The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer's disease.

Alzheimer's disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEε4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEε4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan(®) assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEε4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEε4 were strongly associated with AD [OR 11.13; 95 % CI (4.25-29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEε4 in this sample of AD patients. The presence of TGG haplotype and APOEε4 significantly increased the risk of developing the disease, showing an synergistic effect.

Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

BACKGROUND/AIMS: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). METHODS: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. RESULTS: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. DISCUSSION: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α) with diagnosis of delirium in oncology inpatients.

OBJECTIVE: To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients. METHODS: Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation. RESULTS: Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups. CONCLUSION: A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α) with diagnosis of delirium in oncology inpatients

Objective:To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients.Methods:Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation.Results:Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups.Conclusion:A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

DNA methyltransferase haplotype is associated with Alzheimer's disease.

Epigenetic mechanisms have been implicated in syndromes associated with neuropsychiatric disorders, but little is known about the role of epigenetics in Alzheimer's disease (AD). DNA methylation, one of the main epigenetic mechanisms, is a complex process carried out by specific enzymes, such as DNMT1 and DNMT3B. This study aimed to investigate the association between DNMT1 and DNMT3B polymorphisms and AD. Two hundred and ten elderly subjects (108 healthy controls and 102 with AD-NINCDS/ARDA, DSM-IV-TR criteria) were assessed. DNA was obtained from whole blood, and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560, rs759920 (DNMT1) and rs998382, rs2424913, rs2424932 (DNMT3B). For both genes, the polymorphisms were in strong linkage disequilibrium. Carriers of the DNMT3B TGG haplotype were associated with AD (OR=3.03, 95% CI 1.63 to 5.63, P<0.001). No significant difference between AD and the control group were observed for DNMT1 polymorphisms. This study is one of the first describing a significant association between DNMT3B polymorphisms and AD. This enzyme, which is responsible for methylation in a general way, may be involved in AD.

Perfil lipídico e obesidade em homens de um município da Região Sul do Brasil / Lipid profile and obesity in men from a county of the South

Objetivos: Avaliar o perfil lipídico e sua relação com obesidade em homens de Flores da Cunha, Rio Grande do Sul.Métodos: Um estudo transversal de base populacional selecionou homens moradores do município de Flores da Cunha, localizado na região nordeste do Rio Grande do Sul. Informações sociodemográficas foram obtidas por meio de um questionário. A coleta de amostras de sangue foi feita em um centro de saúde a as análises bioquímicas foram realizadas no laboratório de Toxicologia do Centro Universitário Metodista do IPA. Resultados: Foram estudados 368 homens, cuja idade variou de 25 a 83 anos, com média de 49,3 anos. As análises bioquímicas mostraram os seguintes valores médios: colesterol total 211,3 mg/dL; triglicerídeos 178,3 mg/dL; colesterol HDL (high density lipoprotein ? lipoproteína de alta densidade) 46,4 mg/dL; e colesterol LDL (low density lipoprotein ? lipoproteína de baixa densidade) 132,4 mg/dL. Houve diferença significativa quando comparados os resultados dos triglicerídeos em grupos com índice de massa corporal (IMC) normal e obesos (p<0,001) e entre grupos com sobrepeso e obesos (p=0,001); o colesterol HDL diferiu entre grupos com IMC normal e sobrepeso (p<0,001) e entre IMC normal e obesos (p<0,001). Os indivíduos eutróficos apresentam os menores valores de triglicerídeos e os maiores de colesterol HDL.Conclusões: Os dados obtidos, com aproximadamente 80% da amostra apresentando excesso de peso e um percentual relevante apresentando níveis plasmáticos elevados de lipídios, causam preocupação, considerando a morbimortalidade a que estão ligados esses fatores.

Aims: To evaluate the lipid profile and its relationship with obesity in men from Flores da Cunha, Rio Grande do Sul.Methods: A population-based cross-sectional study included men living in the county of Flores da Cunha, located in northeastern Rio Grande do Sul, the southernmost state in Brazil. Sociodemographic data were obtained through aquestionnaire. Blood samples were taken at a health center and the biochemical analyzes were performed in the laboratoryof Toxicology of the Centro Universitário Metodista do IPA.Results: We studied 368 men whose ages ranged from 25 to 83 years, mean 49.3 years. Biochemical analysis showedthe following average values: total cholesterol 211.3 mg/dL, triglycerides 178.3 mg/dL, HDL (high density lipoprotein) cholesterol 46.4 mg/dL, and LDL (low-density lipoprotein) cholesterol 132.4 mg/dL. There were significant differenceswhen comparing results of triglycerides in body mass index (BMI) normal and obese subjects (p<0.001) and amongoverweight and obese groups (p=0.001). HDL cholesterol differed between groups with normal BMI and overweight(p<0.001) and between obese and normal BMI (p<0.001). The normal individuals had the lowest values of triglyceridesand higher HDL cholesterol.Conclusions: The data of approximately 80% of the sample presenting overweight and a relevant percentage presentingelevated plasma levels of lipids are cause for concern, considering the morbidity and mortality to which these factors are linked.

Neuropsychiatric symptoms as the main determinant of caregiver burden in Alzheimer's disease / Sintomas neuropsiquiátricos como o principal determinante da sobrecarga do cuidador na doença de Alzheimer

Abstract. Caregiver burden is common in Alzheimer's disease (AD), decreasing the quality of life among caregivers and patients. Projections of aging and aging-related diseases such as AD in developing countries justify additional data about this issue because people living in these countries have shown similarly high levels of caregiver strain as in the developed world. Objective: The aim of this study was to analyze the association of AD caregivers' burden with patients' neuropsychiatric symptoms (NPS), cognitive status, severity of dementia, functional capacity, caregiver sociodemographic characteristics, and the characteristics of care provided by caregivers. Methods: A cross-sectional study was conducted in a sample of 39 consecutive AD patients and their primary caregivers. NPS were evaluated using the Neuropsychiatric Inventory (NPI). Severity of dementia was assessed with the Clinical Dementia Rating (CDR) scale. Functional capacity was assessed using the Katz and Lawton scales. The burden level was rated using the Burden Interview (BI). Sociodemographic characteristics of caregivers and the characteristics of care provided by them were evaluated. The Mann-Whitney U-test, Kruskal-Wallis test and Spearman's rho coefficient were performed. Results: The BI had a moderate correlation with NPI intensity (rho=0.563), p<001. Female caregivers reported a greater level of burden (p=0.031) than male caregivers. The other variables were not significantly associated to caregiver burden. Conclusion: NPS were the main determinant of burden in primary caregivers of AD patients. This result underscores the need for prevention and treatment of these symptoms. Sex also had an effect on caregiver burden, but the small male sample in this study precludes the generalization of this finding.

Resumo. Sobrecarga no cuidador é comum na doença de Alzheimer (DA), diminuindo a qualidade de vida dos cuidadores e pacientes. As projeções de envelhecimento e doenças relacionadas ao envelhecimento como a DA nos países em desenvolvimento justificam dados adicionais sobre esta questão, porque as pessoas que vivem nestes países têm apresentado níveis semelhantes de sobrecarga no cuidador tão alto quanto no mundo desenvolvido. Objetivo: O estudo teve como objetivo analisar a associação da sobrecarga em cuidadores de pacientes com DA com sintomas neuropsiquiátricos (NPS) dos pacientes, estatus cognitivo, gravidade da demência, capacidade funcional, características sociodemográficas do cuidador e as características dos cuidados prestados pelos cuidadores. Métodos: Um estudo transversal foi realizado em uma amostra de 39 pacientes consecutivos de DA e seus cuidadores primários. NPS foram avaliados através do Inventário Neuropsiquiátrico (NPI). A gravidade da demência foi avaliada com a escala Clinical Dementia Rating (CDR). A capacidade funcional foi avaliada com as escalas de Katz e Lawton. O nível de sobrecarga foi avaliada utilizando a escala Burden Interview (BI). Características sociodemográficas dos cuidadores e as características de atendimento prestado por eles foram avaliadas. Mann-Whitney, Kruskal-Wallis e coeficiente rho de Spearman foram calculados. Resultados: BI apresentou correlação moderada com a intensidade do NPI (rho=0,563), p<001. Cuidadoras mulheres relataram maior nível de sobrecarga (p=0,031) do que cuidadores do sexo masculino. As demais variáveis não foram significativamente associados à sobrecarga do cuidador. Conclusão: NPS foram o principal determinante da sobrecarga do cuidador de pacientes com DA. Esse resultado reforça a necessidade de prevenção e tratamento desses sintomas. Sexo também teve um efeito sobre a sobrecarga do cuidador, mas a pequena amostra do sexo masculino neste estudo evita a generalização dessa constatação.

Neuropsychiatric symptoms as the main determinant of caregiver burden in Alzheimer's disease.

Caregiver burden is common in Alzheimer's disease (AD), decreasing the quality of life among caregivers and patients. Projections of aging and aging-related diseases such as AD in developing countries justify additional data about this issue because people living in these countries have shown similarly high levels of caregiver strain as in the developed world. OBJECTIVE: The aim of this study was to analyze the association of AD caregivers' burden with patients' neuropsychiatric symptoms (NPS), cognitive status, severity of dementia, functional capacity, caregiver sociodemographic characteristics, and the characteristics of care provided by caregivers. METHODS: A cross-sectional study was conducted in a sample of 39 consecutive AD patients and their primary caregivers. NPS were evaluated using the Neuropsychiatric Inventory (NPI). Severity of dementia was assessed with the Clinical Dementia Rating (CDR) scale. Functional capacity was assessed using the Katz and Lawton scales. The burden level was rated using the Burden Interview (BI). Sociodemographic characteristics of caregivers and the characteristics of care provided by them were evaluated. The Mann-Whitney U-test, Kruskal-Wallis test and Spearman's rho coefficient were performed. RESULTS: The BI had a moderate correlation with NPI intensity (rho=0.563), p<001. Female caregivers reported a greater level of burden (p=0.031) than male caregivers. The other variables were not significantly associated to caregiver burden. CONCLUSION: NPS were the main determinant of burden in primary caregivers of AD patients. This result underscores the need for prevention and treatment of these symptoms. Sex also had an effect on caregiver burden, but the small male sample in this study precludes the generalization of this finding.

Sobrecarga no cuidador é comum na doença de Alzheimer (DA), diminuindo a qualidade de vida dos cuidadores e pacientes. As projeções de envelhecimento e doenças relacionadas ao envelhecimento como a DA nos países em desenvolvimento justificam dados adicionais sobre esta questão, porque as pessoas que vivem nestes países têm apresentado níveis semelhantes de sobrecarga no cuidador tão alto quanto no mundo desenvolvido. OBJETIVO: O estudo teve como objetivo analisar a associação da sobrecarga em cuidadores de pacientes com DA com sintomas neuropsiquiátricos (NPS) dos pacientes, estatus cognitivo, gravidade da demência, capacidade funcional, características sociodemográficas do cuidador e as características dos cuidados prestados pelos cuidadores. MÉTODOS: Um estudo transversal foi realizado em uma amostra de 39 pacientes consecutivos de DA e seus cuidadores primários. NPS foram avaliados através do Inventário Neuropsiquiátrico (NPI). A gravidade da demência foi avaliada com a escala Clinical Dementia Rating (CDR). A capacidade funcional foi avaliada com as escalas de Katz e Lawton. O nível de sobrecarga foi avaliada utilizando a escala Burden Interview (BI). Características sociodemográficas dos cuidadores e as características de atendimento prestado por eles foram avaliadas. Mann-Whitney, Kruskal-Wallis e coeficiente rho de Spearman foram calculados. RESULTADOS: BI apresentou correlação moderada com a intensidade do NPI (rho=0,563), p<001. Cuidadoras mulheres relataram maior nível de sobrecarga (p=0,031) do que cuidadores do sexo masculino. As demais variáveis não foram significativamente associados à sobrecarga do cuidador. CONCLUSÃO: NPS foram o principal determinante da sobrecarga do cuidador de pacientes com DA. Esse resultado reforça a necessidade de prevenção e tratamento desses sintomas. Sexo também teve um efeito sobre a sobrecarga do cuidador, mas a pequena amostra do sexo masculino neste estudo evita a generalização dessa constatação.