Positive attributes in elderly people with different degrees of depression: a study based on network analysis.

INTRODUCTION: Depression in aging may lead to loss of autonomy and worsening of comorbidities. Understanding how positive attributes contribute to healthier and happier aging has been one of the purposes of Positive Psychology. However, the literature still lacks studies that evaluate how depression in the elderly is related to constructs considered positive. OBJECTIVE: The present study aimed comparing scores of constructs of spiritual well-being, social support, self-esteem, life satisfaction, affection, optimism, and hope in the elderly with minimal, mild, moderate, and severe depression and healthy controls in order to investigate possible indirect and mediated relationships between positive constructs and depression. METHODS: A cross-sectional study was conducted with elderly, 62 of whom were diagnosed with different severity of Major Depression (DSM-V) (minimum, mild, moderate, and severe according to the Beck Depression Inventory - BDI) and 66 healthy controls matched by age, sex and schooling. The instruments used were adapted and validated versions of the Spirituality Self-Rating Scale, the Rosenberg Self-Esteem Scale, the Medical Outcomes Social Scale of Support, the Life Satisfaction Scale, the Positive and Negative Affect Schedule, the Revised Life Orientation Test, and the Adult Dispositional Hope Scale. After comparing the means of scores between groups, an analysis of normalized partial association networks was performed to investigate the direct and mediated relationships between depression and other evaluated constructs. RESULTS: Scores of spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism, negative affects, and hope differed significantly between the control group and the degrees of depression (p < 0.001). The analysis of normalized partial association networks has shown that the relations of depression with the constructs of life satisfaction, self-esteem, and social support are mediated, while the constructs of dispositional hope, positive affect, spiritual well-being, and optimism are indirectly related to depression. The social class was also positively related to depression. CONCLUSION: Depression in different degrees is associated with a reduction in the scores of instruments that evaluate positive attributes. The constructs directly associated with depression are spiritual well-being, optimism, positive affect, and dispositional hope. The others had mediated relationship. These results may contribute to the planning of future interventions for the prevention of depression among the elderly.

Positive attributes in elderly people with different degrees of depression: a study based on network analysis

Abstract Introduction Depression in aging may lead to loss of autonomy and worsening of comorbidities. Understanding how positive attributes contribute to healthier and happier aging has been one ofthe purposes of Positive Psychology. However, the literature still lacks studies that evaluate how depression in the elderly is related to constructs considered positive. Objective The present study aimed comparing scores of constructs of spiritual well-being, social support, selfesteem, life satisfaction, affection, optimism, and hope in the elderly with minimal, mild, moderate, and severe depression and healthy controls in order to investigate possible indirect and mediated relationships between positive constructs and depression. Methods A cross-sectional study was conducted with elderly, 62 of whom were diagnosed with different severity of Major Depression (DSM-V) (minimum, mild, moderate, and severe according to the Beck Depression Inventory - BDI) and 66 healthy controls matched by age, sex and schooling. The instruments used were adapted and validated versions of the Spirituality Self-Rating Scale, the Rosenberg Self-Esteem Scale, the Medical Outcomes Social Scale of Support, the Life Satisfaction Scale, the Positive and Negative Affect Schedule, the Revised Life Orientation Test, and the Adult Dispositional Hope Scale. After comparing the means of scores between groups, an analysis of normalized partial association networks was performed to investigate the direct and mediated relationships between depression and other evaluated constructs. Results Scores of spiritual well-being, social support, self-esteem, life satisfaction, positive affect, optimism, negative affects, and hope differed significantly between the control group and the degrees of depression (p < 0.001). The analysis of normalized partial association networks has shown that the relations of depression with the constructs of life satisfaction, self-esteem, and social support are mediated, while the constructs of dispositional hope, positive affect, spiritual well-being, and optimism are indirectly related to depression. The social class was also positively related to depression. Conclusion Depression in different degrees is associated with a reduction in the scores of instruments that evaluate positive attributes. The constructs directly associated with depression are spiritual well-being, optimism, positive affect, and dispositional hope. The others had mediated relationship. These results may contribute to the planning of future interventions for the prevention of depression among the elderly.

Investigation of the Association Between History of Learning Disabilities and Primary Progressive Aphasia in Brazilian Portuguese Speakers.

Primary Progressive Aphasia (PPA) is a neurological syndrome characterized by impaired language due to neurodegeneration. It is subdivided into three variants: semantic, agrammatic or nonfluent, and logopenic. Pieces of evidence have suggested that learning disabilities in childhood, such as dyslexia, might be susceptibility factors in the occurrence of PPA in adulthood. The objective of this study was to verify the existence of the relationship between PPA and the history of learning disabilities of patients and their children, compared to a control group of individuals with Alzheimer's disease (AD). A questionnaire was applied to investigate the presence of indicators of learning disabilities and difficulties in individuals with PPA and AD and their children. Twenty subjects with PPA and 16 with AD participated in the study. Our findings are presented and discussed in light of the current scientific evidence and the social, educational, and economic Brazilian scenario. Despite the challenges of doing research with individuals with PPA in Brazil, we present the first evidence about the investigation of association between the history of learning disabilities and difficulties and PPA in native Brazilian Portuguese speakers.

First Symptoms of Primary Progressive Aphasia and Alzheimer's Disease in Brazilian Individuals.

Background: Primary Progressive Aphasia (PPA) is characterized by progressive language impairment due to focal degeneration of brain areas related to linguistic processing. The detection and differential diagnosis of PPA can be difficult with clinical features that may overlap with features of other neurological conditions, such as Alzheimer's disease (AD). The scientific production on PPA in Latin American patients is still scarce. This study investigated the first symptoms in a Brazilian sample of patients with PPA in comparison with AD patients. Method: We compared the first symptoms reported by caregivers of people with PPA (n = 20; semantic variant n = 8, non-fluent variant n = 7, logopenic variant n = 3, and unclassified cases n = 2) and AD (n = 16). Data were collected through the application of a structured questionnaire that was presented in an interview format to the caregiver who knew the patient best. Results: Anomia, paraphasias and motor speech difficulties were the first symptoms capable of differentiating patients with PPA from those with AD, while memory was exclusive of AD. Among the PPA variants, anomia was the initial symptom associated with the semantic variant, while motor speech difficulties were associated with the non-fluent variant. The results are discussed considering the unique cultural and sociodemographic characteristics of this studied population. Conclusion: This study demonstrated that some of the initial symptoms of PPA patients may be unique to clinical variants of PPA and of AD, and their investigation may be useful for the early and differential diagnosis of this population.

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil.

INTRODUCTION: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly). METHODS: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, α-synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. RESULTS: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). DISCUSSION: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

INTRODUÇÃO: Este trabalho visa avaliar alterações neurodegenerativas detectadas por depósitos proteicos anormais em Córtex Entorrinal (CE) de indivíduos acima de 50 anos e correlacionar os achados com suspeição de demência detectada por meio do IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly). MÉTODOS: Catorze encéfalos foram submetidos à técnica imuno-histoquímica para diferentes proteínas (beta-amiloide, tau, alfa-sinucleína e fosfo-TDP-43) e esses dados foram comparados com os valores obtidos pelo IQCODE. RESULTADOS: 57% dos indivíduos mostraram resultados de IQCODE compatíveis com demência, sendo classificados no grupo com demência (GD): 87,5% desses pacientes tinham achados neuropatológicos correspondentes a patologia cerebral Alzheimer-símile (ALBP). Entre os pacientes do grupo sem demência (GSD), 16,7% apresentaram critérios neuropatológicos para ALBP. Todos os indivíduos do GD tinham depósitos de mais de um tipo de proteína no CE. A associação proteica mais comum foi tau hiperfosforilada e proteína beta-amiloide (87,5%). DISCUSSÃO: A maioria dos indivíduos com demência apresentaram achados neuropatológicos de ALBP e um indivíduo, que não tinha evidências de demência, apresentou achados compatíveis com ALBP, caracterizando um estágio pré-clínico. Este trabalho sugere que depósitos de um único tipo de proteína anômala são achados normais do cérebro em envelhecimento, enquanto mais de um tipo de proteínas ou a presença combinada de depósitos proteicos anômalos indica manifestações de demência.

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil / Achados neuropatológicos no córtex entorrinal de encéfalos de indivíduos acima de 50 anos e sua correlação com demência numa amostra do Sul do Brasil

ABSTRACT. Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

RESUMO. Introdução: Este trabalho visa avaliar alterações neurodegenerativas detectadas por depósitos proteicos anormais em Córtex Entorrinal (CE) de indivíduos acima de 50 anos e correlacionar os achados com suspeição de demência detectada por meio do IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly). Métodos: Catorze encéfalos foram submetidos à técnica imuno-histoquímica para diferentes proteínas (beta-amiloide, tau, alfa-sinucleína e fosfo-TDP-43) e esses dados foram comparados com os valores obtidos pelo IQCODE. Resultados: 57% dos indivíduos mostraram resultados de IQCODE compatíveis com demência, sendo classificados no grupo com demência (GD): 87,5% desses pacientes tinham achados neuropatológicos correspondentes a patologia cerebral Alzheimer-símile (ALBP). Entre os pacientes do grupo sem demência (GSD), 16,7% apresentaram critérios neuropatológicos para ALBP. Todos os indivíduos do GD tinham depósitos de mais de um tipo de proteína no CE. A associação proteica mais comum foi tau hiperfosforilada e proteína beta-amiloide (87,5%). Discussão: A maioria dos indivíduos com demência apresentaram achados neuropatológicos de ALBP e um indivíduo, que não tinha evidências de demência, apresentou achados compatíveis com ALBP, caracterizando um estágio pré-clínico. Este trabalho sugere que depósitos de um único tipo de proteína anômala são achados normais do cérebro em envelhecimento, enquanto mais de um tipo de proteínas ou a presença combinada de depósitos proteicos anômalos indica manifestações de demência.

Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study.

With the increase in life expectancy in Brazil, concerns have grown about the most prevalent diseases in elderly people. Among these diseases are neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Protein deposits related to the development of these diseases can pre-date the symptomatic phases by years. The tau protein is particularly interesting: it might be found in the brainstem and olfactory bulb long before it reaches the limbic cortex, at which point symptoms occur. Of the 14 brains collected in this study, the tau protein was found in the brainstems of 10 (71.42%) and in olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of Alzheimer's disease (AD), 6 presented tau deposits in some region of the brainstem. Our data support the idea of the presence of tau protein in the brainstem and olfactory bulb in the earliest stages of AD.

Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study / Alterações neurodegenerativas no tronco cerebral e bulbo olfatório em indivíduos acima de 50 anos: um estudo descritivo

With the increase in life expectancy in Brazil, concerns have grown about the most prevalent diseases in elderly people. Among these diseases are neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Protein deposits related to the development of these diseases can pre-date the symptomatic phases by years. The tau protein is particularly interesting: it might be found in the brainstem and olfactory bulb long before it reaches the limbic cortex, at which point symptoms occur. Of the 14 brains collected in this study, the tau protein was found in the brainstems of 10 (71.42%) and in olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of Alzheimer’s disease (AD), 6 presented tau deposits in some region of the brainstem. Our data support the idea of the presence of tau protein in the brainstem and olfactory bulb in the earliest stages of AD.

Com o aumento da expectativa de vida no Brasil e no mundo, crescem as preocupações com as doenças mais prevalentes entre os idosos, dentre elas as doenças neurodegenerativas (DN) como a doença de Alzheimer (DA) e a doença de Parkinson (DP). Sabe-se que os depósitos proteicos relacionados com o desenvolvimento destas doenças podem preceder a fase sintomática em anos. A proteína tau é de particular interesse, uma vez que parece ser encontrada no tronco encefálico e bulbo olfatório muito antes de atingir o córtex límbico, quando ocorrem os primeiros sintomas. Dos 14 encéfalos coletados neste estudo, a proteína tau foi encontrada, no tronco encefálico, em 10 (71,42%) e no bulbo olfatório em 3 de 11. Dos 7 indivíduos que tiveram diagnóstico final de DA, todos apresentavam depósitos de tau em alguma região do tronco encefálico. Nossos dados estão de acordo com a literatura mais recente, que tem confirmado a presença de proteína tau no tronco encefálico e bulbo olfatório nos estágios mais precoces da DA.

Variáveis maternas e paternas nas síndromes cromossômicas encontradas na base de dados do estudio colaborativo Latino Americano de Malformaciones Congénitas / Maternal and paternal variables in chromosomal syndromes found in the data base of the estudio colaborativo Latino Americano de Malformaciones Congénitas –Latin American Collaborative Study of Congenital Malformations

Síndromes cromossômicas são raras, porém graves e, em geral, de prognóstico reservado, o que vai ao encontro da necessidade de uma maior investigação a respeito das suas prováveis etiologias. O objetivo desse estudo é comparar os resultados a partir da base de dados do Estudo Colaborativo Latino-Americano de Malformacões Congênitas (ECLAMC) em nascidos vivos (NV) do Complexo Hospitalar da Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA) com aqueles já descritos e, a partir disso, considerar hipóteses causais para essas síndromes. Métodos: Estudo de caso-controle, com dados de obtidos através dos questionários do banco de dados do ECLAMC da maternidade do ISCMPA. Caso foi definido como recém-nascidos RN com qualquer anormalidade morfológica detectada ao nascimento. Todos os casos NV foram pareados com um controle, não malformado e de igual sexo que nasceu no mesmo hospital imediatamente depois do recém-nascido malformado. Resultados: Em um total de 259 RNs malformados (MF), foram encontrados 18 com malformações cromossômicas, sendo 16 com Síndrome de Down, 1 com Síndrome de Turner, e 1 com Síndrome de Pierre Robin. Dentre as variáveis analisadas, observou-se que RN vivos com malformações cromossômicas possuíam peso menor (P=0,002), eram em número maior de meninas (P<<0,01), nasceram com idade gestacional menor (P=0,043), possuíam pais com idade maior (P<<0,01 para mães e P=0,012 para pais) e mães que fumaram (P<<0,01) e beberam mais álcool (P=0,011) mais, que o grupo controle. Conclusão: As variáveis materno-paterno-dependentes parecem influenciar o número de RN que apresentam anomalias cromossômicas.

Although chromosomal syndromes are rare, they are serious and generally of poor prognosis, which meets the need for more research about their probable etiologies. The aim of this study is to compare the results from the database of the Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC) - Latin American Collaborative Study of Congenital Malformations in live-born infants (LBI) of the Hospital Complex of the Santa Casa de Misericordia of Porto Alegre (ISCMPA) with those already described and, from there, consider causal hypotheses for these syndromes. Methods: A case-control study with data obtained from questionnaires of the ECLAMC database in the Maternity Hospital of ISCMPA. A case was defined as a newborn (NB) with any morphological abnormalities detected at birth. All cases were matched with a non-malformed control of the same sex born in the same hospital immediately after the malformed NBs. Results: From a total of 259 malformed (MF) NBs, 18 had chromosomal malformations, 16 of which Down Syndrome, 1 Turner Syndrome, and 1 Pierre Robin Syndrome. Among the variables analyzed, we found that LBI with chromosomal abnormalities had lower weight (p = 0.002), were more likely females (p <<0.01), were born at lower gestational age (p = 0.043), and were born to older parents (p <<0.01 for mothers and p = 0.012 for fathers) and more likely to mothers who smoked (p <<0.01) and drank (p = 0.011) than the control group. Conclusion: The maternal-paternal-dependent variables seem to influence the number of NBs who have chromosomal abnormalities.

Diagnosis of Alzheimers disease in Brazil: supplementary exams / Diagnóstico de doença de Alzheimer no Brasil: exames complementares

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimers disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or preferably magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou ? preferencialmente ? ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência. O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.

Diagnóstico de doença de Alzheimer no Brasil: exames complementares / Diagnosis of Alzheimer's disease in Brazil: additional tests

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou - preferencialmente - ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência.O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams.

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer's disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or - preferably - magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou ­ preferencialmente ­ ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência. O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.

Early post-natal iron administration induces astroglial response in the brain of adult and aged rats.

This study was aimed to investigate neuropathological changes in adult and aged rats subjected to supplementary iron administration in a critical postnatal period to study the contribution of environmental risk factors to the pathogenesis of neurodegenerative disorders. Ten rats received a single daily oral administration of iron (10 mg/kg) between 12th and 14th post-natal days; nine rats received vehicle (sorbitol 5% in water) in the same period. Five iron-treated and three sorbitol-treated rats were killed at the age of 3 months while five iron-treated and six sorbitol-treated rats were killed at age of 24 months and their brains processed for immunohistochemistry. Increased astrocytosis, revealed by densitometry of GFAP-immunoreactive astrocytes, was found in aged (24 months) iron-treated rats in the substantia nigra and striatum and in the hippocampus of adult (3 months) iron-treated rats when compared to age-matching controls. Decreased densitometry of neurons, revealed by neuronal nucleus immunohistochemistry, was found in aged (24 months) iron-treated rats in substantia nigra and striatum when compared to age-matching controls. These findings suggest that transient dietary iron supplementation during the neonatal period is associated to cellular imprinting in the brain later in life.

Neonatal iron treatment increases apoptotic markers in hippocampal and cortical areas of adult rats.

Oxidative stress, cellular damage, and neuronal apoptosis are believed to underlie the progressive cognitive decline that accompanies natural aging and to be exacerbated in neurodegenerative diseases. Over the years, we have consistently demonstrated that iron neonatal treatment induces oxidative stress and memory deficits in adult rats, but the mechanisms underlying these effects remained undefined. The purpose of this study was to examine whether neonatal iron overload was associated with apoptotic cell death in adult and old rats. We analyzed Par-4 and caspase-3 immunoreactivity in specific brain areas including the hippocampus CA1, CA3 and dentate gyrus (DG), the adjacent cortex and the striatum in adult (3 months-old) and aged (24 months-old) rats from control (vehicle-treated) and neonatally iron-treated groups. Neonatal iron treatment consisted of a daily oral administration of 10 mg/kg of Fe(+2), for three consecutive days, from post-natal 12-14. Control aged animals showed increased levels of both markers when compared to untreated adult animals. When adults were compared, iron-treated animals presented significantly higher Par-4 and caspase-3 immunoreactivities in CA1, CA3 and cortex. In the DG, this effect was statistically significant only for Par-4. Interestingly, when control and iron-treated aged animals were compared, a significant decrease in both apoptotic markers was observed in the later groups in the same areas. These results may be interpreted as an acceleration of aging progressive damages caused by iron overload and may contribute to a better understanding of the damaging potential of iron accumulation to brain function and the resulting increased susceptibility to neurodegeneration.

As diversas faces da síndrome demencial: como diagnosticar clinicamente?: [revisão] / The several faces of dementia syndrome: how to diagnose clinically?: [review]

Objetivos: a presente revisão descreve aspectos clínicos relacionados às diferentes síndromes demenciais, objetivando tornar comum, no meio médico, o conhecimento das nuanças que permeiam o diagnóstico diferencial dessas afecções. Fonte de Dados: foi realizada uma revisão da literatura através das bases de dados Medline, Ovid e Scopus até outubro de 2009, assim como de livros-texto. Artigos com enfoque na fisiopatogenia e na patologia não foram priorizados, tendo em vista os objetivos deste estudo. Síntese dos Dados: este artigo revisa aspectos dealgumas síndromes demenciais reversíveis e irreversíveis, como Doença de Alzheimer e Demência Vascular, enfocando principalmente as características clínicas e diagnósticas que as tornam entidades distintas. Conclusões: a literatura sugere que o processo diagnóstico das síndromes demenciais assenta-se fundamentalmente na clínica, priorizando uma avaliação rigorosa do estado mental. Entretanto, a avaliação por neuroimagem e exames laboratoriais tem participação considerável em determinar a causa subjacente ao quadro demencial, revelando peculiaridades que podem nortear o diagnóstico diferencial. Diagnosticar diferentes etiologias é importante para o prognóstico e conduta terapêutica específica.

Aims: This review describes the clinical aspects related to different dementia syndromes, aiming to become common in the medical , the knowledge of the nuances that permeate the differential diagnosis of these disorders. Data Source: A review of literature published up to October 2009 was conducted on Medline, Ovid, and Scopus databases, as well as on textbooks. Articles that focused on the pathogenesis and pathology were not prioritized, given the objectives of this study. Summary of the Findings: This article reviews some aspects of reversible and irreversible dementia syndromes, such as Alzheimer?s disease and Vascular Disease, focusing on the clinic and diagnostic features that make them distinct entities. Conclusions: The literature suggests that the diagnostic process of dementia syndromes is based mainly on clinical practice, prioritizing a rigorous assessment of mental status. However, neuroimaging evaluation and laboratory tests have considerable input in determining the underlying cause of dementia, revealing peculiarities that can guide the differential diagnosis. The diagnosis of different etiologies is important to the prognosis and the specific therapeutic approach.

Effects of increased iron intake during the neonatal period on the brain of adult AbetaPP/PS1 transgenic mice.

The present study was aimed to investigate neuropathological changes in AbetaPP/PS1 transgenic mice (Tg), as a model of Alzheimer's disease, subjected to supplementary iron administration in a critical postnatal period, in order to reveal the interaction of genetic and environmental risk factors in the pathogenesis of the disease. Twelve Tg and 10 wild-type (Wt) littermates were administered iron between the 12th and 14th post-natal days (TgFe, WtFe); 11 Tg and 15 Wt received vehicle (sorbitol 5%) alone in the same period (TgSb, WtSb). Mice were killed at the age of six months and processed for morphological and biochemical studies. No modifications in amyloid-beta burden were seen in iron-treated and non-iron-treated AbetaPP/PS1 mice. No differences in microglial reactions were observed when comparing the four groups of mice. Yet increased astrocytosis, as revealed by densitometry of GFAP-immunoreactive astrocytes, and increased expression levels of GFAP, as revealed by gel electrophoresis and western blotting, were found in iron-treated mice (both Tg and Wt) when compared with TgSb and WtSb. This was accompanied by significant changes in brain fatty acid composition in AbetaPP/PS1 mice that led to a lower membrane peroxidizability index and to reduced protein oxidative damage, as revealed by reduced percentages of the oxidative stress markers: glutamic semialdehyde, aminoadipic semialdehyde, Nepsilon-carboxymethyl-lysine, Nepsilon-carboxyethyl-lysine, and Nepsilon-malondialdehyde-lysine. These findings demonstrate that transient dietary iron supplementation during the neonatal period is associated with cellular and metabolic imprinting in the brain in adult life, but it does not interfere with the appearance of amyloid plaques in AbetaPP/PS1 transgenic mice.

Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

BACKGROUND: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurrence of Alzheimer's disease (AD) is still controversial. OBJECTIVE: To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease. METHOD: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated analysis adjust by Mantel-Haenszel method. RESULTS: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002) The odds ratio increased exponentially with the increased number of E4 allele (chi2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. CONCLUSION: The APOE4 is a risk factor and demonstrated a dose-dependent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.

Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

INTRODUÇÃO: O papel do polimorfismo do gene da metilenotetrahidrofolato redutase (MTHFR) como um fator de risco para demência de Alzheimer (DA) é controverso ainda. OBJETIVO: Verificar a associação entre os polimorfismos da MTHFR e apolipoproteína E (APOE) e DA. MÉTODO: O trabalho foi conduzido como um estudo caso-controle. Trinta pacientes com DA provável foram incluídos no grupo caso. Vinte e nove indivíduos sem demência comprovadas por testes neuropsicológicos, emparelhados pela idade, sexo, cor e nível educacional constituíram o grupo controle. DNA foi isolado de leucócitos periféricos extraídos de sangue venoso anticoagulado. Genótipos de APOE e MTHFR foram realizados por amplificação de DNA e digestão. As freqüências dos genótipos da APOE e MTHFR foram submetidas ao teste do chi-quadrado corrigido pelo teste de Fisher; os genótipos da APOE, ao teste do chi-quadrado com tendência linear e as freqüências da MTHFR mutante e DA à análise estratificada corrigida pelo método de Mantel-Haenszel. RESULTADOS: Houve diferença significativa entre APOE4 e APOE2 nos grupos (p=0,002). O odds ratio aumentou exponencialmente com o aumento do número de alelo E4 (teste c2 com tendência linear). Nenhuma diferença significativa foi detectada nos genótipos da MTHFR em ambos grupos caso e controle. CONCLUSÃO: O alelo APOE4 é um fator de risco e demonstrou efeito dose-dependente enquanto o alelo E2 conferiu proteção para DA. A mutação da MTHFR não teve correlação dom DA.

Avaliaçäo neurológica evolutiva e das funçöes corticais numa amostra de crianças da primeira série / Evolutive neurological evaluation and cortical functions evaluation in a sample of children from the first grade of the elementary school

Os autores estudam 24 crianças que cursam pela primeira vez a primeira série do primeiro graú, mediante o exame neurológico clássico, bem como o do exame neurológico evolutivo e de provas para avaliar funçöes corticais. Analisam o desempenho escolar em relaçäo ao desempenho no exame neurológico evolutivo e no exame das funçöes corticais. Comparam e discutem os resultados. Concluem que o uso desses dois instrumentos é capaz de discriminar o bom e o mau desempenho escolar

Um modelo de avaliaçäo das funçöes corticais / An evaluation model of the cortical functions

Os autores propöem protocolo elaborado para padronizar a avaliaçäo das funçöes corticais superiores, capaz de se constituir em elemento de localizaçäo de patologia cortical