RESUMEN
BACKGROUND: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. OBJECTIVE: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. METHODS: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. RESULTS: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognitionâ+âCS), and bvFTD versus AD (71.7%, social cognitionâ+âCS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. CONCLUSION: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.
Asunto(s)
Enfermedad de Alzheimer , Demencia Frontotemporal , Tamizaje Masivo , Enfermedad de Parkinson , Cognición Social , Anciano , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , Atrofia/patología , Encéfalo/patología , Encéfalo/fisiopatología , Función Ejecutiva , Femenino , Demencia Frontotemporal/clasificación , Demencia Frontotemporal/patología , Sustancia Gris/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia/estadística & datos numéricos , Persona de Mediana Edad , Enfermedades Neurodegenerativas/diagnóstico , Enfermedad de Parkinson/clasificación , Enfermedad de Parkinson/patología , América del SurRESUMEN
The 3D tortuosity determined in several brain areas is proposed as a new morphological biomarker (BM) to be considered in early detection of Alzheimer's disease (AD). It is measured using the sum of angles method and it has proven to be sensitive to anatomical changes that appear in gray and white matter and temporal and parietal lobes during mild cognitive impairment (MCI). Statistical analysis showed significant differences (p < 0.05) between tortuosity indices determined for healthy controls (HC) vs. MCI and HC vs. AD in most of the analyzed structures. Other clinically used BMs have also been incorporated in the analysis: beta-amyloid and tau protein CSF and plasma concentrations, as well as other image-extracted parameters. A classification strategy using random forest (RF) algorithms was implemented to discriminate between three samples of the studied populations, selected from the ADNI database. Classification rates considering only image-extracted parameters show an increase of 9.17%, when tortuosity is incorporated. An enhancement of 1.67% is obtained when BMs measured from several modalities are combined with tortuosity.
Asunto(s)
Algoritmos , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Anciano , Enfermedad de Alzheimer/patología , Encéfalo/patología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
The Brazilian Civil Code, which came into force in 2002, established a functional criterion for guardianship proceedings and introduced the concept of "limited guardianship," applied to cases in which incapacity to exercise civil rights is partial. With population aging and the growth in the number of older people with cognitive impairments, such as Alzheimer's disease (AD), the need to invoke legal remedies against elder abuse increased; however, difficulties in assessing capacity still lead to a majority of decisions in favor of plenary guardianship. The present article compiled data on capacity in AD subjects. The varying degrees of decision-making impairment at different stages of AD might be compatible with limited guardianship in milder cases of the disease.
Asunto(s)
Enfermedad de Alzheimer/psicología , Tutores Legales/legislación & jurisprudencia , Enfermedad de Alzheimer/clasificación , Brasil , Derechos Civiles/legislación & jurisprudencia , Toma de Decisiones , Humanos , Competencia Mental/legislación & jurisprudenciaRESUMEN
The Brazilian Civil Code, which came into force in 2002, established a functional criterion for guardianship proceedings and introduced the concept of “limited guardianship,” applied to cases in which incapacity to exercise civil rights is partial. With population aging and the growth in the number of older people with cognitive impairments, such as Alzheimer’s disease (AD), the need to invoke legal remedies against elder abuse increased; however, difficulties in assessing capacity still lead to a majority of decisions in favor of plenary guardianship. The present article compiled data on capacity in AD subjects. The varying degrees of decision-making impairment at different stages of AD might be compatible with limited guardianship in milder cases of the disease.
Asunto(s)
Humanos , Enfermedad de Alzheimer/psicología , Tutores Legales/legislación & jurisprudencia , Brasil , Derechos Civiles/legislación & jurisprudencia , Competencia Mental/legislación & jurisprudencia , Toma de Decisiones , Enfermedad de Alzheimer/clasificaciónRESUMEN
BACKGROUND: Neuroimaging techniques combined with computational neuroanatomy have been playing a role in the investigation of healthy aging and Alzheimer's disease (AD). The definition of normative rules for brain features is a crucial step to establish typical and atypical aging trajectories. OBJECTIVE: To introduce an unsupervised pattern recognition method; to define multivariate normative rules of neuroanatomical measures; and to propose a brain abnormality index. METHODS: This study was based on a machine learning approach (one class classification or novelty detection) to neuroanatomical measures (brain regions, volume, and cortical thickness) extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s database. We applied a ν-One-Class Support Vector Machine (ν-OC-SVM) trained with data from healthy subjects to build an abnormality index, which was compared with subjects diagnosed with mild cognitive impairment and AD. RESULTS: The method was able to classify AD subjects as outliers with an accuracy of 84.3% at a false alarm rate of 32.5%. The proposed brain abnormality index was found to be significantly associated with group diagnosis, clinical data, biomarkers, and future conversion to AD. CONCLUSION: These results suggest that one-class classification may be a promising approach to help in the detection of disease conditions. Our findings support a framework considering the continuum of brain abnormalities from healthy aging to AD, which is correlated with cognitive impairment and biomarkers measurements.
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Envejecimiento/patología , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Máquina de Vectores de Soporte , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , Disfunción Cognitiva/clasificación , Disfunción Cognitiva/patología , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tamaño de los Órganos , Reconocimiento de Normas Patrones Automatizadas/métodos , Sensibilidad y Especificidad , Aprendizaje Automático no SupervisadoRESUMEN
Preclinical diagnosis of Alzheimer's disease using biomarkers has become an area of great interest for both clinicians and researchers because, among other advantages, this would increase the response to new disease-modifying drugs. However, difficulties with compliance and economic costs marginalize many countries worldwide that do not have access to this new type of diagnosis. The opportunity exists to refine the conventional clinical method, without using biomarkers, to attempt an earlier diagnosis as there is information that supports the potential utility of a focused clinical interview, observation of gait and use of more demanding memory tests.
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Enfermedad de Alzheimer/diagnóstico , Diagnóstico Precoz , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/economía , Biomarcadores/análisis , Cognición , Marcha , Humanos , Entrevistas como Asunto , Memoria , Examen Neurológico , Pruebas NeuropsicológicasRESUMEN
Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. This review highlights the role of genetics in understanding the pieces of the complex AD puzzle and summarizes the genes known to be involved in Alzheimer's disease. The amount of risk of Alzheimer's disease that is attributable to genetics is estimated to be â¼70%. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. Although mutations in these genes account for â¼1% of AD cases, their identification has been crucial to understand the molecular mechanisms of AD. For the more common complex late-onset AD, the É-4 allele of the gene encoding apolipoprotein E (APOE) has been recognized as a major genetic risk factor. More recently, several potential disease risk genes have been identified with the use of advanced genomic methods like genome-wide association studies (GWAS). In the end, the knowledge of the pathophysiological mechanisms leading to AD will enable the development of more accurate diagnostic tests and new disease-treating strategies.
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/clasificación , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/genética , Predisposición Genética a la Enfermedad , Humanos , Mutación/genética , Presenilina-1/genética , Presenilina-2/genéticaRESUMEN
OBJECTIVE: To evaluate the contribution of quantitative electroencephalographic (qEEG) analyses in the diagnosis of Alzheimer's disease (AD). METHOD: Thirty-five patients from the Neurology Outpatients Clinic of PUC-Campinas, diagnosed with AD according to the NINCDS/ADRDA were evaluated, and compared with a control group consisting of 30 individuals with no cognitive deficit. The procedures consisted of clinical-neurological, cognitive and behavioral analyses and the qEEG (absolute power and coherence). RESULTS: The AD group presented greater absolute power values in the delta and theta bands, greater theta/alpha indices and less frontal alpha and beta coherence. Logistic multiple regression models were constructed and those only showing variations in the qEEG (frontal alpha coherence and left frontal absolute theta power) showed an accuracy classification (72.3%) below that obtained in the mini-mental state examination (93%). CONCLUSION: The study of coherence and power in the qEEG showed a relatively limited accuracy with respect to its application in routine clinical practice.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Electroencefalografía/métodos , Anciano , Enfermedad de Alzheimer/clasificación , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the contribution of quantitative electroencephalographic (qEEG) analyses in the diagnosis of Alzheimer's disease (AD). METHOD: Thirty-five patients from the Neurology Outpatients Clinic of PUC-Campinas, diagnosed with AD according to the NINCDS/ADRDA were evaluated, and compared with a control group consisting of 30 individuals with no cognitive deficit. The procedures consisted of clinical-neurological, cognitive and behavioral analyses and the qEEG (absolute power and coherence). RESULTS: The AD group presented greater absolute power values in the delta and theta bands, greater theta/alpha indices and less frontal alpha and beta coherence. Logistic multiple regression models were constructed and those only showing variations in the qEEG (frontal alpha coherence and left frontal absolute theta power) showed an accuracy classification (72.3 percent) below that obtained in the mini-mental state examination (93 percent). CONCLUSION: The study of coherence and power in the qEEG showed a relatively limited accuracy with respect to its application in routine clinical practice.
OBJETIVO: Avaliar a contribuição das análises quantitativas do eletroencefalograma (qEEG) no diagnóstico da doença de Alzheimer (DA). MÉTODO: Foram avaliados 35 pacientes do ambulatório de Neurologia Clínica da PUC-Campinas, com o diagnóstico de DA segundo o NINCDS/ADRDA e comparados a 30 indivíduos, sem déficit cognitivo, de grupo controle. Os procedimentos foram avaliação clínico-neurológica, cognitiva e comportamental e EEGq (potência absoluta e coerência). RESULTADOS: O grupo DA apresentou maiores potências absolutas nas faixas delta e teta, maiores índices teta/alfa e menor coerência alfa e beta frontal. Foram construídos modelos de regressão múltipla logística e aquele que contou apenas com variáveis do EEGq (coerência alfa frontal e potência absoluta teta frontal esquerda) teve acurácia de classificação (72,3 por cento), inferior à obtida com o mini-exame do estado mental (93 por cento). CONCLUSÃO: O estudo de coerência e potência no qEEG tem acurácia relativamente limitada no sentido de aplicação prática clínica rotineira.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/diagnóstico , Electroencefalografía/métodos , Enfermedad de Alzheimer/clasificación , Estudios de Casos y Controles , Modelos Logísticos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: At least for a subset of patients, the clinical diagnosis of mild cognitive impairment (MCI) may represent an intermediate stage between normal aging and dementia. Nevertheless, the patterns of transition of cognitive states between normal cognitive aging and MCI to dementia are not well established. In this study we address the pattern of transitions between cognitive states in patients with MCI and healthy controls, prior to the conversion to dementia. METHODS: 139 subjects (78% women, mean age, 68.5 +/- 6.1 years; mean educational level, 11.7 +/- 5.4 years) were consecutively assessed in a memory clinic with a standardized clinical and neuropsychological protocol, and classified as cognitively healthy (normal controls) or with MCI (including subtypes) at baseline. These subjects underwent annual reassessments (mean duration of follow-up: 2.7 +/- 1.1 years), in which cognitive state was ascertained independently of prior diagnoses. The pattern of transitions of the cognitive state was determined by Markov chain analysis. RESULTS: The transitions from one cognitive state to another varied substantially between MCI subtypes. Single-domain MCI (amnestic and non-amnestic) more frequently returned to normal cognitive state upon follow-up (22.5% and 21%, respectively). Among subjects who progressed to Alzheimer's disease (AD), the most common diagnosis immediately prior conversion was multiple-domain MCI (85%). CONCLUSION: The clinical diagnosis of MCI and its subtypes yields groups of patients with heterogeneous patterns of transitions between one given cognitive state to another. The presence of more severe and widespread cognitive deficits, as indicated by the group of multiple-domain amnestic MCI may be a better predictor of AD than single-domain amnestic or non-amnestic deficits. These higher-risk individuals could probably be the best candidates for the development of preventive strategies and early treatment for the disease.
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Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Anciano , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/psicología , Trastornos del Conocimiento/clasificación , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , PsicometríaRESUMEN
Multispectral image analysis is a relatively promising field of research with applications in several areas, such as medical imaging and satellite monitoring. A considerable number of current methods of analysis are based on parametric statistics. Alternatively, some methods in computational intelligence are inspired by biology and other sciences. Here we claim that philosophy can be also considered as a source of inspiration. This work proposes the objective dialectical method (ODM): a method for classification based on the philosophy of praxis. ODM is instrumental in assembling evolvable mathematical tools to analyze multispectral images. In the case study described in this paper, multispectral images are composed of diffusion-weighted (DW) magnetic resonance (MR) images. The results are compared to ground-truth images produced by polynomial networks using a morphological similarity index. The classification results are used to improve the usual analysis of the apparent diffusion coefficient map. Such results proved that gray and white matter can be distinguished in DW-MR multispectral analysis and, consequently, DW-MR images can also be used to furnish anatomical information.
Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/métodos , Algoritmos , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , Encéfalo/anatomía & histología , Humanos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
OBJECTIVE: The objective of the study was the analysis of agreement between the CDR scale with diagnostic criteria and mini mental state examination (MMSE), as well as correlation with Blessed scale, in a sample of Southern Brazilian patients. METHOD: The CDR scale was cross-sectionally evaluated in 269 dementia patients' Alzheimer's disease (AD) vascular dementia, and questionable. The NINCDS-ADRDA criteria for probable AD and the NINDS-AIREN for probable vascular dementia were the gold standard. The MMSE, the Blessed scale, the Hachinski ischemic score, and a battery of cognitive tests were also applied. RESULTS: The agreement to gold standard was good (kappa=0.73), while to MMSE categorized was moderate (kappa=0.53). A significant correlation with the Blessed scale (r=0.96; p=0.001) was observed. Education and age were similar among CDR categories. CONCLUSION: The global score agreement of the CDR scale with the gold standard was good, and with the MMSE was moderate. We also observed face validity for dementia severity. No impact of education was observed upon CDR global scores.
Asunto(s)
Demencia/diagnóstico , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Anciano , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Brasil , Demencia/clasificación , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados , TraducciónRESUMEN
OBJETIVO: Avaliar a concordância da escala CDR com critérios diagnósticos e mini exame do estado mental (MEEM), e correlação com escala de Blessed, numa amostra de pacientes do sul do Brasil. MÉTODO: A escala foi avaliada em 269 pacientes com doença de Alzheimer (DA), demência vascular e demência questionável num desenho transversal. Os critérios do NINCDS-ADRDA para provável DA e NINDS-AIREN para provável demência vascular foram os padrões-ouro. O MEEM, a escala Blessed para gravidade da demência, o escore isquêmico de Hachinski, e uma bateria de testes cognitivos também foram aplicados. RESULTADOS: A concordância com o padrão-ouro foi boa (kappa=0,73), e com o MEEM em categorias foi moderada (kappa= 0,53). Observou-se correlação significativa da escala CDR com Blessed (r=0,96; p=0,001). Não se observou diferença de escolaridade ou de idade entre as categorias da escala CDR. CONCLUSÃO: A concordância da CDR foi boa para os critérios diagnósticos e moderada para o MEEM. A escala mostrou validade de construto para gravidade de demência. Não se observou impacto da escolaridade sobre este instrumento.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Demencia/diagnóstico , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Brasil , Demencia/clasificación , Psicometría , Reproducibilidad de los Resultados , TraducciónRESUMEN
The heterogeneity and variants of Alzheimer disease (AD) are reviewed. There are cases with a slow or fast evolution and with early or late onset. Most cases are sporadic but there are also hereditary forms. About 50% of patients show neuropsychiatric disorders (depression and psychoses). Some cases have a greater deficit of right or left hemispheric functions. Among the variants, there are forms that start as pure aphasias, predominantly prefrontal cases and posterior cortical forms. Occasionally AD may simulate other disorders such as supranuclear palsy, corticobasal ganglionar degeneration and Jacob-Creutzfeldt disease. Finally, there are mixed forms, in which AD is associated with cerebrovascular disease (very commonly) and with other diseases such as dementia with Lewy bodies. We conclude that AD is a heterogeneous disorder and, therefore, clinical diagnosis may be insufficient. Biological markers and specific imaging studies are needed for a correct clinical diagnosis.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , HumanosRESUMEN
The heterogeneity and variants of Alzheimer disease (AD) are reviewed. There are cases with a slow or fast evolution and with early or late onset. Most cases are sporadic but there are also hereditary forms. About 50 percent of patients show neuropsychiatric disorders (depression and psychoses). Some cases have a greater deficit of right or left hemispheric functions. Among the variants, there are forms that start as pure aphasias, predominantly prefrontal cases and posterior cortical forms. Occasionally AD may simulate other disorders such as supranuclear palsy, corticobasal ganglionar degeneration and Jacob-Creutzfeldt disease. Finally, there are mixed forms, in which AD is associated with cerebrovascular disease (very commonly) and with other diseases such as dementia with Lewy bodies. We conclude that AD is a heterogeneous disorder and, therefore, clinical diagnosis may be insufficient. Biological markers and specific imaging studies are needed for a correct clinical diagnosis.
Asunto(s)
Humanos , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patologíaRESUMEN
INTRODUCTION: Alzheimer's disease (AD) is a degenerative dementia that may disclose different cognitive, behavioral, psychiatric and functional symptoms since onset. These distinct cognitive profiles support the conception of clinical heterogeneity and account for AD's highly variable rate of progression. In spite of strict diagnostic criteria NINCS ADRDA's and DSM IV the clinical certainty is only about 85%. Mayeux define 4 subtypes: a). Benign: mild cognitive and functional impairment without focal signs and late onset behavioral signs, slow progression; b). Myoclonic: usually of presenile onset with severe cognitive deterioration, mutism and early onset myoclonus; c). Extrapyramidal: early onset akineto rigid signs with severe cognitive, behavioral and psychiatric involvement; d). Typical: gradual and progressive cognitive, behavioral and functional impairment. The differentiation of these subtypes will allow us to define discrete patterns of progression, to define prognostic subgroups, and to homogenize them for clinical research and drug trials. DEVELOPMENT: We examined 1000 charts of probable AD patients from the Santojanni Center. We found 42% extrapyramidal, 35% typical, 15% benign and 8% myoclonic. The early onset of parkinsonism and myoclonus predict a rapidly evolving cognitive impairment and a more severe rate of progression with psychiatric disorders and dependency in activities of daily living. (DADL) Patients with low level of education, low cognitive performance at entry as well as those with rapid rate of cognitive deterioration had a faster rate of progression to DADL. CONCLUSION: Delusions, low level of education, extrapyramidal signs and motor hyperactivity but not hallucinations, and anosognosia were the best non cognitive predictors of DADL.