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Authors
Abstract(s)
Enquadramento: Suspected Non-Alzheimer Disease Pathophysiology (SNAP) é um
conceito que surgiu recentemente, em 2012, categorizando um grupo de indivíduos que não
se enquadrava nos critérios histopatológicos definidores da doença de Alzheimer, aquando
da aplicação dos critérios da National Institute on Aging and Alzheimer’s Association.
SNAP é definida como uma condição neurológica identificável, in vivo, por
níveis normais do biomarcador amiloide-ß no cérebro. Contudo pela presença de um
depósito anormalmente elevado de proteína Tau, que se traduz em achados imagiológicos
de neurodegeneração, isto é, atrofia cerebral identificável por técnicas de imagem. Estimase que esteja presente em aproximadamente 23% dos indivíduos cognitivamente normais
com idade superior a 70 anos e em cerca de 25% dos indivíduos com comprometimento
cognitivo moderado. Resultados de estudos recentes mostram-se muito dispares no que
concerne aos outcomes cognitivos, quando os indivíduos SNAP são comparados a
indivíduos sem neurodegeneração e com níveis normais de amiloide-ß. Assim, prende-se a
ansia de compreender o impacto cognitivo desta condição, assim como potenciais fatores
de risco da mesma.
Objetivos: Caracterizar demograficamente e cognitivamente uma população de indivíduos
SNAP em comparação com doentes sem demência estabelecida e doentes com doença de
Alzheimer.
Materiais e métodos: Análise transversal, descritiva e comparativa de uma amostra de
1682 indivíduos. Os dados usados na preparação desta dissertação, arquivo de dados
UPENNBIOMK_MASTER.csv, foram transferidos do banco de dados da Alzheimer’s
Disease Neuroimaging Initiative (ADNI), após prévia exposição e argumentação das
intenções do estudo. Os dados incluídos foram recolhidos das coortes da ADNI 1 (iniciada
em 2004 e duração de 5 anos), ADNI GO (iniciada em 2009 e duração de 2 anos) e ADNI 2
(iniciada em 2011 e duração de 5 anos). A seleção do período temporal da pesquisa é
coincidente com as datas de início e de termino de tais projetos. Os indivíduos foram
classificados como controlos quando apresentavam níveis de amiloide-ß e Tau normais no
liquido cefalorraquidiano, como potencialmente com doença de Alzheimer quando ambos
os doseamentos eram anormais e, como SNAP quando apresentavam níveis elevados de tau
com doseamento de amiloide-ß normal. Os grupos foram caracterizados cognitivamente de
acordo com as variáveis disponíveis na base de dados referida.
Resultados: Da análise de 1682 participantes incluídos neste estudo, 295 são SNAP. A
percentagem de indivíduos do sexo masculino é 50.9%, com uma idade média de 71.99 ± 8.09 anos. Relativamente aos anos de educação, o grupo SNAP apresenta uma média de
anos de escolaridade de 16.47 ± 2.61 anos. A positividade ao gene ApoE4 presente nesta
população é de 19.66%. Os níveis médios dos biomarcadores no líquido cefalorraquidiano
quantificados foram os seguintes: [Aß] = 236.21 ± 27.13 pg/ml, [Tau total] = 72.57 ± 31.05
pg/ml e [Tau fosforilada] =33.91 ± 10.44 pg/ml. Relativamente ao nível de performance
cognitiva, globalmente o grupo SNAP obteve pontuações semelhantes ao grupo controlo e
reiteradamente superiores às obtidas pelos indivíduos com Doença de Alzheimer. O grupo
SNAP obteve resultados significativamente superiores ao controlo normal nas seguintes
provas: o Teste de Memória Imediata e o Teste de Memória de Longo Prazo, que avaliam,
respetivamente, a capacidade de reter uma quantidade limitada de informação durante um
curto período de tempo (segundos, minutos a horas) e a capacidade de memorizar uma
quantidade virtualmente infinita de informação durante um tempo indefinido.
Conclusão: Foi constatado de forma transversal a todos os exames cognitivos aplicados
neste estudo, que a condição neurológica SNAP se traduz numa performance cognitiva
significativamente melhor que a de doentes com doença de Alzheimer, sugerindo o carácter
menos severo desta entidade. Este estudo permitirá explorar a correlação cognitiva com
parâmetros neuroimagiológicos destas populações, com o objetivo de identificação precoce
destes doentes e respetiva evolução clinica.
Background: Suspected Non-Alzheimer Disease Pathophysiology (SNAP) is a concept that emerged recently, in 2012, categorizing a group of individuals who did not fit the histopathological criteria defining Alzheimer's disease, when applying the criteria of the National Institute on Aging and Alzheimer's Association. SNAP is defined as a neurological condition characterized, in vivo, by normal levels of the biomarker amyloid-ß in the brain. However, it features an abnormally high deposit of Tau protein, which translates into imaging findings of neurodegeneration, that is, brain atrophy identifiable by imaging techniques. It is estimated to be present in approximately 23% of cognitively normal individuals over the age of 70 years and in approximately 25% of individuals with moderate cognitive impairment. Results from recent studies are very different in terms of cognitive outcomes when SNAP individuals are compared to individuals without neurodegeneration and with normal levels of amyloid-ß. Thus, there is a need to understand the cognitive impact of this condition, as well as its potential risk factors. Aims: Characterize demographically and cognitively a population of SNAP individuals compared to patients without established dementia and patients with Alzheimer's disease. Materials and methods: Cross-sectional, descriptive, and comparative analysis of a sample of 1682 individuals. The data used in the preparation of this dissertation, the UPENNBIOMK_MASTER.csv data file, was transferred from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, after prior exposure and argumentation of the study intent. Data included were collected from ADNI 1 (initiated in 2004 and duration of 5 years), ADNI GO (initiated in 2009 and duration of 2 years), and ADNI 2 (initiated in 2011 and duration of 5 years) cohorts. The selection of the period time for the research matches with the start and end dates of such projects. Subjects were classified as controls when they had normal cerebrospinal fluid amyloid-ß and Tau levels, as potentially with Alzheimer's disease when both assays were abnormal; as SNAP when they had high levels of tau with the normal amyloid-ß assay. The groups were cognitively characterized according to the variables available in the aforementioned database. Results: From the analysis of 1682 participants included in this study, 295 are SNAP. The percentage of males is 50.9%, with a mean age of 71.99 ± 8.09 years. Regarding years of education, the SNAP group has an average number of years of schooling of 16.47 ± 2.61 years. The positivity to the ApoE4 gene present in this population is 19.66%. Mean of cerebrospinal fluid biomarker levels quantified were as follows: [Aß] = 236.21 ± 27.13 pg/ml, [Total Tau] = 72.57 ± 31.05 pg/ml and [phosphorylated Tau] =33.91 ± 10.44 pg/ml. Regarding the level of cognitive performance, overall the SNAP group obtained scores similar to the control group and repeatedly higher than those obtained by individuals with Alzheimer's Disease. The SNAP group obtained significantly better results than the normal control in the following tests: the Immediate Memory Test and in the Long-Term Memory Test, which assess, respectively, the ability to retain a limited amount of information over a short period of time (seconds, minutes to hours) and the ability to memorize a virtually infinite amount of information over an indefinite amount of time. Conclusion: It was found across all cognitive tests applied in this study that the neurological condition SNAP translates into a significantly better cognitive performance than the observed in Alzheimer's disease patients, suggesting the less severe nature of this entity. This study will explore the cognitive correlation with neuroimaging parameters of these populations, with the aim of early identification of these patients and their respective clinical evolution.
Background: Suspected Non-Alzheimer Disease Pathophysiology (SNAP) is a concept that emerged recently, in 2012, categorizing a group of individuals who did not fit the histopathological criteria defining Alzheimer's disease, when applying the criteria of the National Institute on Aging and Alzheimer's Association. SNAP is defined as a neurological condition characterized, in vivo, by normal levels of the biomarker amyloid-ß in the brain. However, it features an abnormally high deposit of Tau protein, which translates into imaging findings of neurodegeneration, that is, brain atrophy identifiable by imaging techniques. It is estimated to be present in approximately 23% of cognitively normal individuals over the age of 70 years and in approximately 25% of individuals with moderate cognitive impairment. Results from recent studies are very different in terms of cognitive outcomes when SNAP individuals are compared to individuals without neurodegeneration and with normal levels of amyloid-ß. Thus, there is a need to understand the cognitive impact of this condition, as well as its potential risk factors. Aims: Characterize demographically and cognitively a population of SNAP individuals compared to patients without established dementia and patients with Alzheimer's disease. Materials and methods: Cross-sectional, descriptive, and comparative analysis of a sample of 1682 individuals. The data used in the preparation of this dissertation, the UPENNBIOMK_MASTER.csv data file, was transferred from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, after prior exposure and argumentation of the study intent. Data included were collected from ADNI 1 (initiated in 2004 and duration of 5 years), ADNI GO (initiated in 2009 and duration of 2 years), and ADNI 2 (initiated in 2011 and duration of 5 years) cohorts. The selection of the period time for the research matches with the start and end dates of such projects. Subjects were classified as controls when they had normal cerebrospinal fluid amyloid-ß and Tau levels, as potentially with Alzheimer's disease when both assays were abnormal; as SNAP when they had high levels of tau with the normal amyloid-ß assay. The groups were cognitively characterized according to the variables available in the aforementioned database. Results: From the analysis of 1682 participants included in this study, 295 are SNAP. The percentage of males is 50.9%, with a mean age of 71.99 ± 8.09 years. Regarding years of education, the SNAP group has an average number of years of schooling of 16.47 ± 2.61 years. The positivity to the ApoE4 gene present in this population is 19.66%. Mean of cerebrospinal fluid biomarker levels quantified were as follows: [Aß] = 236.21 ± 27.13 pg/ml, [Total Tau] = 72.57 ± 31.05 pg/ml and [phosphorylated Tau] =33.91 ± 10.44 pg/ml. Regarding the level of cognitive performance, overall the SNAP group obtained scores similar to the control group and repeatedly higher than those obtained by individuals with Alzheimer's Disease. The SNAP group obtained significantly better results than the normal control in the following tests: the Immediate Memory Test and in the Long-Term Memory Test, which assess, respectively, the ability to retain a limited amount of information over a short period of time (seconds, minutes to hours) and the ability to memorize a virtually infinite amount of information over an indefinite amount of time. Conclusion: It was found across all cognitive tests applied in this study that the neurological condition SNAP translates into a significantly better cognitive performance than the observed in Alzheimer's disease patients, suggesting the less severe nature of this entity. This study will explore the cognitive correlation with neuroimaging parameters of these populations, with the aim of early identification of these patients and their respective clinical evolution.
Description
Keywords
Cognição Doença de Alzheimer Neurodegeneração Suspected Non-Alzheimer'S Disease Pathophysiology