthet, verbtäthet, läsbarhetsindex (LIX)och T-enheter. Då texterna i de flesta fall var skrivna av personer med kognitiv nedsättninghar måtten varit tvungna att modifieras och särskilda instruktioner för bedömning av texternahar utformats. Resultaten tyder på att skriftliga bildbeskrivningar utförda av individer meddemens innehåller färre totalt antal ord än de skrivna av individer diagnostiserade medlindrig kognitiv svikt eller mindre svårigheter än så. De innehåller även färre propositioner,verb, långa ord, T-enheter, ord per T-enhet, har en kortare meningslängd samt har i snitt ettlägre LIX-värde. En logistisk regressionsanalys visade att demens (kontra minnesutredningarmed subjektiva besvär) predicerades signifikant (p < 0.01) av antalet verb samt av LIXvärdet.Totalt 85 % av fallen klassificerades korrekt.</p> / <p>Writing is a biomechanically complex process which demands a certain level of motor aswell as cognitive ability. Research concerning Alzheimer’s disease shows that impairmentsin multiple cognitive domains are notable before a clinical diagnosis can be made. There isalso research which indicates that written language ability in early life predicts the risk ofdementia in old age. The purpose of this study was to analyze whether measures derivedfrom narrative writing could predict dementia cross-sectionally. The material was 141 writtenpicture descriptions collected during routine investigations of cognitive disorders at theMemory Clinic, Karolinska University Hospital, Stockholm. The participants were classifiedinto three groups based on their diagnosis (subjective memory complaints, mild cognitiveimpairment and dementia). This study was based essentially on the four text measures: ideadensity, verb density, index of readability (LIX) and T-unit. As most of the texts were writtenby participants with some degree of cognitive decline the measures had to be modified tosome extent and detailed scoring protocols were worked out. The results indicate that writtenpicture descriptions made by individuals with dementia contained fewer words than thosewritten by individuals diagnosed with mild cognitive impairment or subjective cognitivecomplaints. They also contained fewer propositions, verbs, long words, T-units, words per Tunit,had a shorter mean sentence length and had a lower average LIX-value. A logisticregression analysis showed that cases of dementia, as opposed to subjective cognitivecomplaints, were significally predicted (p < 0.01) by the number of verbs and also by theLIX-value. Overall, 85 % of the cases were correctly classified.</p>

Skrivning är en biomekaniskt invecklad process som kräver en viss nivå av såväl motorisksom kognitiv förmåga. Forskning om Alzheimers sjukdom tyder på att nedsättningar i flerakognitiva domäner förekommer innan den kliniska diagnosen ställs. Det finns även forskningsom tyder på att ett innehållsrikt skriftspråk i unga år minskar risken för demensutveckling påäldre dagar. För att studera om mått från texter kunde predicera demens på ett tidigt stadiumanalyserades 141 skriftliga bildbeskrivningar insamlade inom ramen för rutinmässigaminnesutredningar vid Karolinska universitetssjukhuset, Huddinge. Deltagarna delades in itre grupper utifrån diagnos (minnesutredning, lindrig kognitiv svikt och demens).Utgångspunkt för studien var de fyra textmåtten: idétäthet, verbtäthet, läsbarhetsindex (LIX)och T-enheter. Då texterna i de flesta fall var skrivna av personer med kognitiv nedsättninghar måtten varit tvungna att modifieras och särskilda instruktioner för bedömning av texternahar utformats. Resultaten tyder på att skriftliga bildbeskrivningar utförda av individer meddemens innehåller färre totalt antal ord än de skrivna av individer diagnostiserade medlindrig kognitiv svikt eller mindre svårigheter än så. De innehåller även färre propositioner,verb, långa ord, T-enheter, ord per T-enhet, har en kortare meningslängd samt har i snitt ettlägre LIX-värde. En logistisk regressionsanalys visade att demens (kontra minnesutredningarmed subjektiva besvär) predicerades signifikant (p &lt; 0.01) av antalet verb samt av LIXvärdet.Totalt 85 % av fallen klassificerades korrekt. / Writing is a biomechanically complex process which demands a certain level of motor aswell as cognitive ability. Research concerning Alzheimer’s disease shows that impairmentsin multiple cognitive domains are notable before a clinical diagnosis can be made. There isalso research which indicates that written language ability in early life predicts the risk ofdementia in old age. The purpose of this study was to analyze whether measures derivedfrom narrative writing could predict dementia cross-sectionally. The material was 141 writtenpicture descriptions collected during routine investigations of cognitive disorders at theMemory Clinic, Karolinska University Hospital, Stockholm. The participants were classifiedinto three groups based on their diagnosis (subjective memory complaints, mild cognitiveimpairment and dementia). This study was based essentially on the four text measures: ideadensity, verb density, index of readability (LIX) and T-unit. As most of the texts were writtenby participants with some degree of cognitive decline the measures had to be modified tosome extent and detailed scoring protocols were worked out. The results indicate that writtenpicture descriptions made by individuals with dementia contained fewer words than thosewritten by individuals diagnosed with mild cognitive impairment or subjective cognitivecomplaints. They also contained fewer propositions, verbs, long words, T-units, words per Tunit,had a shorter mean sentence length and had a lower average LIX-value. A logisticregression analysis showed that cases of dementia, as opposed to subjective cognitivecomplaints, were significally predicted (p &lt; 0.01) by the number of verbs and also by theLIX-value. Overall, 85 % of the cases were correctly classified.

The aim of the present thesis was twofold, first to map the semantic memory decline in Alzheimer patients over time, second to take the patient’s perspective and create a multifaceted picture of the individual with Alzheimer’s disease through the study of memory, awareness, central coherence and emotions. Further issues concerned how Alzheimer individuals handled their cognitive erosion in everyday life and if they were well calibrated with their spouse in disease related matters. Two studies were performed, the first involved a longitudinal study of sematic deterioration, the second had a mixed methods design involving both quantitative and qualitative measures as in neuropsychological assessment and interviews. Through the longitudinal study it could be concluded that the nature of semantic deterioration is best described as loss of memory information rather than problems in accessing the information. It was further concluded that semantic concepts gradually lose their specific features during course of illness. The results from the second study revealed that the Alzheimer individuals were aware of their disease although they could not foresee the implications of their cognitive shortcomings in their everyday life. They evidenced weak central coherence, in that they were unable to infer details into a meaningful whole. This implies that they perceive their surrounding world in a fragmented way as consisting of separate objects rather than a comprehensible context. Concerning emotions it was found that they responded to negatively valenced words in the same way as normal ageing individuals, although being impaired in their response to positively and neutral words. Finally, the Alzheimer individuals and their spouses were not well calibrated regarding disease related issues. The findings of the present thesis have important clinical implications and gives valuable input to the understanding of the individual with Alzheimer’s disease. / Föreliggande avhandling hade två huvudsyften; dels att kartlägga försämringen av semantiskt minne hos Alzheimerpatienter över tid; dels att ta patientens perspektiv och skapa en mångfacetterad bild av individen med Alzheimers sjukdom. Fyra begrepp studerades i relation till detta, nämligen minne, medvetande, central koherens och emotioner. Ytterligare aspekter som studerades var hur Alzheimerindivider hanterar sina kognitiva tillkortakommanden i sin vardag samt hur väl kalibrerade de är med sin make/maka angående sjukdomsrelaterade frågor. Två studier genomfördes varav den första var en longitudinell studie av semantisk minnesförsämring och den andra hade en ’mixed methods’ design, inkluderande både kvantitativa (neuropsykologiska tester) och kvalitativa (intervjuer) metoder. Resultaten från den longitudinella studien avslöjade att semantiska begrepp som inte längre är välrepresenterade hos individen har gått förlorade snarare än att det skulle vara från om att individerna inte kan plocka fram informationen. Vidare kunde konstateras att semantiska begrepp gradvis tappar sina nyanser i takt med att sjukdomen fortskrider. Den andra studien visade att Alzheimerindividerna var medvetna om sin sjukdom och sina minnesproblem men att de inte kunde förutsäga vilka problem deras kognitiva tillkortakommanden skapade i deras vardag. De konstaterades ha svag central koherens vilket innebär att de ser sin omgivning på ett fragmentariskt sätt utan att kunna få ihop de olika objekten runt omkring sig till en meningsfull kontext. Vad gäller emotioner så kunde konstateras att Alzheimerindivider reagerar likadant som normalt åldrande individer på negativt laddade ord men att de är signifikant försämrade i förmågan att känna igen positiva och neutrala ord. Alzheimerindividerna och deras make/maka var inte väl kalibrerade vad gäller sjukdomsrelaterade frågor. Avhandlingens resultat har viktiga kliniska implikationer och ger ett värdefullt bidrag till förståelsen av en individ med Alzheimers sjukdom.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

INTRODUÇÃO: O Teste Breve de Performance Cognitiva (Syndrom Kurztest, SKT) (Erzigkeit, 2001) é um instrumento de rastreio cognitivo capaz de detectar déficits que caracterizam os estágios iniciais de demência ao avaliar as funções mnésticas e atencionais, com base na velocidade de processamento das informações. Pode ser usado em pacientes acamados. O escore total fornece dados quanto à severidade da doença. Resultados também podem ser avaliados quanto aos domínios de memória e atenção, permitindo que se dimensione a homogeneidade ou discrepância destes. OBJETIVOS: Este estudo tem como objetivos validar a versão brasileira do SKT e analisar suas propriedades diagnósticas em uma amostra clínica brasileira de sujeitos idosos com comprometimento cognitivo. MÉTODOS: Duzentos e sete sujeitos foram avaliados. O diagnóstico de consenso foi estabelecido por equipe multidisciplinar especializada, com base em dados clínicos, neuropsicológicos e de neuroimagem. A amostra foi composta por 45 pacientes com doença de Alzheimer (DA); 82 com Comprometimento Cognitivo Leve (CCL), e 80 controles normais (CN). Os dados foram avaliados considerando-se dois níveis educacionais ( 8 anos ou > 8 anos de estudo). RESULTADOS: As versões A e B do teste apresentaram alta consistência interna (Alfa de Cronbach =0,83 e 0,86, respectivamente), fidedignidade interavaliadores (p<0,001) e concordância entre suas duas versões (p<0,001). Os escores do SKT apontam para forte correlação com o Mini Exame do Estado Mental (MEEM) (r=-0,66; p<0,001) e com o Teste do Desenho do Relógio (TDR) (r=-0,57; p<0,001). Análise das curvas ROC indicou que o SKT é capaz de discrimina, para ambos os níveis educacionais, DA de CCL e CN, porém perde sua acurácia para discriminar CCL de CN. O SKT sofre leve influência da escolaridade. CONCLUSÕES: O SKT mantém as propriedades psicométricas originais e aponta para correlação significativa entre o MEEM, TDR e diagnóstico de consenso. Os achados sugerem que o teste é um adequado instrumento de rastreio para diferenciar a conversão de CCL para DA. É levemente influenciado pela escolaridade e pode não discriminar adequadamente sujeitos CCL de CN / BACKGROUND: The Short Cognitive Performance Test (Syndrom Kurztest, SKT) (Erzigkeit, 2001) is a bedside cognitive screening test capable of detecting deficits that characterize the early stages of dementia, as it evaluates memory and attention skills, taking into account the speed of information processing. The total score provides information about the severity of the disease. Results can also be interpreted in terms of attention and memory sub-scores to evaluate the homogeneity or discrepancy of deficits in these two domains. OBJECTIVES: The aim of this study is to validate the Brazilian version of the SKT, and to examine its diagnostic properties in a clinical sample of elderly individuals with cognitive impairment. METHODS: Two hundred and seven subjects were assessed. Consensus diagnoses were established by an expert multidisciplinary team, considering clinical, neuropsychological and neuroimaging data. The sample was characterized in 45 patients with Alzheimers disease (AD); 82 with mild cognitive impairment (MCI), and 80 normal controls (NC). These data were provided for two educational levels (low: 8 years; or high: > 8 years). RESULTS: Versions A and B of the test display high internal consistency (Cronbachs =.83 and .86, respectively), good inter-rater reliability (p<.001), and concordance between the two versions (p<.001). SKT scores correlate with the Mini-mental State Examination (MMSE) (r=-.66; p<.001) and the Clock Drawing Test (CDT) (r=-.57; p<.001). In both education strata, ROC analyses suggested that the SKT adequately discriminates AD from MCI and CN, but is less accurate to discriminate MCI from CN. The SKT suffers mild education bias. CONCLUSIONS: The SKT maintains its original psychometric properties and display significant correlation with the MMSE, CDT, and the consensus diagnosis. These findings suggest that the SKT is a good screening instrument to differentiate the transitional progress of MCI to AD. It is subject to mild educational bias, and may not adequately separate CN from patients with MCI

Introdução: O objetivo do estudo foi analisar a relação entre funções executivas e funcionalidade em uma amostra de idosos com diferentes graus de comprometimento cognitivo e caracterizar sua funcionalidade. O segundo objetivo deste estudo foi traduzir e adaptar culturalmente o instrumento Direct Assessment of Functional Status- revised (DAFS-R) para língua portuguesa (Brasil), avaliar as propriedades psicométricas do instrumento e caracterizar o perfil funcional de cada grupo diagnóstico. Estudos anteriores mostraram diferentes resultados entre avaliação objetiva e avaliação baseada em relatos de informantes sobre funcionalidade de um indivíduo. Neste estudo, foi comparada a avaliação funcional realizada através de medidas objetivas (teste de desempenho) e de julgamentos subjetivos (relatados por cuidadores). Métodos: 89 idosos (idade média de 73,8 anos) foram submetidos a avaliações clínica e neuropsicológica, e foram alocados em três grupos diagnósticos de acordo com nível cognitivo: controles (CO, n = 32), comprometimento cognitivo leve (CCL, n = 31) e doença de Alzheimer (DA, n = 26). As funções executivas foram avaliadas com o instrumento Executive Interview (EXIT25) e a funcionalidade foi medida objetivamente através da DAFS-BR. Resultados: Foi encontrada forte correlação negativa entre os escores da DAFS-BR e os escores da EXIT25 (r=- 0,872, p<0,001). A análise de regressão linear sugeriu uma influência significativa da EXIT-25 e do CAMCOG nos resultados da DAFS-BR. Médias significativamente diferentes foram observadas nos três diagnósticos em relação ao escore total da DAFS-BR. Os subdomínios da DAFS-BR capazes de diferenciar pacientes com CCL dos controles estavam relacionados às habilidades para lidar com dinheiro e de fazer compras. A adaptação transcultural mostrou boa consistência interna (alfa de Cronbach = 0,78), alta confiabilidade interavaliadores (0,996, p<0,001), bem como estabilidade teste-reteste ao longo do tempo (0,995, p <0,001). Correlação entre o escore total da DAFS-BR e do IQCODE foi significativa (r=-0,65, p<0,001). DAFSBR foi capaz de discriminar os grupos estudados (CO, CCL e DA). Análise da curva ROC sugeriu que DAFS-BR tem boa sensibilidade e especificidade para identificar com precisão pacientes com CCL, CO e DA. Conclusões: disfunção executiva está associada a pior capacidade de realizar atividades instrumentais da vida diária. Nesta amostra, os pacientes com CCL apresentaram pior estado funcional quando comparados aos controles. Pacientes com CCL podem apresentar alterações sutis no estado funcional, que somente são capturadas por medidas objetivas da funcionalidade. Resultados da adaptação transcultural e da avaliação das propriedades psicométricas sugerem que a DAFS-BR pode documentar diferentes graus de alterações do comprometimento funcional entre idosos brasileiros. Diagnósticos e tratamentos devem considerar estas diferenças entre métodos de avaliação funcional em vez de focar exclusivamente em relatos subjetivos de funcionalidade do paciente / Introduction: The objective of the study is to examine the association between executive functions and functional status in a cross section of older adults with varying degrees of cognitive impairment and characterize the functional status. The second objective of this study was to translate, culturally adapt the Direct Assessment of Functional Status- revised (DAFS-R) for Brazilian Portuguese (DAFS-BR), and to evaluate its reliability and validity to characterize the functional status in each diagnostic group. Previous studies show different results from objective assessment of functional abilities compared to information based on informants reports. In this study we compared perception of functional status between objective (performance test) e subjective (caregivers judgments) measures of assessment. Methods: 89 individuals (mean age 73.8 years) underwent clinical and neuropsychological evaluations, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n=32), mild cognitive impairment (MCI, n=31) and mild Alzheimers disease (AD, n=26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Brazilian version of the Direct Assessment of Functional Status test (DAFS-BR). Results: We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r=-0.872, p<0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. The results of cross-cultural adaptation, reliability and validity indicated good internal consistency (Cronbach´s alpha =0.78) in the total sample. DAFS-BR showed high inter-observer reliability (0.996; p<0.001) as well as test-retest stability over time (0.995; p<0.001). Correlation between the DAFS-BR total score and the IQCODE was moderate and significant (r=-0.65, p<0.001). Significantly different total DAFS-R scores were observed across the three diagnostic groups. The instrument was able to discriminate the studied groups (NC, MCI and AD). ROC curve analyses suggested that DAFS-BR has good sensitivity and specificity to identify MCI and DA from unimpaired controls. Conclusions: Executive dysfunction is associated with worse ability to undertake instrumental activities of the daily living. In this sample, patients with MCI showed worse functional status when compared to NC. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs. Results of cross-cultural adaptation, reliability and validity suggest DAFS-BR can document degrees of severity of functional impairment among Brazilian older adults. Diagnose and treatments should consider these discrepancies rather than focusing on subjective reports of patient functionality