Clinical and functional correlates of parkinsonism in a population-based sample of individuals aged 75 + : the Pietà study.

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.

Machine Learning-Based Routine Laboratory Tests Predict One-Year Cognitive and Functional Decline in a Population Aged 75+ Years.

BACKGROUND: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study. METHOD: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features. RESULTS: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92). CONCLUSIONS: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.

Social cognition across bipolar disorder and behavioral-variant frontotemporal dementia: an exploratory study

Objectives: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. Methods: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. Results: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). Conclusion: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.

High performance older adults in a population-based sample with low education: Pietà study.

BACKGROUND: Healthy brain aging can be defined as aging without neurological or psychiatric disorders, sustaining functional independence. In addition to the absence of disease and preserved functionality, there are individuals who stand out for their superior performance to that considered normal for their age in cognitive tests. These individuals are called "high-performance older adults" (HPOA). OBJECTIVES: To investigate the presence of HPOA in an oldest-old population with low education, and if present, to investigate associations with sociodemographic, clinical, and lifestyle variables. METHODS: We evaluated 132 cognitively healthy individuals from the Pietà Study, a population-based investigation with 639 participants. We used the delayed recall from the Rey Auditory-Verbal Learning Test to verify the existence of HPOA and to classify participants based on their performance. Sociodemographic, clinical, and lifestyle variables associated with HPOA were investigated. RESULTS: We identified 18 individuals fulfilling HPOA criteria (age: 77.4 ± 2.6 years old; 14 women; education: 4.6 ± 3.4 years). The other participants, 114 total (age: 79.8 ± 4.5 years old; 69 women; education: 3.0 ± 2.7 years) were classified as "standard performance older adults" (SPOA). In multivariate analysis, younger age (odds ratio [OR] = 0.672; 95% confidence interval [CI]: 0.462-0.979; p = 0.037) and lower scores on the Geriatric Depression Scale (OR = 0.831; 95%CI: 0.688-0.989; p = 0.038) were associated with HPOA. CONCLUSIONS: The present study identifies for the first time HPOA with low educational level, thereby reinforcing the existence of biological substrates related to this condition. Furthermore, the data suggest an association between younger age and less depressive symptoms with HPOA.

ANTECEDENTES: Envelhecimento cerebral saudável pode ser definido como envelhecimento sem transtornos neurológicos ou psiquiátricos e com independência funcional. Além da ausência de doença e funcionalidade preservada, existem indivíduos que se destacam pelo desempenho superior ao normal em testes cognitivos. Estes indivíduos são chamados de "high performance older adults" (HPOA, na sigla em inglês). OBJETIVOS: Investigar a presença de HPOA em uma população de idosos com baixa escolaridade e, se presente, investigar associações com variáveis sociodemográficas, clínicas e de estilo de vida. MéTODOS: Avaliamos 132 indivíduos cognitivamente saudáveis do Estudo Pietà (n = 639). Foi utilizado o Teste de Aprendizagem Auditivo-Verbal de Rey para verificar a existência de HPOA e classificar os participantes em dois grupos com base em seu desempenho. Variáveis sociodemográficas, clínicas e de estilo de vida associadas a HPOA foram investigadas. RESULTADOS: Identificamos 18 indivíduos que preencheram critérios para HPOA (idade: 77,4 ± 2,6 anos; 14 mulheres; escolaridade: 4,6 ± 3,4 anos). Os demais, 114 no total (idade: 79,8 ± 4,5 anos; 69 mulheres; escolaridade: 3,0 ± 2,7 anos), foram classificados como "standard performance older adults" (SPOA, na sigla em inglês). Na análise multivariada, menor idade (odds ratio [OR] = 0,672; intervalo de confiança [IC] 95%: 0,462­0,979; p = 0,037) e menor pontuação na Escala de Depressão Geriátrica (OR = 0,831; IC95%: 0,688­0,989; p = 0,038) foram associados ao grupo HPOA. CONCLUSõES: O presente estudo identifica pela primeira vez HPOA entre indivíduos de baixa escolaridade, reforçando a existência de substratos biológicos relacionados a esta condição. Além disso, os dados sugerem uma associação entre idade mais jovem e menos sintomas depressivos com HPOA.

Social cognition across bipolar disorder and behavioral variant frontotemporal dementia: an exploratory study.

OBJECTIVES: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. METHODS: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. RESULTS: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). CONCLUSION: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.

High performance older adults in a population-based sample with low education: Pietà study / Idosos de alta performance cognitiva em uma amostra de base populacional com baixa escolaridade: estudo Pietà

Abstract Background Healthy brain aging can be defined as aging without neurological or psychiatric disorders, sustaining functional independence. In addition to the absence of disease and preserved functionality, there are individuals who stand out for their superior performance to that considered normal for their age in cognitive tests. These individuals are called "high-performance older adults" (HPOA). Objectives To investigate the presence of HPOA in an oldest-old population with low education, and if present, to investigate associations with sociodemographic, clinical, and lifestyle variables. Methods We evaluated 132 cognitively healthy individuals from the Pietà Study, a population-based investigation with 639 participants. We used the delayed recall from the Rey Auditory-Verbal Learning Test to verify the existence of HPOA and to classify participants based on their performance. Sociodemographic, clinical, and lifestyle variables associated with HPOA were investigated. Results We identified 18 individuals fulfilling HPOA criteria (age: 77.4 ± 2.6 years old; 14 women; education: 4.6 ± 3.4 years). The other participants, 114 total (age: 79.8 ± 4.5 years old; 69 women; education: 3.0 ± 2.7 years) were classified as "standard performance older adults" (SPOA). In multivariate analysis, younger age (odds ratio [OR] =0.672; 95% confidence interval [CI]: 0.462-0.979; p = 0.037) and lower scores on the Geriatric Depression Scale (OR = 0.831; 95%CI: 0.688-0.989; p = 0.038) were associated with HPOA. Conclusions The present study identifies for the first time HPOA with low educational level, thereby reinforcing the existence of biological substrates related to this condition. Furthermore, the data suggest an association between younger age and less depressive symptoms with HPOA.

Resumo Antecedentes Envelhecimento cerebral saudável pode ser definido como envelhecimento sem transtornos neurológicos ou psiquiátricos e com independência funcional. Além da ausência de doença e funcionalidade preservada, existem indivíduos que se destacam pelo desempenho superior ao normal em testes cognitivos. Estes indivíduos são chamados de "high performance older adults" (HPOA, na sigla em inglês). Objetivos Investigar a presença de HPOA em uma população de idosos com baixa escolaridade e, se presente, investigar associações com variáveis sociodemográficas, clínicas e de estilo de vida. Métodos Avaliamos 132 indivíduos cognitivamente saudáveis do Estudo Pietà (n = 639). Foi utilizado o Teste de Aprendizagem Auditivo-Verbal de Rey para verificar a existência de HPOA e classificar os participantes em dois grupos com base em seu desempenho. Variáveis sociodemográficas, clínicas e de estilo de vida associadas a HPOA foram investigadas. Resultados Identificamos 18 indivíduos que preencheram critérios para HPOA (idade: 77,4 ± 2,6 anos; 14 mulheres; escolaridade: 4,6 ± 3,4 anos). Os demais, 114 no total (idade: 79,8 ± 4,5 anos; 69 mulheres; escolaridade: 3,0 ± 2,7 anos), foram classificados como "standard performance older adults" (SPOA, na sigla em inglês). Na análise multivariada, menor idade (odds ratio [OR] =0,672; intervalo de confiança [IC] 95%: 0,462-0,979; p = 0,037) e menor pontuação na Escala de Depressão Geriátrica (OR = 0,831; IC95%: 0,688-0,989; p = 0,038) foram associados ao grupo HPOA. Conclusões O presente estudo identifica pela primeira vez HPOA entre indivíduos de baixa escolaridade, reforçando a existência de substratos biológicos relacionados a esta condição. Além disso, os dados sugerem uma associação entre idade mais jovem e menos sintomas depressivos com HPOA.

Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19.

Purpose: The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19. Methods: The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured. Results: In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853-11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215-7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = -0.500), cardiac troponin (r = -1.00), IL-6 (r = -1.00), and IL-10 (r = -1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = -0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700). Conclusion: In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.

I'm looking through you: Mentalizing in frontotemporal dementia and progressive supranuclear palsy.

Mentalizing and emotion recognition are impaired in behavioral variant frontotemporal dementia (bvFTD). It is not clear whether these abilities are also disturbed in other conditions with prominent frontal lobe involvement, such as progressive supranuclear palsy (PSP). Our aim was to investigate social cognition (facial emotion recognition, recognition of social norms violation and mentalizing) in bvFTD and PSP. The neural basis of these functions in PSP and bvFTD groups, by analysis of structural neuroimaging, were also investigated. Twenty-three bvFTD patients, 21 PSP patients and 23 healthy controls were included. All participants underwent 3T brain MRI and a full cognitive exam including the short version of Social and Emotional Assessment (Mini-SEA), which is composed of a facial emotion recognition test (FERT) and the faux pas test. Two components of the faux pas test were distinguished: a score assessing the recognition of social norms violation and a score assessing mentalizing. Compared to controls, bvFTD and PSP patients had significantly reduced scores in all tests of social cognition but did not differ on these measures. PSP and bvFTD had cerebral atrophy in critical regions for social cognition processes, when compared to controls. The cortical correlates of emotion recognition partially overlapped in bvFTD and PSP, with correlations retrieved within the frontal medial cortex, cingulate, insula and limbic structures. PSP and bvFTD patients also displayed similar patterns of brain correlations for the composite score of social norms, with a significant cluster in anterior temporal lobes. Mentalizing scores were associated with frontal and temporal poles bilaterally, in both bvFTD and PSP. These findings support previous observations that PSP patients exhibit impairment in complex cognitive abilities, such as mentalizing. Moreover, these data extend previous findings showing that PSP and bvFTD share key clinical, cognitive and neuroimaging features.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

Hospital characteristics associated with COVID-19 mortality: data from the multicenter cohort Brazilian Registry.

The COVID-19 pandemic caused unprecedented pressure over health care systems worldwide. Hospital-level data that may influence the prognosis in COVID-19 patients still needs to be better investigated. Therefore, this study analyzed regional socioeconomic, hospital, and intensive care units (ICU) characteristics associated with in-hospital mortality in COVID-19 patients admitted to Brazilian institutions. This multicenter retrospective cohort study is part of the Brazilian COVID-19 Registry. We enrolled patients ≥ 18 years old with laboratory-confirmed COVID-19 admitted to the participating hospitals from March to September 2020. Patients' data were obtained through hospital records. Hospitals' data were collected through forms filled in loco and through open national databases. Generalized linear mixed models with logit link function were used for pooling mortality and to assess the association between hospital characteristics and mortality estimates. We built two models, one tested general hospital characteristics while the other tested ICU characteristics. All analyses were adjusted for the proportion of high-risk patients at admission. Thirty-one hospitals were included. The mean number of beds was 320.4 ± 186.6. These hospitals had eligible 6556 COVID-19 admissions during the study period. Estimated in-hospital mortality ranged from 9.0 to 48.0%. The first model included all 31 hospitals and showed that a private source of funding (ß = - 0.37; 95% CI - 0.71 to - 0.04; p = 0.029) and location in areas with a high gross domestic product (GDP) per capita (ß = - 0.40; 95% CI - 0.72 to - 0.08; p = 0.014) were independently associated with a lower mortality. The second model included 23 hospitals and showed that hospitals with an ICU work shift composed of more than 50% of intensivists (ß = - 0.59; 95% CI - 0.98 to - 0.20; p = 0.003) had lower mortality while hospitals with a higher proportion of less experienced medical professionals had higher mortality (ß = 0.40; 95% CI 0.11-0.68; p = 0.006). The impact of those association increased according to the proportion of high-risk patients at admission. In-hospital mortality varied significantly among Brazilian hospitals. Private-funded hospitals and those located in municipalities with a high GDP had a lower mortality. When analyzing ICU-specific characteristics, hospitals with more experienced ICU teams had a reduced mortality.

Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study.

BACKGROUND: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19. METHODS: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored. RESULTS: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups. CONCLUSION: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed.

Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.

BACKGROUND: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS: Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION: Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.

Brazilian Version of Addenbrooke's Cognitive Examination-Revised in the Differential Diagnosis of Alzheimer'S Disease and Behavioral Variant Frontotemporal Dementia.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are frequent causes of dementia and, therefore, instruments for differential diagnosis between these two conditions are of great relevance. OBJECTIVE: To investigate the diagnostic accuracy of Addenbrooke's Cognitive Examination-Revised (ACE-R) for differentiating AD from bvFTD in a Brazilian sample. METHODS: The ACE-R was administered to 102 patients who had been diagnosed with mild dementia due to probable AD, 37 with mild bvFTD and 161 cognitively healthy controls, matched according to age and education. Additionally, all subjects were assessed using the Mattis Dementia Rating Scale and the Neuropsychiatric Inventory. The performance of patients and controls was compared by using univariate analysis, and ROC curves were calculated to investigate the accuracy of ACE-R for differentiating AD from bvFTD and for differentiating AD and bvFTD from controls. The verbal fluency plus language to orientation plus name and address delayed recall memory (VLOM) ratio was also calculated. RESULTS: The optimum cutoff scores for ACE-R were <80 for AD, <79 for bvFTD, and <80 for dementia (AD + bvFTD), with area under the receiver operating characteristic curves (ROC) (AUC) >0.85. For the differential diagnosis between AD and bvFTD, a VLOM ratio of 3.05 showed an AUC of 0.816 (Cohen's d = 1.151; p < .001), with 86.5% sensitivity, 71.4% specificity, 72.7% positive predictive value, and 85.7% negative predictive value. CONCLUSIONS: The Brazilian ACE-R achieved a good diagnostic accuracy for differentiating AD from bvFTD patients and for differentiating AD and bvFTD from the controls in the present sample.

Treatment of the behavioral variant of frontotemporal dementia: a narrative review.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder accompanied by behavioral and personality changes and/or language deterioration. Its behavioral variant (bvFTD) is the main clinical presentation. OBJECTIVE: This study aims to investigate the treatment alternatives for bvFTD available so far. METHODS: We conducted a narrative review of bvFTD treatment options. We used PubMed and Lilacs databases with the terms "frontotemporal dementia" or "behavioral variant frontotemporal dementia" combined with "treatment," "pharmacological treatment," or "disease-modifying drugs." RESULTS: The articles retrieved and selected in the research pointed out that there is no specific treatment approved for bvFTD so far. The current proposals are limited to handle the cardinal behavioral symptoms of the disorder. Disease-modifying drugs are under development and may be promising, especially in the monogenic presentations of FTD. CONCLUSIONS: There are numerous approaches to treat the core symptoms of bvFTD, most of them based on low-quality research. To date, there are no drugs with a disease-specific therapeutic recommendation for bvFTD. Treatments are often investigated guided by primary psychiatric disorders with similar symptoms and should be chosen by the predominant symptom profile.

A demência frontotemporal (DFT) é um transtorno neurodegenerativo progressivo acompanhado de deterioração do comportamento e da personalidade e/ou da linguagem. A variante comportamental (DFTvc) é a principal apresentação clínica. OBJETIVOS: Investigar as alternativas de tratamento disponíveis para a DFTvc até o momento. MÉTODOS: Realizou-se uma revisão narrativa das opções de tratamento da DFTvc. Os bancos de dados PubMed e Lilacs foram utilizados com os termos "demência frontotemporal" ou "variante comportamental da demência frontotemporal" combinados com "tratamento", "tratamento farmacológico" ou "drogas modificadoras de doença". RESULTADOS: Os artigos recuperados e selecionados na pesquisa indicaram que não há nenhum tratamento específico aprovado até o momento para DFTvc. As propostas atuais são limitadas ao tratamento dos sintomas comportamentais cardinais do transtorno. As drogas modificadoras de doença estão em desenvolvimento e podem ser promissoras, especialmente nas apresentações monogênicas da DFT. CONCLUSÕES: Há inúmeras abordagens para tratar os principais sintomas DFTvc, a maioria delas baseada em pesquisas de baixa qualidade. Até o momento, não existem medicamentos com uma recomendação terapêutica específica para a DFTvc. Os tratamentos são frequentemente investigados guiados por distúrbios psiquiátricos primários com sintomas semelhantes e devem ser escolhidos pelo perfil de sintomas predominante.

Chagas disease and SARS-CoV-2 coinfection does not lead to worse in-hospital outcomes.

Chagas disease (CD) continues to be a major public health burden in Latina America. Information on the interplay between COVID-19 and CD is lacking. Our aim was to assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients. Consecutive patients with confirmed COVID-19 were included from March to September 2020. Genetic matching for sex, age, hypertension, diabetes mellitus and hospital was performed in a 4:1 ratio. Of the 7018 patients who had confirmed COVID-19, 31 patients with CD and 124 matched controls were included (median age 72 (64-80) years-old, 44.5% were male). At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (p < 0.05). C-reactive protein levels were lower in CD patients compared with the controls (55.5 [35.7, 85.0] vs. 94.3 [50.7, 167.5] mg/dL). In-hospital management, outcomes and complications were similar between the groups. In this large Brazilian COVID-19 Registry, CD patients had a higher prevalence of atrial fibrillation and chronic heart failure compared with non-CD controls, with no differences in-hospital outcomes. The lower C-reactive protein levels in CD patients require further investigation.

Neuropsychiatric Symptoms in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease: A 12-Month Follow-Up Study.

Introduction: Neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical managements. Objective: To test whether the Neuropsychiatry Inventory (NPI) could detect change in neuropsychiatric symptoms and caregiver's distress in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) from baseline to a 12-month follow-up and to investigate possible predictors of change in NPI scores. Methods: The sample consisted of 31 patients diagnosed with bvFTD and 28 patients with AD and their caregivers. The Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), the INECO Frontal Screening (IFS), the Frontal Assessment Battery (FAB), the Executive Interview (EXIT-25) and the NPI were applied. Descriptive statistics, Mann-Whitney U test, Wilcoxon test, Chi square (χ2) test and Linear Regression Analysis were used. Results: NPI total and caregiver distress scores were statistically higher among bvFTD patients at both assessment points. MMSE, ACE-R scores significantly declined and NPI Total and Distress scores significantly increased in both groups. In the bvFTD group, age was the only independent predictor variable for the NPI total score at follow up. In the AD group, ACE-R and EXIT-25, conjunctively, were associated with the NPI total score at follow up. Conclusions: In 12 months, cognition declined and neuropsychiatric symptoms increased in bvFTD and AD groups. In the AD group only, cognitive impairment was a significant predictor of change in neuropsychiatric symptoms.

Treatment of the behavioral variant of frontotemporal dementia: a narrative review / Tratamento da variante comportamental da demência frontotemporal: uma revisão narrativa

ABSTRACT Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder accompanied by behavioral and personality changes and/or language deterioration. Its behavioral variant (bvFTD) is the main clinical presentation. Objective: This study aims to investigate the treatment alternatives for bvFTD available so far. Methods: We conducted a narrative review of bvFTD treatment options. We used PubMed and Lilacs databases with the terms "frontotemporal dementia" or "behavioral variant frontotemporal dementia" combined with "treatment," "pharmacological treatment," or "disease-modifying drugs." Results: The articles retrieved and selected in the research pointed out that there is no specific treatment approved for bvFTD so far. The current proposals are limited to handle the cardinal behavioral symptoms of the disorder. Disease-modifying drugs are under development and may be promising, especially in the monogenic presentations of FTD. Conclusions: There are numerous approaches to treat the core symptoms of bvFTD, most of them based on low-quality research. To date, there are no drugs with a disease-specific therapeutic recommendation for bvFTD. Treatments are often investigated guided by primary psychiatric disorders with similar symptoms and should be chosen by the predominant symptom profile.

RESUMO A demência frontotemporal (DFT) é um transtorno neurodegenerativo progressivo acompanhado de deterioração do comportamento e da personalidade e/ou da linguagem. A variante comportamental (DFTvc) é a principal apresentação clínica. Objetivos: Investigar as alternativas de tratamento disponíveis para a DFTvc até o momento. Métodos: Realizou-se uma revisão narrativa das opções de tratamento da DFTvc. Os bancos de dados PubMed e Lilacs foram utilizados com os termos "demência frontotemporal" ou "variante comportamental da demência frontotemporal" combinados com "tratamento", "tratamento farmacológico" ou "drogas modificadoras de doença". Resultados: Os artigos recuperados e selecionados na pesquisa indicaram que não há nenhum tratamento específico aprovado até o momento para DFTvc. As propostas atuais são limitadas ao tratamento dos sintomas comportamentais cardinais do transtorno. As drogas modificadoras de doença estão em desenvolvimento e podem ser promissoras, especialmente nas apresentações monogênicas da DFT. Conclusões: Há inúmeras abordagens para tratar os principais sintomas DFTvc, a maioria delas baseada em pesquisas de baixa qualidade. Até o momento, não existem medicamentos com uma recomendação terapêutica específica para a DFTvc. Os tratamentos são frequentemente investigados guiados por distúrbios psiquiátricos primários com sintomas semelhantes e devem ser escolhidos pelo perfil de sintomas predominante.

Different patterns of gray matter atrophy in behavioral variant frontotemporal dementia with and without episodic memory impairment.

BACKGROUND: Differentiating patients with behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) is important as these two conditions have distinct treatment and prognosis. Using episodic impairment and medial temporal lobe atrophy as a tool to make this distinction has been debatable in the recent literature, as some patients with bvFTD can also have episodic memory impairment and medial temporal lobe atrophy early in the disease. OBJECTIVES: To compare brain atrophy patterns of patients with bvFTD with and without episodic memory impairment to that of patients with AD. METHODS: We analyzed 19 patients with bvFTD, 21 with AD and 21 controls, matched by age, sex, and years of education. They underwent brain MRI and the memory test from the Brief Cognitive Battery (BCB) to assess episodic memory. We then categorized the bvFTD group into amnestic (BCB delayed recall score <7) and non-amnestic. RESULTS: The amnestic bvFTD group (n = 8) had significant gray matter atrophy in the left parahippocampal gyrus, right cingulate and precuneus regions compared with the nonamnestic group. Compared with AD, amnestic bvFTD had more atrophy in the left fusiform cortex, left insula, left inferior temporal gyrus and right temporal pole, whereas patients with AD had more atrophy in the left hippocampus, left frontal pole and left angular gyrus. CONCLUSIONS: There is a group of amnestic bvFTD patients with episodic memory dysfunction and significant atrophy in medial temporal structures, which poses a challenge in considering only these features when differentiating bvFTD from AD clinically.

Diabetes and impaired fasting glucose in a population-based sample of individuals aged 75 + years: associations with cognition, major depressive disorder, functionality and quality of life-the Pietà study.

OBJECTIVES: To investigate the rates of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a population-based sample of individuals aged 75 + years old and their associations with cognitive performance, depression, functionality, and quality of life (QoL). STUDY DESIGN: Overall, 350 people participated in the study. Assessments of cognition, mood, functionality and QoL were performed using the mini-mental state examination (MMSE), clock-drawing, category fluency tests, the Mini-International Neuropsychiatric Interview, Pfeffer's Functional Activities Questionnaire, and the WHO Quality of Life-Old (WHOQOL-OLD). RESULTS: IFG (ADA criteria) was identified in 42.1% of the sample, while the DM rate was 24.1%. Lack of knowledge of the DM diagnosis and lack of treatment occurred in 27% and 39% of the sample, respectively. Rates of dementia and depression, MMSE, category fluency scores, and previous cardiovascular events did not differ between the glycaemic groups. Individuals with DM performed worse on the clock-drawing test, functionality, and WHOQOL-OLD than the other participants. Individuals with IFG presented similar QoL and functionality when compared with the group without DM. CONCLUSIONS: IFG and DM were common in this population-based sample aged 75 + years old, as were inadequate diagnoses and treatments of DM. DM individuals presented poor performance in the executive function test, functionality, and QoL. Further studies are recommended to investigate the value of an IFG diagnosis among the most elderly population.