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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oliveira, Caetano, Godoy, Oliveira, Melo Mambrini, Rezende, Fantini, Oliveira Mendes, Medeiros, Guimarães, Fiuza and Gaze.)

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., (© 2023. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest.

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.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors., (© 2023. The Author(s).)

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., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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., (© 2022. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2021. The Author(s).)

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 (χ 2 ) 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Da Silva, Ordonez, Bregola, Bahia, Cecchini, Guimarães, Gambogi, Caramelli, Balthazar, Damasceno, Brucki, de Souza, Nitrini and Yassuda.)

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones., Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients., Results: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO 2 /FiO 2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/)., Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objectives: To explore the relationship between severe/serious mental illness (SMI) and the behavioral variant of frontotemporal dementia (bvFTD), as the patterns of symptoms and cognitive performance that characterize both disorders share similarities., Methods: We performed a systematic review investigating what has already been published regarding the relationship between bvFTD and SMI. Studies were selected from PubMed and LILACS databases, including those published up to February 12, 2018. The search strategy included the following terms: "frontotemporal dementia" plus "bipolar", OR "frontotemporal dementia" plus "schizophrenia", OR "frontotemporal dementia" plus "schizoaffective". Publications without abstracts, case reports with absent genetic or histopathological confirmation, reviews and non-English language papers were excluded across the search process., Results: The search on PubMed retrieved 186 articles, of which 42 met eligibility criteria. On the LILACS database, none met the requirements. Generally, three major research aims were identified: 1) to look for frontotemporal lobar degeneration-associated genetic abnormalities in patients with prior SMI; 2) to compare the cognitive profile between patients affected by neurodegenerative disorders and schizophrenic patients; 3) to highlight the association between bvFTD and preceding psychiatric conditions and/or distinguish them both. The investigated mutations were found infrequently in the studied SMI samples. Cross-sectional studies comparing cognitive performance between bvFTD and psychiatric disorders mostly found no remarkable differences. There were only a few case reports identifying definite frontotemporal lobar degeneration in patients with previous psychiatric diagnoses., Conclusions: The available evidence demonstrates how fragile the current understanding is regarding the association between bvFTD and prior SMI.

Background: The phenocopy syndrome of behavioral variant of frontotemporal dementia (phFTD) refers to patients presenting with neuropsychiatric symptoms mimicking the behavioral variant frontotemporal dementia (bvFTD), but lacking frontotemporal atrophy/hypometabolism on neuroimaging and not evolving to dementia during the follow-up. It is important to recognize phFTD for clinical and research purposes., Objective: The aim of this study was to perform a systematic review of the available literature on phFTD taking into account its clinical, cognitive, imaging, genetic, and pathological features., Methods and Results: We searched for the following terms in two electronic databases (PubMed and Scopus): "frontotemporal dementia and slowly progressive," "frontotemporal dementia and phenocopy," "frontotemporal dementia and non-progressive," "frontotemporal dementia and benign progression," and "frontotemporal dementia and benign." We did not include review articles. Papers had to be written in English, French, Portuguese, or Spanish. Overall, 235 studies were retrieved in the initial search. A total of 31 studies composed the final selection, comprising 292 patients. Patients with phFTD are predominantly male and have no major cognitive deficits, with globally preserved executive functions and episodic memory. Some cases (n = 7) of slowly progressive FTD have been associated with C9orf72 genetic expansion. There are only four reports of phFTD neuropathological data, with two patients with no neurodegenerative findings and two with frontotemporal lobar degeneration with ubiquitin-positive inclusions., Conclusion: The neurobiological underpinnings of phFTD remain unknown. It is controversial whether phFTD belongs to the FTD spectrum. Studies with biomarkers and pathological data are needed to solve the phFTD conundrum.

According to the cognitive reserve theory, intellectual stimuli acquired during life can prevent against developing cognitive impairment. The underlying cognitive reserve mechanisms were underexplored in low-educated individuals. Because episodic memory impairment due to hippocampal dysfunction is a key feature of Alzheimer's dementia (AD), we sought to look at a possible cognitive reserve mechanism by determining whether few years of education moderated the relationship between the hippocampal volumes and the episodic-memory scores. The sample was composed by 183 older adults, 40.1% male, with the median age of 78[76,82] years and the median years of education of 4[2,10] who had undergone an episodic-memory test and a 3-Tesla MRI scan to access the hippocampal volumes. Overall, 112 were cognitively healthy, 26 had cognitive impairment-no dementia (CIND) and 45 had dementia. We used multiple linear regression to assess whether the interaction between years of education and each hippocampal volume significantly predicted the episodic-memory scores' variance, controlling for cognitive diagnosis and nuisance variables. The interaction term with the left hippocampus (ß = 0.2, p = 0.043, CI = 1.0, 1.4), but not with the right (ß = 0.1, p = 0.218, CI = 0.9, 1.2) significantly predicted the variation on memory scores. The mechanism by which the left hippocampus seems to play a more important role on memory processing in more educated individuals needs to be further investigated and might be associated with a better use of mnemonic strategies or higher hippocampal connectivity. Because the sample's median years of education was four, which corresponds to primary school, we may infer that this level might be sufficient to contribute for building cognitive reserve.

Objective: Elderly people are at a high risk of developing vitamin D (VitD) deficiency due to both decreased intake and cutaneous synthesis. Most of the biological actions of VitD are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, and in the cortex and subcortical nuclei, essential areas for cognition. It is known that VDR gene polymorphisms may decrease the VDR affinity for VitD. Objective: The present study aimed to investigate the influence of VitD levels on cognitive decline in patients with dementia due to Alzheimer's disease (AD, n = 32) and mild cognitive impairment (MCI, n = 15) compared to cognitively healthy elderly (n = 24)., Methods: We also evaluated the association of VDR gene polymorphisms with cognitive disturbance. Methods: Four polymorphisms on the VDR gene were studied, namely, BsmI, ApaI, FokI and TaqI, by polymerase chain reaction-restriction fragment length polymorphism. Serum levels of 25-hydroxy vitamin D (25(OH)D) were determined by high performance liquid chromatography., Results: Results: No significant difference in 25(OH)D levels or genotypic/allelic frequencies was observed between the groups. Deficiency of 25(OH)D was more frequently observed in women. The AA/AG genotypes of the BsmI polymorphism was associated with sufficient 25(OH)D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in the cognitively-impaired group (individuals with AD or MCI)., Conclusions: Conclusions: The data obtained do not confirm the relationship between reductions of VitD levels, polymorphisms in the VDR gene, and altered cognitive function in this sample. However, the data indicate that BsmI polymorphism in the VDR gene is associated with the VitD levels in individuals with cognitive decline.

The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease., Methods: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters., Results: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally., Conclusions: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

Introduction: Late-life depression (LLD) is common, but remains underdiagnosed. Validated screening tools for use with the oldest-old in clinical practice are still lacking, particularly in developing countries., Objectives: To evaluate the accuracy of a screening tool for LLD in a community-dwelling oldest-old sample., Methods: We evaluated 457 community-dwelling elderly subjects, aged ≥75 years and without dementia, with the Geriatric Depression Scale (GDS-15). Depression diagnosis was established according to DSM-IV criteria following a structured psychiatric interview with the Mini International Neuropsychiatric Interview (MINI)., Results: Fifty-two individuals (11.4%) were diagnosed with major depression. The area under the receiver operating characteristic (ROC) curve was 0.908 (p<0.001). Using a cut-off score of 5/6 (not depressed/depressed), 84 (18.4%) subjects were considered depressed by the GDS-15 (kappa coefficient = 53.8%, p<0.001). The 4/5 cut-off point achieved the best combination of sensitivity (86.5%) and specificity (82.7%) (Youden's index = 0.692), with robust negative (0.9802) and reasonable positive predictive values (0.3819)., Conclusion: GDS-15 showed good accuracy as a screening tool for major depression in this community-based sample of low-educated oldest-old individuals. Our findings support the use of the 4/5 cut-off score, which showed the best diagnostic capacity.

Methods: The individuals were categorized in two groups according to the presence or absence of cognitive decline. Cognitive data were related to genetic information., Results: The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement., Conclusion: These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging.

In developing countries, cardiovascular risk factors are poorly controlled, leading to high prevalence of cerebrovascular diseases. The aim of the study was to evaluate the burden of white matter lesions in magnetic resonance through the Fazekas scale in a population aged 75 + years living in the community, and to investigate possible associations between vascular lesions, cardiovascular risk factors and cognitive status. Subjects were selected from a community-based study on brain aging conducted in Caeté (Minas Gerais state), Brazil. Overall, 177 participants (112 cognitively healthy, 36 with cognitive impairment-no dementia and 29 with dementia), being 108 women, aged 79.3 ± 3.8 years, with 3.1 ± 2.9 years of educational level, underwent a 3 Tesla magnetic resonance scanner with fluid attenuated image recovery acquisition. Severity of white matter lesions was assessed through the Fazekas scale. Severe white matter lesions were present in 31.1% of the whole sample and in 25.0% of the cognitively healthy individuals. A significant association was found between severe white matter lesions and cognitive impairment (OR = 2.20, 95% CI 1.17-6.53; p = 0.021), as well as with hypertension (OR = 1.92, 95% CI 1.03-7.39; p = 0.043). In conclusion, a high prevalence of severe white matter lesions was observed in this elderly Brazilian population sample, and white matter lesions were associated with hypertension and cognitive status. Importantly, the prevalence of white matter lesions was also high in cognitively healthy subjects.

Background: Population aging is a global phenomenon whose main consequence is the increase of chronic degenerative diseases, including dementia. The aim of this case-control study was to evaluate the laboratorial parameters lipid profile, cortisol, and apolipoprotein E (APOE) gene genotype, comparing cognitively healthy controls and subjects with cognitive impairment no dementia (CIND) and dementia in a group of elderly people., Methods: Three hundred and nine individuals enrolled in the Pietà Study (Brazil) were divided into three groups: control (n = 158), CIND (n = 92), and dementia (n = 59). Participants were interviewed, went through examination, and had blood samples taken., Results: Age and APOE showed significant differences among the groups, while sex and lipid profile did not. According to multivariate regression logistic analyses, higher cortisol levels, lower high-density lipoprotein (HDL-c) and very low-density lipoprotein (VLDL-c), presence of ε4 allele of APOE, and aging were associated with CIND and dementia., Conclusion: These laboratorial parameters are risk factors associated to CIND and dementia in the elderly people and should be investigated in order to develop strategies to prevent or delay the onset of dementia in the oldest-old populations., (© 2015 Wiley Periodicals, Inc.)

Chronic mania is an under-investigated condition and few reports have associated this disorder with an organic background. The present work examines Kraepelin's reliable description of chronic mania from a current behavioral neurology viewpoint. Kraepelin had described a cluster of symptoms that are now recognized as core manifestations of the behavioral variant frontotemporal dementia (bvFTD) clinical phenotype. We also carried out additional reviews of original manuscripts from Kraepelin's peers, in order to find any case reports that might fulfill the current diagnostic proposal for bvFTD. Even though we failed to find an ideal case, we found some scholars who seemed to agree that chronic mania should be considered a special form of dementia. The present work highlights, through historical data, the possible overlapping features between primary psychiatric disorders and neuropsychiatric symptoms secondary to neurodegenerative conditions.

Objective: : To investigate the influence of patients' age on the delay between diagnosis and surgical treatment of proximal femoral fractures., Methods: : This is a retrospective study, con-ducted at a tertiary university hospital, including all patients admitted with proximal femoral fractures between March 2013 and March 2014. The participants were categorized into four groups according to age levels. The groups were compared according to demographics, comorbidities, fracture type, trau-ma circumstances, and time between diagnosis and surgical procedure., Results: : One hundred and sixty one patients were included, 37 adults and 124 elderly. Among adults, the mean delay between diagnosis and surgical procedure was 6.4±5.3 days; among elderly the delay was 9.5±7.6 days. There was a progressive increase in the delay from the young-adults group through the elderly individuals (Kruskal-Wallis: 13.7; p=0.003)., Conclusion: : In spite of being the patients most susceptible to complications due to surgical delay, the elderly individuals pre-sented the longest delays from admission to surgical treatment. Level of Evidence III, Retrospective Study.

Interleukin 6 (IL-6) is a pro-inflammatory cytokine upregulated in neurodegenerative contexts. The polymorphism IL-6 -174 G > C influences release levels of this cytokine. We aimed to evaluate the influence of IL-6 -174 G > C on global cognitive score of a group with cognitive impairment no dementia in one year of follow-up.Methods The subjects were categorized in two groups: short-term decline in global cognitive score and those with short-term stability or improvement. IL-6 174 G > C information were compared among these groups.Results We observed that individuals with cognitive impairment no dementia with GGlowergenotype were more frequent among global cognitive score non-decliners while carriers of at least one Chigherallele were more frequent in the group with global cognitive score decliners (p = 0.012; RR = 3.095 IC95%= 1.087-8.812).Conclusion These results suggest that the higher expression of IL-6 gene may be an independent risk factor for cognitive decline among individuals with cognitive impairment no dementia.

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity-as it has been defined and explored by cognitive neuroscience-in artistic creation and may provide leads for future lesion studies.

A higher level of educational attainment constitutes a protective factor against cognitive decline in the elderly. Nevertheless, the elements underpinning this association are yet not fully understood., Objective: The primary aim of this study was to compare cognitively impaired illiterate elderly subjects with cognitively preserved counterparts, according to demographics, comorbidities, lifetime habits and APOE genotype., Methods: This is a cross-sectional analysis of the illiterate subset of participants (n=174) from the Pietà study, a community-based survey of successful brain aging conducted in Caeté (MG), Brazil. Subjects were categorized into three diagnostic groups: cognitively normal (CN), cognitive impairment no-dementia (CIND) and dementia. The groups were then compared according to selected variables., Results: Subjects with dementia were older and had an increased prevalence of reported stroke or transient ischemic attack. The three groups did not differ in relation to demographics, prevalence of comorbidities, socioeconomic level, previous occupation profile and APOE-ε4 allele frequency. Qualitatively evaluated lifetime habits, such as alcohol consumption, smoking and physical activity engagement were also similar across groups., Conclusion: No associations were found between cognitive impairment/dementia and the variables evaluated in this community-based sample of illiterate elderly., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: Staging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD)., Objective: To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese., Methods: The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR)., Results: The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS., Conclusion: The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression., Competing Interests: Disclosure: The authors report no conflicts of interest.

Apathy is intimately associated with dementia. Unfortunately, its pathophysiology remains poorly understood. The motivational impairment that characterizes this disorder might share the same inflammatory mechanisms, as suggested by the sickness behavior theory., Objective: The primary aim of this study was to investigate the association between apathy symptoms and serum levels of tumor necrosis factor alpha (TNF-α) and its soluble receptors. Brain-derived neurotrophic factor (BDNF) levels were also analyzed since these have been associated with depression, a condition which shares abulic features with apathy., Methods: The sample consisted of 27 subjects with mild Alzheimer's disease or amnestic mild cognitive impairment, who were submitted to specific apathy evaluation using the Apathy Scale (AS) and provided blood samples for biomarker analysis. Participants were categorized into two groups according to median AS scores (17 points)., Results: Subjects with higher apathy symptoms (n=13) displayed higher levels of TNF-α soluble receptors (type 1: p=0.03; type 2: p=0.04). No other difference was found between groups., Conclusion: These findings point to the involvement of inflammatory mediators in the genesis of apathy symptoms, as suggested by the sickness behavior theory., Competing Interests: Disclosure: The authors report no conflicts of interest.

There are few studies describing the functional changes in behavioral variant frontotemporal dementia (bvFTD) and it is not clear which aspects of functionality are affected by the disease., Objective: The aim of the present investigation was to characterize the functional profile of patients previously diagnosed with bvFTD., Methods: The sample consisted of 31 patients diagnosed with bvFTD, who were compared to patients with Alzheimer's disease (AD) (n=31) and to healthy control subjects (NC) (n=34), matched for schooling and age. bvFTD and AD patients were matched by severity of dementia. The protocol included the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Direct Assessment of Functional Status (DAFS-BR), Functional Activities Questionnaire (PFAQ), Disability Assessment for Dementia (DAD) and the Clinical Dementia Rating scale (CDR)., Results: The group with bvFTD showed worse performance on Initiation and Planning/Organization in the DAD and on ability to feed oneself in the DAFS-BR, as well as higher scores on the PFAQ, suggesting greater dependence in the bvFTD group., Conclusion: The results suggest that individuals with bvFTD display greater functional impairment compared to AD patients with a similar degree of dementia severity and to healthy controls. Direct assessment of functionality proved unable to clearly differentiate between the dementia subtypes.

Introduction: Despite many advances in the characterization of the behavioral variant of frontotemporal dementia (bvFTD), the diagnosis of this syndrome poses a significant challenge, while delays or diagnostic mistakes may impact the proper clinical management of these patients., Objective: To describe the clinical profile at first evaluation of a sample of patients with bvFTD from a specialized outpatient neurological unit, with emphasis on the analysis of the delay between the onset of symptoms and diagnosis., Methods: We selected 31 patients that fulfilled international consensus criteria for possible or probable bvFTD. Patients' medical admission sheets were thoroughly reviewed., Results: Patients' mean age was 67.9±8.2 years; 16 (51.6%) were men. Mean number of years of formal education was 7.7±4.0 years. Mean age at onset was 62.2±7.7 years, indicating a mean of 5.8 years of diagnostic delay. Thirteen patients (41.9%) presented with initial behavioral complaints only, eleven patients (35.5%) had mixed behavioral and memory complaints, five patients (16.1%) presented with memory complaints only, and two patient (6.4%) had behavioral and speech problems. Nine patients (29%) were admitted with alternative diagnoses. Mean and standard deviation scores for the mini-mental state examination, animal category fluency and memory test for drawings (five-minute delayed recall) were 19.3±6.3, 8.3±4.1and 3.7±2.7, respectively., Conclusion: Most patients from this sample were evaluated almost six years after the onset of symptoms and performed poorly on both cognitive screening tests and functional evaluation measures., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objective: To show data on the performance of healthy subjects in the Frontal Assessment Battery (FAB), correlating with gender, age, education, and scores in the Mini-Mental State Examination (MMSE)., Methods: Two hundred and seventy-five healthy individuals with mean age of 66.4 ± 10.6 years-old were evaluated. Mean total FAB scores were established according to the educational level., Results: Mean total FAB scores according to the educational level were 10.9 ± 2.3, for one to three years; 12.8 ± 2.7, for four to seven years; 13.8 ± 2.2, for eight to 11 years; and 15.3 ± 2.3, for 12 or more years. Total FAB scores correlated significantly with education (r=0.47; p<0.0001) and MMSE scores (r=0.39; p<0.0001). No correlation emerged between FAB scores, age, and gender., Conclusion: In this group of healthy subjects, the Brazilian version of the FAB proved to be influenced by the education level, but not by age and gender.

Objectives: To present the methods and baseline characteristics of the Pietà study, a population-based survey investigating successful brain aging in the oldest-old., Method: The study was conducted in Caeté (MG), Brazil. In 2007, 1,251 individuals aged 75+ years were living in the city and were invited to participate. Participants responded to a general health questionnaire and were submitted to clinical, neurological, cognitive, psychiatric and functional evaluations. A subgroup was submitted to neuropsychological testing, blood tests and magnetic resonance of the skull. Individuals were classified as having cognitive impairment-no dementia, dementia, parkinsonism, psychiatric disorders or successful brain aging., Results: We evaluated 639 individuals (51.1% of the target population; 64% women), aged 81.4±5.2 years and with 2.7±2.6 years of schooling. Almost 30% of the elderly were illiterates and 82.1% belonged to middle/middle-low socioeconomic levels. Almost 50% were widows, but only 14.3% were living alone., Conclusion: The Pietà cohort is representative of the oldest-old Brazilian population. We believe the results of the study may contribute to increase our knowledge about healthy and pathological brain aging in the oldest-old.

No Brazilian version of a specific scale for evaluating apathy in dementia is available., Objectives: To introduce a translated version of the Apathy Scale (AS) for use with caregivers., Methods: The instrument was formally translated and then administered to the caregivers of a small sample of dementia patients, in order to assess scale comprehensibility and make final adjustments. The scale was subsequently administered to the caregivers of a second, independent sample of Alzheimer's disease (AD) patients. The content validity of the scale was tested by correlating the AS scores with the Neuropsychiatric Inventory (NPI) - apathy sub-score and Disability Assessment in Dementia (DAD) total scores., Results: The first sample consisted of eleven subjects with dementia, most of whom had AD. The second sample comprised twenty patients with probable or possible AD (10 with mild dementia), a mean age of 84.1±5.8 years, and 2.2±1.6 years of schooling. The AS scores correlated with both NPI-apathy sub-score (r=0.756, p=0.001) and DAD total scores (r=-0.793, p=0.0005)., Conclusions: The final version had good comprehensibility and correlated strongly with standardized apathy and functional activities of daily living measures., Competing Interests: Disclosure: The authors report no conflicts of interest.

Taking care of elderly demented individuals, especially when they present behavioral changes, can be very exhaustive for both family and caregivers. Generally, this leads to changes in the family lifestyle, and the caregiver must deal with a range of problems. Information on this topic in Latin America, including Brazil, remains scarce., Objective: To investigate the relationship between the presence of neuropsychiatric symptoms and the level of caregiver burden in a group of Brazilian elderly with dementia., Methods: The Brazilian versions of the Zarit Caregiver Burden Interview (ZBI) and of the Neuropsychiatric Inventory (NPI) were administered to a total of 83 family-caregivers of patients with dementia followed at a university-affiliated outpatient clinic. Pearson's correlations were calculated to measure the level of association between the scores on both instruments., Results: Among the caregivers, 83.1% were women, and had a mean age of 55.6±12.8 years. The ZBI scores ranged from 3 to 79 (mean=31.4). Patients' NPI scores ranged from 0 to 102 (mean=26.9), consistent with a significant degree of behavioral manifestations in most patients. A significant positive correlation was found between ZBI and NPI scores (r=0.402; p=0.000)., Conclusion: The presence and severity of behavioral manifestations assessed by the NPI were associated with a high level of caregiver burden in this sample of Brazilian elderly with dementia., Competing Interests: Disclosure: The authors report no conflicts of interest.

Apathy is considered the most frequent neuropsychiatric disturbance in dementia and its outcome is generally deleterious. Apathy can be related to a dysfunction of the anatomical-system that supports the generation of voluntary actions, namely the prefrontal cortex and/or the prefrontal-subcortical circuits. In Alzheimer's disease, pathological and neuroimaging data indicate that apathy is likely due to a dysfunction of the medial prefrontal cortex. Accordingly, in this review article, we propose a pathophysiological model to explain apathetic behavior in Alzheimer's disease, combining data from neuroimaging, neuropathology and experimental research on the role of orbito-frontal cortex, anterior cingulate cortex, basal ganglia and dopamine in decision-making neurobiology.

Objective: To investigate the prevalence of infection, disease and eventual institutional outbreak of tuberculosis in a psychiatric hospital using the PPD test, as well as testing for mycobacteria in material collected from the respiratory tree and using molecular tracking technique based on insertion sequence 6110 (IS6110)., Methods: Between February and August of 2002, PPD tests were given to 74 inpatients and 31 staff members at a psychiatric hospital in the city of Rio Verde, located in the state of Goiás, Brazil. In addition, respiratory tree material collected from the inpatients was submitted to testing for Mycobacterium tuberculosis., Results: Among the patients analyzed, mycobacteria were isolated from five (6.8%): four identified as M. tuberculosis and one as M. chelonae. The M. tuberculosis isolates were sensitive to isoniazid and rifampicin, and, when submitted to the restriction fragment length polymorphism/IS6110 technique, presented unique genetic profiles, totally distinct from one another, suggesting that all of the tuberculosis cases were due to endogenous reactivation. It was not possible to characterize this group of cases as an institutional outbreak. Performing the two-step tuberculin test in the patients, the infection rates were 23% and 31%, compared with 42% among staff members, who were submitted to the one-step test., Conclusion: The results indicate a high incidence of tuberculosis infection among inpatients and hospital staff, as well as a high occurrence of the disease among inpatients.

The objective of this research is to identify which nursing activities contained in the fluid management intervention proposed by the Nursing Intervention Classification (NIC) are realized and considered important by nurses, to attend patients who received fluid volume excess as a nursing diagnosis, as proposed by the North American Nursing Diagnoses Association (NANDA). Data were collected in three hospitals. The sample included 77 nurses, who chose the best alternative on a Likert scale, to indicate the realization of which of those actives they considered important and which activities are realized in their daily care practice. It was concluded that most of the nursing activities were always considered important and were always performed by the nurses. These activities were classified as independent and dependent.

The present study aimed to reflect on the importance of body language through the identification of what a graduate nursing group knew about this topic. We analyzed the contents of reports from which five categories emerged: concept, function, importance, meaning and forms of body language manifestation. The group valued body language as a complex way of interpersonal interaction that sometimes occurs out of our control and of which we have little conscience. It has the function of expressing feelings, emotions and transmitting messages whose meanings are influenced by context. Body language knowledge increases our professional perception and it is one more instrument to improve nursing assistance quality.

This study aimed at verifying the defining characteristics of the nursing diagnosis "Fluid Volume Excess" proposed by NANDA. Data collection was carried out within a specialized Cardiology health care setting where the 29 patients were selected by two expert nurses. The conclusion showed consonance of opinions between the two professionals in regard to the identification of nine patients with diagnosis and 20 without this type of diagnosis. The identified defining characteristics appeared in different percentages considering the studied patients.