Evaluation of the New Multi-HTLV Serological Assay: Improvement for HTLV-2 Detection.

Despite the accuracy of confirmatory tests for the diagnosis of human T cell lymphotropic virus (HTLV), inconclusive or false-negative results still occur when diagnosing human T cell lymphotropic virus type 2 (HTLV-2)-positive patients. The goal of this study was to evaluate the sensitivity and accuracy of a confirmatory immunoassay, the Multi-HTLV assay. A total of 246 plasma samples were tested by real-time polymerase chain reaction (qPCR) and used to calculate the sensitivity and typing accuracy of the Multi-HTLV assay. Of the 246 plasma samples, 127 were positive for human T cell lymphotropic virus type 1 (HTLV-1), 112 were positive for HTLV-2, and 7 were positive for both HTLV-1 and HTLV-2. Thereafter, the nonparametric Mann-Whitney U test was used to calculate the concordance between the qPCR test and Multi-HTLV assay in 12 samples with discrepant and inconclusive qPCR results. The Multi-HTLV assay showed high performance in identifying HTLV-1 and HTLV-2 with sensitivities of 97% [95% confidence interval (CI): 0.92-0.98] and 94% (0.87-0.96), respectively. However, due to typing performance (98% for HTLV-1 and 94% for HTLV-2), it had 95% agreement with positive HTLV-1 qPCR results (95% CI: 90.07-97.81) and 86% (78.04-91.01) of HTLV-2 qPCR results were positive. Moreover, this test was able to recognize 80% of indeterminate samples and all HTLV-2 positive samples that showed false-negative qPCR results. Our findings, derived from a substantial number of HTLV-positive samples, underscore the inherent reliability and feasibility of the Multi-HTLV assay, regardless of the molecular testing facilities. Furthermore, the distinctive multiparametric nature of this assay, combined with its straightforward procedural execution, introduces novel perspectives for analyzing specific serological profiles in each patient, as well as the potential for immunological monitoring of disease progression.

Current clinical and research practices on frontotemporal dementia in Brazil: a national survey.

BACKGROUND: Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care. OBJECTIVE: The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil. METHODS: We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology (n = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 (n = 187). The invitation was also diffused through social media. RESULTS: 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) (n = 211), bipolar disorder (n = 117) and dementia with Lewy bodies (n = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively. CONCLUSIONS: The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil.

ANTECEDENTES: A demência frontotemporal (DFT) é causa frequente de demência pré-senil e representa um desafio em termos de diagnóstico e de manejo clínico. É essencial avaliar as dificuldades existentes na propedêutica e nos cuidados médicos. OBJETIVO: Investigar as práticas médicas e as dificuldades para diagnóstico e manejo da DFT no Brasil. MéTODOS: Elaborou-se um questionário online, composto de 29 questões, divididas em quatro partes, com perguntas sobre infraestrutura existente, práticas clínicas relacionadas à DFT e sugestões para desenvolver a pesquisa nacional na área. O convite para participação foi enviado por e-mail a todos neurologistas afiliados à Academia Brasileira de Neurologia (n = 3658), e aos médicos que participaram da XII Reunião de Pesquisadores de Doença de Alzheimer, em 2019 (n = 187). O convite também foi divulgado através de mídias sociais. RESULTADOS: 256 médicos brasileiros responderam o questionário. Os três principais diagnósticos diferenciais de DFT foram doença de Alzheimer (n = 211), transtorno bipolar (n = 117) e demência com corpos de Lewy (n = 92). A maior parte dos respondedores (125/256) apontou a dificuldade em realizar testagem genética como o maior limite no diagnóstico de DFT. 93% e 63% dos respondedores indicaram que a avaliação de cognição social e o uso de biomarcadores liquóricos de doença de Alzheimer são úteis no diagnóstico de DFT, respectivamente. CONCLUSõES: Estes resultados devem ser considerados na educação e treinamento médicos, e no desenvolvimento da pesquisa brasileira em DFT.

Current clinical and research practices on frontotemporal dementia in Brazil: a national survey / Práticas clínicas e cenário de pesquisa em demência frontotemporal no Brasil: uma enquete nacional

Abstract Background Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care. Objective The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil. Methods We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology (n = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 (n = 187). The invitation was also diffused through social media. Results 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) (n = 211), bipolar disorder (n = 117) and dementia with Lewy bodies (n = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively. Conclusions The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil.

Resumo Antecedentes A demência frontotemporal (DFT) é causa frequente de demência pré-senil e representa um desafio em termos de diagnóstico e de manejo clínico. É essencial avaliar as dificuldades existentes na propedêutica e nos cuidados médicos. Objetivo Investigar as práticas médicas e as dificuldades para diagnóstico e manejo da DFT no Brasil. Métodos Elaborou-se um questionário online, composto de 29 questões, divididas em quatro partes, com perguntas sobre infraestrutura existente, práticas clínicas relacionadas à DFT e sugestões para desenvolver a pesquisa nacional na área. O convite para participação foi enviado por e-mail a todos neurologistas afiliados à Academia Brasileira de Neurologia (n = 3658), e aos médicos que participaram da XII Reunião de Pesquisadores de Doença de Alzheimer, em 2019 (n = 187). O convite também foi divulgado através de mídias sociais. Resultados 256 médicos brasileiros responderam o questionário. Os três principais diagnósticos diferenciais de DFT foram doença de Alzheimer (n = 211), transtorno bipolar (n = 117) e demência com corpos de Lewy (n = 92). A maior parte dos respondedores (125/256) apontou a dificuldade em realizar testagem genética como o maior limite no diagnóstico de DFT. 93% e 63% dos respondedores indicaram que a avaliação de cognição social e o uso de biomarcadores liquóricos de doença de Alzheimer são úteis no diagnóstico de DFT, respectivamente. Conclusões Estes resultados devem ser considerados na educação e treinamento médicos, e no desenvolvimento da pesquisa brasileira em DFT.

Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

Neuropsychological profile of patients with infectious disease: characterization and comparison of patients with HIV, HTLV, and HCV.

Understanding the effect of the HIV, HTLV-1, and HCV viruses on cognitive aspects can help in the better characterization of dementia, as well as the best conducts to be suitable for rehabilitation. Thus, the present study aimed to characterize and compare the neuropsychological profile of 3 groups of patients with infectious diseases: HIV, HTLV, and HCV. The results of neuropsychological assessments and depression assessment of 325 people treated at a referral hospital for infectious diseases were analyzed, being 120 HIV carriers (74 (61.7%) men) with an average age of 47.5 years (SD = 10.3), 65 patients with HTLV-1 (16 (24.6%) men) with a mean age of 49.9 years (SD = 12.9), and 87 HCV patients (47 (54%) men) with a mean age of 55.5 years (SD = 11.2). In addition, 54 people (26 (48.1%) men) with negative serology who made up the control group were evaluated. The results of the statistical evaluation of the sociodemographic factors of the four groups (HIV, HTLV-1, HCV, and control) showed that in addition to age, schooling was a significant factor among them and may have a strong influence on the performance of cognitive tests. The HTLV-1 group had the lowest neurocognitive performance and also the highest rate of depressive symptoms.

Treatment of dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

There is currently no cure for neurodegenerative or vascular dementias, but some pharmacological and non-pharmacological interventions may contribute to alleviate symptoms, slow disease progression and improve quality of life. Current treatment approaches are based on etiology, symptom profile and stage of dementia. This manuscript presents recommendations on pharmacological and non-pharmacological treatments of dementia due to Alzheimer's disease, vascular cognitive impairment, frontotemporal dementia, Parkinson's disease dementia, and dementia with Lewy bodies.

Atualmente não há tratamento curativo para as demências neurodegenerativas ou para a demência vascular, mas algumas intervenções farmacológicas e não farmacológicas podem contribuir para aliviar os sintomas, retardar a progressão da doença e melhorar a qualidade de vida. As abordagens terapêuticas atuais são baseadas na etiologia, no perfil dos sintomas e no estágio da demência. Neste artigo apresentamos recomendações sobre os tratamentos farmacológicos e não farmacológicos da demência devida à doença de Alzheimer, comprometimento cognitivo vascular, demência frontotemporal, demência da doença de Parkinson e demência com corpos de Lewy.

Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers.

A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

Diagnosis of frontotemporal dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

"Frontotemporal dementia" (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging.

A "demência frontotemporal" (DFT) é uma síndrome clínica, cujo denominador comum é o acometimento focal dos lobos frontais e/ou temporais. A DFT tem três fenótipos clínicos distintos: a variante comportamental e dois subtipos linguísticos, a saber, a afasia progressiva primária não-fluente/agramática (APP-NF/A) e a afasia progressiva primária semântica (APP-S). A DFT é a segunda causa mais comum de demência em indivíduos com idade inferior a 65 anos, após a doença de Alzheimer. O presente artigo apresenta recomendações para diagnóstico da DFT no cenário brasileiro, considerando os três níveis de complexidade do sistema de saúde: atenção primária à saúde e níveis secundários. São propostos protocolos de investigação diagnóstica abrangendo testagem cognitiva, avaliação comportamental, avaliação fonoaudiológica, exames laboratoriais e de neuroimagem.

Diagnosis and management of Parkinson's disease dementia and dementia with Lewy bodies: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts.

A demência da doença de Parkinson (DDP) e a demência com corpos de Lewy (DCL) representam a segunda causa mais comum de demência neurodegenerativa em pessoas com mais de 65 anos, ocasionando progressivo declínio cognitivo e comprometimento da qualidade de vida. O presente estudo tem como objetivo prover um consenso de especialistas sobre a DDP e DCL, baseado em revisão sistemática da literatura brasileira e revisão não-sistemática de literatura internacional. Ademais, tal estudo visa promover informação e conceder recomendações sobre abordagem diagnóstica, com foco nos níveis de atenção primária e secundária em saúde. Com base nos dados disponíveis, recomendamos que os profissionais realizem pelo menos um breve instrumento cognitivo global, como o Mini-Exame do Estado Mental, contudo de preferência optem pela Avaliação Cognitiva de Montreal e o Exame Cognitivo de Addenbrooke-Revisado. Observa-se uma carência de instrumentos validados para a avaliação precisa das habilidades funcionais em pacientes brasileiros com DDP e DCL. Além disso, mais estudos focando em biomarcadores com coortes brasileiras também são necessários.

Subjective cognitive decline, mild cognitive impairment, and dementia - syndromic approach: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This consensus, performed by the Brazilian Academy of Neurology (BAN) will approach practically how to evaluate patients with cognitive complaints and how to clinically and etiologically diagnose the three clinical syndromes associated with the different stages of cognitive decline: subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. This BAN consensus discusses SCD diagnosis for the first time, updates MCI and dementia diagnoses, recommends the adequate cognitive tests and the relevant etiological work-up and care of patients with cognitive decline at different levels of care within the Brazilian Unified Health System. We also review the main assessment instruments used in Brazil and Latin America.

Este consenso realizado pela Academia Brasileira de Neurologia (ABN) abordará de maneira prática como avaliar pacientes com queixas cognitivas e como realizar o diagnóstico clínico e etiológico das três síndromes clínicas associadas aos estágios de declínio cognitivo: declínio cognitivo subjetivo (DCS), comprometimento cognitivo leve (CCL) e demência. O diagnóstico de DCS é discutido pela primeira vez em consenso da ABN e as atualizações para o diagnóstico de CCL e demência são abordadas, bem como a recomendação para o uso de testes cognitivos apropriados, investigação etiológica pertinente e cuidados aos pacientes com declínio cognitivo nos diferentes níveis de atenção do Sistema Único de Saúde. Foi realizada pesquisa dos principais instrumentos de avaliação utilizados em nosso meio e na América Latina.

Diagnosis of vascular cognitive impairment: recommendations of the scientific department of cognitive neurology and aging of the Brazilian Academy of Neurology.

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

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

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation.

BACKGROUND: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. PATIENTS AND METHODS: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. RESULTS: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. CONCLUSIONS: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.

Diagnóstico e manejo da demência da doença de Parkinson e demência com corpos de Lewy: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis and management of Parkinson's disease dementia and dementia with Lewy bodies: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO A demência da doença de Parkinson (DDP) e a demência com corpos de Lewy (DCL) representam a segunda causa mais comum de demência neurodegenerativa em pessoas com mais de 65 anos, ocasionando progressivo declínio cognitivo e comprometimento da qualidade de vida. O presente estudo tem como objetivo prover um consenso de especialistas sobre a DDP e DCL, baseado em revisão sistemática da literatura brasileira e revisão não-sistemática de literatura internacional. Ademais, tal estudo visa promover informação e conceder recomendações sobre abordagem diagnóstica, com foco nos níveis de atenção primária e secundária em saúde. Com base nos dados disponíveis, recomendamos que os profissionais realizem pelo menos um breve instrumento cognitivo global, como o Mini-Exame do Estado Mental, contudo de preferência optem pela Avaliação Cognitiva de Montreal e o Exame Cognitivo de Addenbrooke-Revisado. Observa-se uma carência de instrumentos validados para a avaliação precisa das habilidades funcionais em pacientes brasileiros com DDP e DCL. Além disso, mais estudos focando em biomarcadores com coortes brasileiras também são necessários.

ABSTRACT Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts.

Tratamento da demência: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Treatment of dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO Atualmente não há tratamento curativo para as demências neurodegenerativas ou para a demência vascular, mas algumas intervenções farmacológicas e não farmacológicas podem contribuir para aliviar os sintomas, retardar a progressão da doença e melhorar a qualidade de vida. As abordagens terapêuticas atuais são baseadas na etiologia, no perfil dos sintomas e no estágio da demência. Neste artigo apresentamos recomendações sobre os tratamentos farmacológicos e não farmacológicos da demência devida à doença de Alzheimer, comprometimento cognitivo vascular, demência frontotemporal, demência da doença de Parkinson e demência com corpos de Lewy.

ABSTRACT There is currently no cure for neurodegenerative or vascular dementias, but some pharmacological and non-pharmacological interventions may contribute to alleviate symptoms, slow disease progression and improve quality of life. Current treatment approaches are based on etiology, symptom profile and stage of dementia. This manuscript presents recommendations on pharmacological and non-pharmacological treatments of dementia due to Alzheimer's disease, vascular cognitive impairment, frontotemporal dementia, Parkinson's disease dementia, and dementia with Lewy bodies.

Manejo das demências em fase avançada: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

ABSTRACT Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers.

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

ABSTRACT This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Declínio cognitivo subjetivo, comprometimento cognitivo leve e demência - diagnóstico sindrômico: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Subjective cognitive decline, mild cognitive impairment, and dementia - syndromic approach: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO Este consenso realizado pela Academia Brasileira de Neurologia (ABN) abordará de maneira prática como avaliar pacientes com queixas cognitivas e como realizar o diagnóstico clínico e etiológico das três síndromes clínicas associadas aos estágios de declínio cognitivo: declínio cognitivo subjetivo (DCS), comprometimento cognitivo leve (CCL) e demência. O diagnóstico de DCS é discutido pela primeira vez em consenso da ABN e as atualizações para o diagnóstico de CCL e demência são abordadas, bem como a recomendação para o uso de testes cognitivos apropriados, investigação etiológica pertinente e cuidados aos pacientes com declínio cognitivo nos diferentes níveis de atenção do Sistema Único de Saúde. Foi realizada pesquisa dos principais instrumentos de avaliação utilizados em nosso meio e na América Latina.

ABSTRACT This consensus, performed by the Brazilian Academy of Neurology (BAN) will approach practically how to evaluate patients with cognitive complaints and how to clinically and etiologically diagnose the three clinical syndromes associated with the different stages of cognitive decline: subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. This BAN consensus discusses SCD diagnosis for the first time, updates MCI and dementia diagnoses, recommends the adequate cognitive tests and the relevant etiological work-up and care of patients with cognitive decline at different levels of care within the Brazilian Unified Health System. We also review the main assessment instruments used in Brazil and Latin America.

Diagnóstico da demência frontotemporal: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis of frontotemporal dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO A "demência frontotemporal" (DFT) é uma síndrome clínica, cujo denominador comum é o acometimento focal dos lobos frontais e/ou temporais. A DFT tem três fenótipos clínicos distintos: a variante comportamental e dois subtipos linguísticos, a saber, a afasia progressiva primária não-fluente/agramática (APP-NF/A) e a afasia progressiva primária semântica (APP-S). A DFT é a segunda causa mais comum de demência em indivíduos com idade inferior a 65 anos, após a doença de Alzheimer. O presente artigo apresenta recomendações para diagnóstico da DFT no cenário brasileiro, considerando os três níveis de complexidade do sistema de saúde: atenção primária à saúde e níveis secundários. São propostos protocolos de investigação diagnóstica abrangendo testagem cognitiva, avaliação comportamental, avaliação fonoaudiológica, exames laboratoriais e de neuroimagem.

ABSTRACT "Frontotemporal dementia" (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging.

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

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

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