Association of Moderate and Vigorous Physical Activity With Cognitive Performance: Evidence From Brazil.

OBJECTIVE: It is estimated that 2% of dementia cases worldwide could be prevented with increases in physical activity. However, there is little evidence of the association between vigorous physical activity (VPA) and cognitive performance. This study aimed to investigate the association of moderate physical activity (MPA) and VPA with cognitive performance in older adults from the Brazilian Longitudinal Study of Aging (ELSI-Brasil). PATIENTS AND METHODS: Data from 7954 participants were analyzed. Mean age was 61.8 ± 9.2 years, 61.8% were women, and 44.3% were mixed races. Cognitive performance evaluated the memory, temporal orientation, and verbal fluency domains. A global composite z-score was derived from the tests. Physical activity was assessed by self-report. We used linear regression models to verify the association of MPA and VPA with cognitive performance. RESULTS: Compared with participants who did not meet the guidelines for MPA (<150 min/wk), those who met the guidelines (150 to 299 min/wk) and those who performed more than 2x the recommended amount of MPA (300 min or more/wk) had better global cognitive performance (ß = 0.163, 95% CI = 0.086, 0.241; P < 0.001; ß = 0.180, 95% CI = 0.107, 0.253, P < 0.001, respectively). We found no association between VPA and cognitive performance. CONCLUSION: There was no additional benefit of VPA for cognitive performance.

Association Between Subclinical Thyroid Dysfunction and Cognitive Decline: Findings From the ELSA-Brasil Study.

BACKGROUND: Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. METHODS: Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. RESULTS: In 9 524 participants (mean age 51.2 ±â€…8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (ß = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (ß = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (ß = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (ß = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline. CONCLUSIONS: An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Adherence to the planetary health diet and cognitive decline: findings from the ELSA-Brasil study.

The EAT-Lancet Commission proposed a planetary health diet to improve human health within planetary boundaries; however, little is known about the association between adherence to this diet and cognitive decline. We used data from three waves of the Brazilian Longitudinal Study of Adult Health to evaluate the association between the planetary health diet and cognitive decline using linear mixed-effects models. Here we show that in 11,737 participants (mean (s.d.) age 51.6 (9.0) years, 54% women and 53% white), higher adherence to the planetary health diet was associated with slower memory decline (P = 0.046) and that income was a modifier in this association (P < 0.001). Adherence to the planetary health diet was associated with slower decline of memory (P = 0.040) and global cognition (P = 0.009) in high-income participants. No association was found among low-income participants. The results of our study highlight that the promotion of healthy dietary patterns should take into consideration income barriers as well as differences in dietary habits to achieve high adherence.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study.

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1ß, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1ß (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1ß and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1ß (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Leisure-Time Physical Activity May Attenuate the Impact of Diabetes on Cognitive Decline in Middle-Aged and Older Adults: Findings From the ELSA-Brasil Study.

OBJECTIVE: To assess leisure-time physical activity (LTPA) as a modifier of the diabetes/cognitive decline association in middle-aged and older participants in the Estudo Longitudinal de Saude do Adulto (ELSA-Brasil) study. RESEARCH DESIGN AND METHODS: ELSA-Brasil is a cohort of 15,105 participants (age 35-74 years) enrolled between 2008 and 2010. We evaluated global cognitive function, summing the scores of six standardized tests evaluating memory and verbal fluency, including the Trail-Making Test, at baseline and follow-up. Incident cognitive impairment was defined as a global cognitive function score at follow-up lower than -1 SD from baseline mean. Participants reporting ≥150 min/week of moderate to vigorous LTPA at baseline were classified as physically active. We assessed the association of LTPA with global cognition change in those with diabetes in the context of our overall sample through multivariable regression models. RESULTS: Participants' (N = 12,214) mean age at baseline was 51.4 (SD 8.8) years, and 55.5% were women. During a mean follow-up of 8.1 (SD 0.6) years, 9,345 (76.5%) inactive participants and 1,731 (14.1%) participants with diabetes at baseline experienced faster declines in global cognition than those who were active (ß = -0.003, -0.004, and -0.002) and those without diabetes (ß = -0.004, -0.005, and -0.003), respectively. Diabetes increased the risk of cognitive impairment (hazard ratio [HR] 1.71; 95% Cl 1.22, 2.39) in inactive but not in active adults (HR 1.18; 95% CI 0.73, 1.90). Among participants with diabetes, those who were active showed a delay of 2.73 (95% CI 0.94, 4.51) years in the onset of cognitive impairment. CONCLUSIONS: In adults living with diabetes, LTPA attenuated the deleterious association between diabetes and cognitive function.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Rural-urban disparities in fruit and vegetable consumption and cognitive performance in Brazil

Objectives: Rural residents are exposed to many risk factors for poor diet quality, such as low socioeconomic status and food insecurity. However, the differences between urban and rural residents regarding the association of fruit and vegetable consumption with cognitive performance have not been explored. The aim of this study was to investigate the association of fruit and vegetable consumption with cognitive performance in urban and rural areas in a nationally representative sample of Brazilian older adults. Methods: The sample included 9,412 adults aged 50 years or older from the Brazilian Longitudinal Study of Aging (Estudo Longitudinal da Saúde dos Idosos Brasileiros [ELSI]). The association between consumption of fruits and vegetables and cognitive performance was evaluated using linear regression. Results: In 8,158 participants (mean age 61.6 ± 9.3 years, 54% women, 44% White, and 15% from rural areas), the mean frequency of fruit and vegetable consumption was 2.0 ± 1.3 times a day. Higher intake of fruits and vegetables was associated with better memory (β = 0.031, 95%CI 0.014-0.049), verbal fluency (β = 0.030, 95%CI 0.004-0.056), and global cognition (β = 0.035, 95%CI 0.015-0.055) performance in urban, but not rural residents (p for interaction = 0.036). Conclusion: Higher frequency of fruit and vegetable intake was associated with better cognitive performance in urban, but not in rural areas in Brazil.

Untangle the relationship of muscle mass and bone mineral content on handgrip strength: Results of ELSA-Brasil / Desvendando a relação entre massa muscular e conteúdo mineral ósseo na força de preensão palmar: Resultados do ELSA-Brasil

Abstract The study aims to investigate the independent association of muscle mass (MM) and bone mineral content (BMC) in the performance of the handgrip strength (HGS) test and whether there is effect modification by sex and age. In 12,491 participants from the ELSA-Brasil we estimated the associations between MM, BMC and HGS using linear regression models. All the analyses were performed for total population, also stratified for sex and age. For total population an interaction term was included between each explanatory variable of interest with sex and age to verify the presence of effect modification. We observed that the higher quintiles of MM and BMC were associated to an increasing in the mean of HGS compared to the first quintile, with greater magnitudes in men compared to women, also adults compared to elderly. When we estimated the independent effect of each exposure of interest, MM showed stronger effect in HGS in women, men and adults then BMC. In conclusion, we observed that higher amounts of MM and BMC are associated with higher HGS, regardless of sociodemographic characteristics, health conditions and lifestyle, with this effect being greater in men and adults.

Resumo O estudo tem como objetivo investigar a associação independente da massa muscular (MM) e conteúdo mineral ósseo (CMO) na realização do teste de força de preensão manual (FPM) e se há modificação do efeito por sexo e idade. Em 12.491 participantes do ELSA-Brasil estimamos as associações entre MM, CMO e FPM usando modelos de regressão linear. Todas as análises foram realizadas para a população total, também estratificada por sexo e idade. Para a população total foi incluído um termo de interação entre cada variável explicativa de interesse com sexo e idade para verificar a presença de modificação de efeito. Observamos que os maiores quintis de MM e BMC estiveram associados a um aumento na média da FPM em relação ao primeiro quintil, com maiores magnitudes em homens em relação a mulheres, também em adultos em relação a idosos. Quando estimamos o efeito independente de cada exposição de interesse, MM mostrou efeito mais forte na FPM em mulheres, homens e adultos do que BMC. Em conclusão, observamos que maiores quantidades de MM e BMC estão associadas a maior FPM, independentemente das características sociodemográficas, condições de saúde e estilo de vida, sendo esse efeito maior em homens e adultos.

Monoclonal antibodies for Alzheimer disease: statistical significance vs clinical efficacy / Anticorpos monoclonais para doença de Alzheimer: significância estatística versus eficácia clínica

Nas últimas décadas, os anticorpos monoclonais (AcM) promoveram uma transformação dramática no tratamento de diversas doenças, especialmente nos linfomas, leucemias, câncer de mama e câncer colorretal. Estima-se que atualmente as indústrias de biotecnologia ligadas ao desenvolvimento de AcM são responsáveis por importante fatia do produto interno bruto de muitos países onde essas indústrias estão sediadas. Já as pesquisas com AcM para doença de Alzheimer (DA) alicerçadas na hipótese da cascata amiloide parecem não apresentar os mesmos resultados. Alguns ensaios clínicos realizados com crenezumabe e solanezumabe não conseguiram demonstrar uma desaceleração da progressão clínica da doença, fazendo com que seus respectivos laboratórios encerrassem novos ensaios clínicos com essas drogas. Não obstante a falha de eficácia de alguns fármacos, outros recentes resultados de ensaios clínicos facilitaram a aprovação do aducanumabe pelo Food and Drug Administration (FDA) dos Estados Unidos (EUA) em junho de 2021, um anticorpo monoclonal IgG1 humano anti-beta amiloide (Aß) seletivo, como o primeiro tratamento modificador da doença na DA, especificamente para as fases de comprometimento cognitivo leve (CCL) e de demência leve. Dois anos após, o FDA também concedeu aprovação acelerada a outro AcM, o lecanemabe, e muito provavelmente o mesmo ocorrerá com o donanemabe após recente publicação do ensaio clínico TRAILBLAZER-ALZ 2.

In recent decades, monoclonal antibodies (MAbs) have dramatically shifted the treatment landscape for multiple malignant diseases, especially lymphomas and leukemias, breast cancer, and colorectal cancer. This change has been so momentous that many biotechnology companies involved in MAb discovery and development are currently estimated to account for a major share of the gross domestic product of their host countries. Research on MAb therapies for Alzheimer's disease (AD), however, all of which has been based on the amyloid cascade hypothesis, does not seem to have achieved similar results. Some clinical trials carried out with crenezumab and solanezumab failed to demonstrate slowing of clinical progression of AD, causing their respective manufacturers to discontinue further development. The lack of efficacy of these drugs notwithstanding, the recent results of clinical trials with another drug, aducanumab ­ a human IgG1 MAb which selectively targets aggregated amyloid-beta (Aß) ­ led to its FDA approval in June 2021 as the first ever disease-modifying treatment for AD, specifically at the mild cognitive impairment (MCI) and mild dementia stages. Two years later, the FDA granted accelerated approval to another MAb, lecanemab; a third, donanemab, is likely to follow, with the recent publication of the TRAILBLAZER-ALZ 2 trial.

Diagnóstico do comprometimento cognitivo vascular: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis of vascular cognitive impairment: recommendations of the scientific department of cognitive neurology and aging of the Brazilian Academy of Neurology

RESUMO Desde a publicação das últimas recomendações para o diagnóstico e tratamento da Demência Vascular pela Academia Brasileira de Neurologia em 2011, avanços significativos ocorreram na terminologia e critérios diagnósticos. O presente manuscrito é resultado do consenso entre especialistas indicados pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia (2020-2022). O objetivo foi atualizar as recomendações práticas para a identificação, classificação e diagnóstico do Comprometimento Cognitivo Vascular (CCV). As buscas foram realizadas nas plataformas MEDLINE, Scopus, Scielo e LILACS. As recomendações buscam fornecer uma ampla revisão sobre o tema, então sintetizar as evidências para o diagnóstico do CCV não apenas para neurologistas, mas também para outros profissionais de saúde envolvidos na avaliação e nos cuidados ao paciente com CCV, considerando as diferentes realidades dos níveis de atenção à saúde (primário, secundário e terciário) no Brasil.

ABSTRACT Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil.

Retest effects in a diverse sample: sociodemographic predictors and possible correction approaches / Efeito de reteste em uma amostra diversa: preditores sociodemográficos e possíveis abordagens para a correção

ABSTRACT. Repeated cognitive assessment in longitudinal studies favors the occurrence of retest effects, usually increasing the scores obtained at the follow-up assessments when compared to baseline. Therefore, retest effects can compromise the evaluation of cognitive decline in older adults. Objectives: We aimed to verify the occurrence of the retest effect and the impact of sociodemographic characteristics on the follow-up scores in a sample of 5,592 participants with a diverse sociodemographic profile, who were assessed twice during 4 years of follow-up. Methods: We tested two possible approaches to correct the retest effect and calculated the Reliable Change Index. Results: We observed increased scores at the follow-up assessment after 4 years, but the results indicate a modest occurrence of retest effects. The regression difference correction successfully generated follow-up corrected scores, while the mean difference did not provide effective corrections. Sociodemographic characteristics had a minor impact on the retest. Conclusions: We recommend the regression difference correction for retest effects. The absence of this methodological approach might lead to biased results using longitudinal cognitive scores.

RESUMO. Avaliações cognitivas repetidas em estudos longitudinais favorecem a ocorrência de efeitos de retestagem ou de prática, geralmente aumentando os escores obtidos nas avaliações de acompanhamento quando comparados aos da primeira avaliação. Sendo assim, os efeitos do retestagem podem comprometer a verificação do declínio cognitivo em idosos. Objetivos: Objetivamos verificar a ocorrência do efeito de prática e o impacto das características sociodemográficas nos escores de seguimento em uma amostra de 5.592 participantes com perfil sociodemográfico diverso, avaliada duas vezes durante quatro anos de seguimento. Métodos: Testamos duas abordagens possíveis para corrigir o efeito de prática e calculamos o índice de mudança confiável. Resultados: Observamos escores sutilmente maiores na avaliação de seguimento após quatro anos, o que sugere a ocorrência de efeitos de retestagem. A correção pela diferença da regressão gerou escores corrigidos de acompanhamento satisfatórios, enquanto a correção pela diferença média não forneceu correções eficazes. As características sociodemográficas tiveram impacto mínimo no efeito de prática. Conclusões: Recomendamos a forma de correção pela diferença da regressão para efeitos de retestagem. A ausência dessa abordagem metodológica, quando utilizamos escores cognitivos longitudinais, pode levar a resultados enviesados.

Microcephaly measurement in adults and its association with clinical variables

ABSTRACT OBJECTIVE To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.

The role of VES-13 to identify limited life expectancy in older adults in primary healthcare settings / O potencial do VES-13 na identificação da expectativa de vida limitada em idosos na atenção primária à saúde / Potencial del VES-13 para identificar la esperanza de vida limitada de adultos mayores en centros de atención primaria

ABSTRACT 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.

RESUMO 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.

RESUMEN Objetivo Investigar el potencial del instrumento Vulnerable Elders Survey para identificar adultos mayores con esperanza de vida limitada en centros de atención primaria. Método Se trata de un estudio transversal realizado en todas las (nueve) unidades sanitarias de Jataí, Goiás (Brasil) de julio a diciembre de 2018. Se consideró una población de ≥ 60 años, de la cual se obtuvo una muestra de 407 adultos mayores. Los participantes respondieron un cuestionario sobre características sociodemográficas y clínicas, incluyendo el Vulnerable Elders Survey y el índice de Suemoto. Se comprobó la asociación entre la esperanza de vida limitada y el Vulnerable Elders Survey, mediante el análisis de regresión logística múltiple. Resultados La edad promedio era de 68,9 ± 6,6 años y el 58,0% de los participantes pertenecía al sexo femenino. La puntuación media del Vulnerable Elders Survey resultó en 2,0 ± 2,2; la puntuación media del índice de Suemoto, 31,5 ± 21,1% y el 17,2% de los participantes tenía una esperanza de vida limitada. El Vulnerable Elders Survey estaba asociado a una esperanza de vida limitada (OR = 1,57; p = < 0,0001). Conclusión El instrumento Vulnerable Elders Survey ha sido capaz de identificar a los adultos mayores con una esperanza de vida limitada en los centros de atención primaria, además de ayudar en la detección de aquellos adultos mayores que no se beneficiarían con el triaje y el control estricto de las enfermedades crónicas.

Serum folate levels and cognitive performance in the ELSA-Brasil baseline assessment / Níveis séricos de folato e desempenho cognitivo na avaliação de linha de base do ELSA-Brasil

ABSTRACT Background: Most studies that analyze the association between serum folate levels and cognitive function either restrict their assessments to specific clinical scenarios or do not include middle-aged individuals, to whom strategies for preventing cognitive impairment may be more feasible. Objective: To examine the association between serum folate levels and cognitive function in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. Methods: Data from 4,571 ELSA-Brasil participants who live in the state of São Paulo, aged 35-74 years, were analyzed. The word list learning, delayed recall, word recognition, verbal fluency, and Trail Making Test Part B consisted in the cognitive tests. For each test, age, sex, and education-specific standardized scores and a global cognitive score were calculated. Crude and adjusted linear regression models were used to examine the associations of serum folate levels with cognitive test scores. Results: In multivariable-adjusted models, serum folate was not associated with global cognitive score (β=-0.043; 95% confidence interval [95%CI] -0.135 to 0.050 for lowest vs. highest quintile group), nor with any cognitive test performance. We did not find associations between serum folate and global cognitive scores in subgroups stratified by age, sex, or use of vitamin supplements either. Conclusions: We did not find significant associations between serum folate and cognitive performance in this large sample, which is characterized by a context of food fortification policies and a consequent low frequency of folate deficiency. Positive results from previous studies may not apply to the increasingly common contexts in which food fortification is implemented, or to younger individuals.

RESUMO Introdução: A maioria dos estudos que analisam a associação entre os níveis séricos de folato e a função cognitiva restringem suas avaliações a cenários clínicos específicos ou não incluem indivíduos de meia idade, nos quais estratégias preventivas para a função cognitiva podem ser mais viáveis. Objetivo: Examinar a associação entre os níveis séricos de folato e a função cognitiva na avaliação inicial do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). Métodos: Foram analisados dados de 4.571 participantes do ELSA-Brasil em São Paulo, com idades entre 35 e 74 anos. Os testes cognitivos foram aprendizagem, recordatório tardio e reconhecimento de lista de palavras; fluência verbal e teste de trilhas parte B. Calculamos, para cada teste e globalmente, escores padronizados para idade, sexo e educação. Foram utilizados modelos de regressão linear para examinar as associações dos níveis séricos de folato com o desempenho nos testes cognitivos. Resultados: Em modelos ajustados para múltiplas variáveis, o folato sérico não esteve associado ao escore cognitivo global (β=-0,043; intervalo de confiança de 95%: [IC95%] -0,135 a 0,050 para 1º vs. 5º quintil), ou desempenho em qualquer teste cognitivo. Também não encontramos associações entre folato sérico e escores cognitivos globais em subgrupos estratificados por idade, sexo ou uso de suplementos vitamínicos. Conclusões: Não encontramos associações significativas entre folato sérico e desempenho cognitivo nesta grande amostra, caracterizada por um cenário sob políticas de fortificação alimentar e consequente baixa frequência de deficiência de folato. Resultados positivos de estudos anteriores podem não se aplicar às situações cada vez mais comuns em que a fortificação de alimentos é implementada, ou a indivíduos mais jovens.

Hypertension is the underlying cause of death assessed at the autopsy of individuals / La hipertensión arterial es causa subyacente de muerte evaluada en la autopsia de individuos / A hipertensão arterial é causa subjacente de morte avaliada na autópsia de indivíduos

ABSTRACT 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.

RESUMEN 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.

RESUMO 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 diabetes and causes of dementia: Evidence from a clinicopathological study / Associação entre diabetes e causas de demência: evidência de um estudo clínico-patológico

ABSTRACT.Background: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia. Objective: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study. Methods: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression. Results: We included 1,037 subjects and diabetes was present in 279 participants (27%). The prevalence of dementia diagnosis was similar in diabetics (29%) and non-diabetics (27%). We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03). Conclusion: Diabetes was not associated with dementia in this large clinicopathological study.

RESUMO. Introdução: Diabetes mellitus é um fator de risco para a demência, especialmente para a demência vascular (DV), mas ainda não há consenso sobre diabetes como fator de risco para a doença de Alzheimer (DA) e outras causas de demência. Objetivo: Verificar a associação entre diabetes e demência e sua etiologia neuropatológica em um grande estudo de autópsia. Métodos: Os dados foram coletados do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral da FMUSP entre 2004 e 2015. O diagnóstico de diabetes foi relatado por pelos parentes do falecido. A demência clínica foi estabelecida quando CDR ≥ 1 e IQCODE > 3,41. A etiologia da demência foi determinada pelo exame neuropatológico com imuno-histoquímica. A associação de diabetes com probabilidades de demência foi investigada usando regressão logística multivariada. Resultados: Foram incluídos 1.037 sujeitos, diabetes esteve presente em 279 participantes (27%). A frequência de diagnóstico de demência foi semelhante entre diabéticos (29%) e não diabéticos (27%). Não encontramos associação entre diabetes e demência (OR = 1,22; IC 95% = 0,81-1,82; p = 0,34) na análise multivariada. DA foi a principal causa de demência em ambos os grupos, DV foi a segunda causa em diabéticos. A frequência de outra demência mista foi a segunda causa de demência e mais frequente entre os não diabéticos (p = 0,03). Conclusão: A diabetes não foi associada à demência neste grande estudo clínico-patológico.