Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain.

Aging is a complex process strongly determined by genetics. Previous reports have shown that the genome of neuronal cells displays somatic genomic mosaicism including DNA copy number variations (CNVs). CNVs represent a significant source of genetic variation in the human genome and have been implicated in several disorders and complex traits, representing a potential mechanism that contributes to neuronal diversity and the etiology of several neurological diseases and provides new insights into the normal, complex functions of the brain. Nonetheless, the features of somatic CNV mosaicism in nondiseased elderly brains have not been investigated. In the present study, we demonstrate a highly significant increase in the number of CNVs in nondiseased elderly brains compared to the blood. In two neural tissues isolated from paired postmortem samples (same individuals), we found a significant increase in the frequency of deletions in both brain areas, namely, the frontal cortex and cerebellum. Also, deletions were found to be significantly larger when present only in the cerebellum. The sizes of the variants described here were in the 150-760 kb range, and importantly, nearly all of them were present in the Database of Genomic Variants (common variants). Nearly all evidence of genome structural variation in human brains comes from studies detecting changes in single cells which were interpreted as derived from independent, isolated mutational events. The observations based on array-CGH analysis indicate the existence of an extensive clonal mosaicism of CNVs within and between the human brains revealing a different type of variation that had not been previously characterized

Morphometric brain changes during aging: Results from a Brazilian necropsy sample.

The present study aimed to establish the morphometric brain changes during aging in a necropsy series from Brazil and determine whether sexual dimorphisms interfere in these changes. Methods:A cross-sectional study was conducted at the São Paulo Autopsy Service in Brazil where, after informed consent, data was gathered from next of kin interview with reference to clinical status prior to death. Brain weight, volume and density measurements were taken and then adjusted for head circumference. Descriptive statistics and tests of hypothesis and correlations were applied, considering a p-value of 0.05. Results:414 subjects, mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain weight of the sample was 1219.2g±140.9and mean volume was 1217mL±152.3. The mean brain density of the sample was 1.0g/mL±0.09. Values differed between males and females in terms of weight and volume. Brain weight decreased during aging by about 45g per decade (r= -0.300; p<0.01) and volume by about 43mL (r= -0.278; p<0.00). Mean density of the sample was 1.0 g/mL in both genders. Conclusions:Brain weight and volume (with or without corrections) decreased during aging, and these reductions were more pronounced in women. Density remained unchanged for both genders. Further studies are needed to investigate factors associated to these reductions

Perceptions of dementia amongst the general public across Latin America: a systematic review

Introduction: Perceptions of dementia are important determinants of support, treatment and care received in the dementia community. Understanding these perceptions are vital for regions such as Latin America, where there is a rapid increase in people living with dementia. The aim of this study is to review and synthesise the general public’s perceptions of dementia in Latin America, what factors are associated with these perceptions, and how they differ between countries in the region. Methods: Searches were completed across five databases (Medline, SCOPUS, PsychINFO, SciELO, and WoS). Studies were required to capture attitudes or knowledge of dementia in the general public residing within Latin America. English, Spanish and Portuguese search terms were used. Results were synthesised narratively. Results: About 1574 unique records were identified. Following lateral searches, de-duplication and screening, six articles (four studies) met the inclusion criteria for this review. All the studies were quantitative research from Brazil (median, n = 722). There was evidence of a limited to moderate knowledge of dementia, though a significant minority had negative or stigmatising attitudes. Only higher levels of education were consistently associated with better attitudes and knowledge of dementia in the region. Conclusion: There is a need for more in-depth research about attitudes of the general public across Latin America, particularly outside of São Paulo state, Brazil. There appears to be a greater need to raise awareness of dementia amongst less educated Latin American groups

La hipertensión arterial es causa subyacente de muerte evaluada en la autopsia de individuos

Objetivo: Analizar la hipertensión y su relación con las causas de muerte identificadas por la autopsia. Método: Estudio transversal, que analizó a 356 participantes del Biobanco para Estudios en el Envejecimiento, con edad mayor a 50 años, autopsiados en el Servicio de Verificación de Defunciones entre los años 2004 y 2014. Una entrevista clínica fue realizada con el informante del fallecido. La hipertensión fue definida por el relato de la enfermedad y/o uso de medicación antihipertensiva por el informante del fallecido. Se llevaron a cabo análisis descriptivos y asociaciones bivariadas y multivariables. Resultados: La prevalencia de hipertensión arterial fue del 66,2% y fue la segunda causa básica de defunción (25,6%) identificada en la autopsia, precedida de aterosclerosis (37,8%). Las variables asociadas con la hipertensión fueron: género femenino (OR = 2,30 (1,34-3,90); tener a una pareja [OR = 0,55 (0,32-0,92)]; índice de masa corporal [OR = 1,14 (1,08-1,22)] e historia de diabetes [OR = 2,39 (1,34-4,27)]. Conclusión: La prevalencia de hipertensión fue elevada y representó la segunda causa básica de defunción más frecuente. El uso de la autopsia como regla de oro para definir la causa de la muerte confirmó la relevancia de la hipertensión como un problema de salud pública.Objective: To analyze hypertension and its relationship with the causes of death identified by the autopsy. Method: Cross-sectional study analyzed 356 participants belonging to the Brazilian Aging Brain Study Group, over 50 years of age, autopsied at the Sao Paulo Autopsy Service between 2004 to 2014. A clinical interview was conducted with the informant of the deceased. Hypertension was defined by reporting the disease and/or use of antihypertensive medication, by the informant of the deceased. Descriptive analyzes and bivariate and multivariable associations were performed. Results: The prevalence of hypertension was 66.2% and it was the second leading cause of death (25.6%) identified by autopsy, preceded by atherosclerosis (37.8%). The variables associated with hypertension were: female gender (OR=2.30 (1.34-3.90)); living with partner [OR=0.55 (0.32-0.92)]; Body Mass Index [OR=1.14 (1.08-1.22)] and history of diabetes [OR=2.39 (1.34-4.27)]. Conclusion: The prevalence of hypertension was high, and it was the second most common underlying cause of death. The gold standard for the definition of cause of death, the autopsy, shows important results, which confirmed the relevance of hypertension as a public health problem.Objetivo: Analisar a hipertensão e sua relação com as causas de morte identificadas pela autópsia. Método: Estudo transversal, que analisou 356 participantes do Biobanco para Estudos no Envelhecimento, com idade maior do que 50 anos, autopsiados no Serviço de Verificação de Óbitos entre os anos de 2004 a 2014. Uma entrevista clínica foi realizada com o informante do falecido. A hipertensão foi definida pelo relato da doença e/ou o uso de medicação anti-hipertensiva pelo informante do falecido. Foram realizadas análises descritivas e associações bivariadas e multivariáveis. Resultados: A prevalência de hipertensão arterial foi de 66,2% e foi a segunda causa básica de óbito (25,6%) identificada na autópsia, precedida de aterosclerose (37,8%). As variáveis associadas à hipertensão foram: gênero feminino (OR = 2,30 (1,34-3,90); ter um parceiro [OR = 0,55 (0,32-0,92)]; índice de massa corporal [OR = 1,14 (1,08-1,22)] e história de diabetes [OR = 2,39 (1,34-4,27)]. Conclusão: A prevalência de hipertensão foi elevada e representou a segunda causa básica de óbito mais frequente. O uso da autópsia como padrão-ouro para definir a causa da morte confirmou a relevância da hipertensão como um problema de saúde pública

Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study.

IntroductionAdiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study.Methods and analysisA sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and α=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80°C for future studies.Ethics and disseminationEthical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal

Potencial del VES-13 para identificar la esperanza de vida limitada de adultos mayores en centros de atención primaria

Objetivo: Investigar o potencial do instrumento Vulnerable Elders Survey para identificar idosos com expectativa de vida limitada, em ambientes de atenção primária à saúde. Método: Estudo transversal realizado em todas as (nove) unidades de saúde de Jataí, Goiás (Brasil), no período de julho a dezembro de 2018. Obteve-se uma amostra de 407 idosos, considerando uma população ≥ 60 anos. Os participantes responderam a um questionário sobre características sociodemográficas e clínicas, incluindo o Vulnerable Elders Survey e o índice de Suemoto. Testamos a associação entre a expectativa de vida limitada e o Vulnerable Elders Survey usando análise de regressão logística múltipla. Resultados: A idade média foi de 68,9 ± 6,6 anos, e 58,0% dos participantes eram mulheres. A pontuação média do Vulnerable Elders Survey foi de 2,0 ± 2,2, a pontuação média do índice de Suemoto foi de 31,5 ± 21,1%, e 17,2% dos participantes tinham expectativa de vida limitada. O Vulnerable Elders Survey foi associado a uma expectativa de vida limitada (OR = 1,57; p = < 0,0001). Conclusão: O instrumento Vulnerable Elders Survey foi capaz de identificar idosos com expectativa de vida limitada em ambientes de atenção primária à saúde, além de poder auxiliar na detecção de idosos que não se beneficiariam com a triagem e o controle estrito de doenças crônicas.Objective: To investigate the potential role of the Vulnerable Elders Survey to identify older adults with limited life expectancy in primary healthcare settings. Method: This cross-sectional study was performed in all (nine) healthcare units in Jatai, Goiás (Brazil) from July to December 2018. A sample size of 407 older adults was obtained considering an older population (≥ 60 years old). Participants answered a questionnaire about sociodemographic and clinical characteristics, including the Vulnerable Elders Survey and the Suemoto index. We tested the association between limited life expectancy and the Vulnerable Elders Survey using multiple logistic regression analysis. Results: The mean age was 68.9 ± 6.6 yo, and 58.0% were women. The mean score of the Vulnerable Elders Survey was 2.0 ± 2.2, the mean score of Suemoto index was 31.5 ± 21.1%, and 17.2% had limited life expectancy. The Vulnerable Elders Survey was associated with limited life expectancy (OR = 1.57; p = < 0.0001). Conclusion: The Vulnerable Elders Survey was able to identify older adults with limited life expectancy in primary healthcare settings and can play a role in detecting older adults who would not benefit from screening and strict control of chronic diseases.Objetivo: Investigar o potencial do instrumento Vulnerable Elders Survey para identificar idosos com expectativa de vida limitada, em ambientes de atenção primária à saúde. Método: Estudo transversal realizado em todas as (nove) unidades de saúde de Jataí, Goiás (Brasil), no período de julho a dezembro de 2018. Obteve-se uma amostra de 407 idosos, considerando uma população ≥ 60 anos. Os participantes responderam a um questionário sobre características sociodemográficas e clínicas, incluindo o Vulnerable Elders Survey e o índice de Suemoto. Testamos a associação entre a expectativa de vida limitada e o Vulnerable Elders Survey usando análise de regressão logística múltipla. Resultados : A idade média foi de 68,9 ± 6,6 anos, e 58,0% dos participantes eram mulheres. A pontuação média do Vulnerable Elders Survey foi de 2,0 ± 2,2, a pontuação média do índice de Suemoto foi de 31,5 ± 21,1%, e 17,2% dos participantes tinham expectativa de vida limitada. O Vulnerable Elders Survey foi associado a uma expectativa de vida limitada (OR = 1,57; p = < 0,0001). Conclusão: O instrumento Vulnerable Elders Survey foi capaz de identificar idosos com expectativa de vida limitada em ambientes de atenção primária à saúde, além de poder auxiliar na detecção de idosos que não se beneficiariam com a triagem e o controle estrito de doenças crônicas

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

Introduction: Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective: The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results: A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion: Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed

Post-Mortem diagnosis of dementia by informant interview.

The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an informant. Objectives:To ascertain the sensitivity and specificity of postmortem diagnosis based on informant interview compared against the diagnosis established at a memory clinic. Methods:A prospective study was conducted at the BBBABSG and at the Reference Center for Cognitive Disorders (RCCD), a specialized memory clinic of the Hospital das Clínicas, University of São Paulo Medical School. Control subjects and cognitively impaired subjects were referred from the Hospital das Clínicas to the RCCD where subjects and their informants were assessed. The same informant was then interviewed at the BBBABSG. Specialists' panel consensus, in each group, determined the final diagnosis of the case, blind to other center's diagnosis. Data was compared for frequency of diagnostic equivalence. For this study, the diagnosis established at the RCCD was accepted as the gold standard. Sensitivity and specificity were computed. Results:Ninety individuals were included, 45 with dementia and 45 without dementia (26 cognitively normal and 19 cognitively impaired but non-demented). The informant interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7% for the diagnosis of normal cognition. Conclusions:The informant interview used at the BBBABSG has a high specificity and sensitivity for the diagnosis of dementia as well as a high specificity for the diagnosis of normal cognition

Association between cognitive performance and self-reported glaucoma in middle-aged and older adults : a cross-sectional analysis of ELSA-Brasil

Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings

Validez del índice de katz para evaluar las actividades básicas de vida diaria por informantes en estudios neuropatológicos

OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.OBJETIVO Analisar as evidências de validade de constructo do Índice de Katz para a avaliação retrospectiva das Atividades Básicas de Vida Diária (AbVD) por informantes, para apoiar estudos neuropatológicos no envelhecimento. MÉTODO Por meio de estudo transversal foi analisada a capacidade funcional para as AbVD mensurada pelo Índice de Katz em 650 casos randomizados das bases de dados do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral (BEHGEEC). A amostra foi particionada em duas subamostras para as análises (N=325, cada) e então estratificada de acordo com o comprometimento cognitivo determinado pelo Escore Clínico de Demência (CDR). Foram realizadas análise fatorial, de consistência interna e de invariância. RESULTADOS A análise fatorial evidenciou um instrumento unidimensional com ótima consistência interna, em todos os grupos. Ótimos índices de ajuste foram obtidos após o tratamento de duas covariâncias, indicando adequação da escala para avaliar AbVD por informantes. A escala é invariante para o comprometimento cognitivo, o que significa que pode ser usada em indivíduos com ou sem comprometimento cognitivo. CONCLUSÃO O Índice de Katz apresenta validade de constructo para a avaliação retrospectiva das AbVD por informantes, com confiabilidade.OBJETIVO Analizar las evidencias de validez de constructo del Índice de Katz para la evaluación retrospectiva de las Actividades Básicas de Vida Diaria (AbVD) por informantes para apoyar estudios neuropatológicos en el envejecimiento. MÉTODO Por medio de estudio transversal se analizó la capacidad funcional para las AbVD mensurada por el Índice de Katz en 650 casos randomizados de las bases de datos del Banco de Encéfalos Humanos del Grupo de Estudios en Envejecimiento Cerebral (BEHGEEC). La muestra fue dividida en dos submuestras para los análisis (N=325, cada) y luego estratificada de acuerdo con el compromiso cognitivo determinado por la Escala de Clasificación de la Demencia Clínica (CDR). Se hicieron análisis factorial, de consistencia interna y de invariancia. RESULTADOS El análisis factorial evidenció un instrumento unidimensional con excelente consistencia interna, en todos los grupos. Excelentes índices de ajuste fueron obtenidos después del tratamiento de dos covariancias, indicando la adecuación de la escala para evaluar AbVD por informantes. La escala es invariante para el compromiso cognitivo, lo que significa que se puede utilizarla en individuos con o sin compromiso cognitivo. CONCLUSIÓN El Índice de Katz presenta validez de constructo para la evaluación retrospectiva de las AbVD por informantes, con confiabilidad