Diagnóstico de la variante conductual de demencia frontotemporal basado en estadios clínicos adaptado para países con baja educación: el caso de Perú

Demencia frontotemporal (DFT) es una condición neurodegenerativa escasamente reconocida en personas menores a 65 años de edad. El diagnóstico de DFT variante conductual (DFTvc) se basa en una entrevista clínica comprehensiva, complementada por una evaluación multidimensional (neurológica, cognitiva, neuropsiquiátrica, de biomarcadores e imágenes cerebrales) adaptada y validada a la población a estudiar; sin embargo, a pesar del incremento de su prevalencia en Latinoamérica y el Caribe, existe necesidad de herramientas estandarizadas y un consenso para el diagnóstico de DFTvc. El artículo intenta realizar una aproximación del enfoque de diagnóstico de DFTvc en escenario de paises con bajos y medianos ingresos, como el Perú.

Frontotemporal dementia (FTD) is a widely recognized neurodegenerative condition in people under 65 years old. The diagnosis of behavioral variant FTD (bvFTD) is based on a comprehensive clinical assessment, complemented by a multidimensional assessment (neurological, cognitive, neuropsychiatric, biomarker and brain imaging) adapted and validated to the population to be studied; however, despite its increasing prevalence in Latin America and the Caribbean, there is a need for standardized tools and consensus for the bvFTD diagnosis. The manuscript attempts to approximate the approach for the diagnosis of bvFTD in the setting of low and middle-income countries, including Peru.

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.

A variant in GRN of Spanish origin presenting with heterogeneous phenotypes.

INTRODUCTION: The variant c.1414-1G>T in the GRN gene has previously been reported as probably pathogenic in subjects of Hispanic origin in the American continent. METHODS: We report 5 families of Spanish origin carrying this variant, including the clinical, neuroimaging, and laboratory findings. RESULTS: Phenotypes were strikingly different, including cases presenting with behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, rapidly progressive motor neuron disease (pathologically documented), and tremor-dominant parkinsonism. Retinal degeneration has been found in homozygous carriers only. Ex vivo splicing assays confirmed that the mutation c.1414-1G>T affects the splicing of the exon, causing a loss of 20 amino acids in exon 11. CONCLUSIONS: We conclude that variant c.1414-1G>T of the GRN gene is pathogenic, can lead to a variety of clinical presentations and to gene dosage effect, and probably has a Spanish founder effect.

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.

How to differentiate behavioral variant frontotemporal dementia from primary psychiatric disorders: practical aspects for the clinician / Como diferenciar variante comportamental da demência frontotemporal de transtornos psiquiátricos: aspectos práticos para o clínico

ABSTRACT Background: Due to the early and prominent behavioral changes which characterize behavioral variant frontotemporal dementia (bvFTD), patients are more likely to seek psychiatric help and are often initially diagnosed with a primary psychiatric disorder (PPD). Differentiating these conditions is critical because of the dramatically different outcomes, differences in patient management, family counseling and caregiver education. Objective: To propose a practical guide to distinguish between bvFTD and PDD. Methods: We conducted a non-systematic review of the published manuscripts in the field, including some previous investigations from our own group and work on which we have collaborated, and summarized the main findings and proposals that may be useful for neurological practice. Results: The reviewed literature suggests that a comprehensive clinical history, brief cognitive and neuropsychological evaluations, detailed neurological examination with special attention to motor alterations related to bvFTD, structural and functional neuroimaging evaluation, genetic investigation in selected cases, and assistance from a multidisciplinary team, including a neurologist and a psychiatrist with expertise in bvFTD, are very helpful in differentiating these conditions. Conclusions: Although the clinician may commonly face great difficulty in differentiating between bvFTD and PPD, the use of appropriate tools in a systematic way and the availability of a well-trained multidisciplinary group can significantly increase diagnostic accuracy.

RESUMO Antecedentes: Devido às alterações comportamentais precoces e proeminentes que caracterizam a variante comportamental da demência frontotemporal (DFTvc), os pacientes são mais propensos a procurar atendimento psiquiátrico e muitas vezes são diagnosticados inicialmente com um transtorno psiquiátrico primário (TPP). Diferenciar essas condições é fundamental, devido aos desfechos significativamente diferentes, diferenças no manejo dos pacientes, no aconselhamento familiar e na educação dos cuidadores. Objetivo: Propor um guia prático para o diagnóstico diferencial entre DFTvc e TPP. Métodos: Revisão não sistemática dos manuscritos publicados na área, incluindo algumas investigações anteriores de nosso próprio grupo e trabalhos com os quais colaboramos. Os principais achados e propostas foram sintetizados para auxiliarem a prática neurológica. Resultados: A literatura revisada sugere que a história clínica abrangente, avaliação cognitiva breve e avaliação neuropsicológica, exame neurológico detalhado com especial atenção às alterações motoras relacionadas à DFTvc, exames de neuroimagem estrutural e funcional, investigação genética em casos selecionados e o atendimento por equipe multidisciplinar, incluindo um neurologista e um psiquiatra com experiência em DFTvc, são bastante úteis na diferenciação dessas condições. Conclusões: Embora o clínico possa enfrentar grande dificuldade para diferenciar DFTvc e TPP, o uso de ferramentas apropriadas de forma sistemática e a disponibilidade de uma equipe multidisciplinar bem treinada podem aumentar significativamente a acurácia diagnóstica.

Genetic investigation of dementias in clinical practice / Investigação genética das demências na prática clínica

Abstract Background: The field of neurodegenerative dementia genetics has advanced significantly over the past two decades, but there are still more to be discovered (such as the gene mutation in some familial forms of dementia). Objective: to provide a brief review of the most recent discoveries regarding monogenic dementia, and covering the most frequent genetic diseases that can cause dementia (neurodegenerative or not). Methods: a review of the literature will be carried out. Results: neurodegenerative dementias, vascular dementias and leukoencephalopathies caused by single pathogenic variants are presented. Conclusion: The spectrum of clinical presentations for most of the genes discussed is wide, and hence genetic testing in clinic should try to cover as many genes as possible.

RESUMO Antecedentes: O campo da genética das demências neurodegenerativas avançou significativamente nas últimas duas décadas, mas ainda há mais a ser descoberto (como a mutação genética em algumas formas familiares de demência). Objetivo: fornecer uma breve revisão das descobertas mais recentes sobre demência monogênica, e abrangendo as doenças genéticas mais frequentes que podem causar demência (neurodegenerativa ou não). Métodos: será realizada uma revisão da literatura. Resultados: são apresentadas demências neurodegenerativas, demências vasculares e leucoencefalopatias causadas por variantes patogênicas únicas. Conclusão: O espectro de apresentações clínicas para a maioria dos genes discutidos é amplo e, portanto, os testes genéticos na clínica devem tentar cobrir o maior número possível de genes.

Estudio comparativo de la capacidad denominativa y la memoria episódica de los pacientes con demencia degenerativa / Comparative Study of the Word Capacity and Episodic Memory of Patients with Degenerative Dementia

RESUMEN Introducción: Aunque la ausencia de deterioro de la memoria se consideró entre los criterios diagnósticos para diferenciar la enfermedad de Alzheimer (EA) de la demencia frontotemporal variante conductual (DFTvC), la evidencia actual, en aumento, sería la un importante porcentaje de casos de DFTvC con déficits de la memoria episódica. El presente estudio se diseñó con el fin de comparar el perfil de desempeño de la capacidad denominativa y de la memoria episódica de los pacientes con EA y DFTvC. Métodos: Estudio transversal y analítico con grupo de control (n = 32). Se incluyó a 42 sujetos con probable EA y 22 con probable DFTvC, todos mayores de 60 años. Se utilizaron instrumentos del Uniform Data Set validados en español: Multilingual Naming Test (MINT), historia de Craft-21 y Figura compleja de Benson, entre otros. Resultados: Se observó un mayor promedio de edad entre los pacientes con EA. La capacidad denominativa fue mucho menor en los pacientes con DFTvC que en aquellos con EA, medida según el MINT y el coeficiente de denominación sustantivos/verbos. Todos los pacientes con DFTvC, el 73,81% de aquellos con EAy solo el 31,25% de los controles no lograron reconocer la Figura compleja de Benson. Todas las diferencias fueron estadísticamente significativas (p< 0,001). Resultados: Este estudio confirma el perfil amnésico de los pacientes con EA y revela la disminución de la capacidad denominativa de los pacientes con DFTvC, un área del lenguaje que se afecta típica y tempranamente con las funciones ejecutivas, según recientes hallazgos. Conclusiones: Los pacientes con EA rinden peor en las tareas de memoria episódica verbal y visual, mientras que los pacientes con DFTvC rinden peor en tareas de denominación. Estos hallazgos abren la posibilidad de explorar los mecanismos de participación prefrontal en la memoria episódica, típicamente atribuida al hipocampo.

ABSTRACT Introduction: Although the absence of memory impairment was considered among the Alzheimer's disease diagnostic criteria to differentiate Alzheimer's disease (AD) from Behavioural Variant of Frontotemporal dementia Frontotemporal Dementia (bvFTD), current and growingevidence indicates that a significant Neuropsychological assessment percentage of cases of bvFTD present with episodic memory deficits. In order to compare Memory the performance profile of the naming capacity and episodic memory in patients with AD and bvFTD the present study was designed. Methods: Cross-sectional and analytical study with control group (32 people). The study included 42 people with probable AD and 22 with probable bvFTD, all over 60 years old. Uniform Data Set instruments validated in Spanish were used: Multilingual Naming Test (MINT), Craft-21 history and Benson's complex figure, among others. Results: A higher average age was observed among the patients with AD. The naming capacity was much lower in patients with bvFTD compared to patients with AD, measured according to the MINT and the nouns/verbs naming coefficient. All patients with bvFTD, 73.81% of those with AD and only 31.25% of the control group failed to recognise Benson's complex figure. All differences were statistically significant (p < 0.001). Results:This study confirms the amnesic profile of patients with AD and reveals the decrease in naming capacity in patients with bvFTD, an area of language that is typically affected early on with executive functions, according to recent findings. Conclusions: Patients with AD perform worse in verbal and visual episodic memory tasks, while patients with bvFTD perform worse in naming tasks. These findings open the possibility of exploring the mechanisms of prefrontal participation in episodic memory, typically attributed to the hippocampus.

Comparative study of the word capacity and episodic memory of patients with degenerative dementia.

INTRODUCTION: Although the absence of memory impairment was considered among the diagnostic criteria to differentiate Alzheimer's disease (AD) from Behavioural Variant of Frontotemporal Dementia (bvFTD), current and growing evidence indicates that a significant percentage of cases of bvFTD present with episodic memory deficits. In order to compare the performance profile of the naming capacity and episodic memory in patients with AD and bvFTD the present study was designed. METHODS: Cross-sectional and analytical study with control group (32 people). The study included 42 people with probable AD and 22 with probable bvFTD, all over 60 years old. Uniform Data Set instruments validated in Spanish were used: Multilingual Naming Test (MINT), Craft-21 history and Benson's complex figure, among others. RESULTS: A higher average age was observed among the patients with AD. The naming capacity was much lower in patients with bvFTD compared to patients with AD, measured according to the MINT and the nouns/verbs naming coefficient. All patients with bvFTD, 73.81% of those with AD and only 31.25% of the control group failed to recognise Benson's complex figure. All differences were statistically significant (p < 0.001). RESULTS: This study confirms the amnesic profile of patients with AD and reveals the decrease in naming capacity in patients with bvFTD, an area of ​​language that is typically affected early on with executive functions, according to recent findings. CONCLUSIONS: Patients with AD perform worse in verbal and visual episodic memory tasks, while patients with bvFTD perform worse in naming tasks. These findings open the possibility of exploring the mechanisms of prefrontal participation in episodic memory, typically attributed to the hippocampus.

Spanish version of the frontotemporal dementia knowledge scale: adaptation and validation / Versión en español de la escala de conocimiento sobre demencia frontotemporal: adaptación y validación

ABSTRACT Background: Frontotemporal dementia (FTD) is a neurodegenerative disease and is one of the most common causes of dementia in people under 65. There is often a significant diagnostic delay, as FTD can be confused with other psychiatric conditions. A lack of knowledge regarding FTD by health professionals is one possible cause for this diagnostic confusion. Objectives: The aim of this study was to adapt and validate the Frontotemporal Dementia Knowledge Scale (FTDKS) in Spanish. Methods: A translation was done, following cross-cultural adaptation guidelines, which consisted of forward translation, blind back translation, and an analysis by a committee of experts. For the present study, 134 professionals from different health areas responded the Spanish version of the FTDKS. The statistical analysis was performed using R version 4.0.0 "Arbor day" and the Psych, sjPlot packages. Results: The Spanish version of the FTDKS had good reliability and internal consistency (Cronbach alpha 0.74.). The sample's mean score was 19.78 (range = 4-32, SD 6.3) out of a maximum of 36 points. Conclusions: The results obtained show that the Spanish version has good psychometric properties. The FTDKS is applicable in our environment and can be a useful tool to evaluate the knowledge of health professionals regarding frontotemporal dementia.

RESUMEN Antecedentes: La demencia frontotemporal (DFT) es una enfermedad neurodegenerativa y es una de las causas más comunes de demencia en personas menores de 65 años. A menudo existe un retraso significativo en el diagnóstico, ya que la FTD puede confundirse con otras afecciones psiquiátricas. La falta de conocimientos sobre la DFT por parte de los profesionales de salud es una posible causa de esta confusión diagnóstica. Objetivos: El presente estudio describe nuestros esfuerzos para adaptar y validar la Escala de Conocimiento de la Demencia Frontotemporal (FTDKS) en español. Métodos: Se realizó una traducción, siguiendo las pautas de adaptación transcultural, que consistió en una traducción directa, una traducción inversa ciega y un análisis por parte de un comité de expertos. Para el presente estudio, 134 profesionales de diferentes áreas de la salud respondieron la versión en español del FTDKS. El análisis estadístico se realizó utilizando la versión 4.0.0 de R "Arbor day" y los paquetes Psych, sjPlot. Resultados: La versión en español del FTDKS tiene una buena fiabilidad y consistencia interna (alfa de Cronbach 0,74.). La puntuación media de la muestra fue de 19,78 (rango = 4-32, SD 6,3) sobre un máximo de 36 puntos. Conclusiones: Los resultados obtenidos muestran que la versión española tiene buenas propiedades psicométricas. El FTDKS es aplicable en nuestro medio y puede ser una herramienta útil para evaluar los conocimientos de los profesionales sanitarios sobre la demencia frontotemporal.

Estudio preliminar de variables temporales del habla continua en pacientes con síndromes neurodegenerativos del espectro degeneración lobar frontotemporal / Preliminary study of the temporal variables of continuous speech in patients with neurodegenerative syndromes of the frontotemporal lobar degeneration spectrum

Introducción: Las enfermedades neurodegenerativas, especialmente la degeneración lobar frontotemporal y la enfermedad de Alzheimer, conllevan a menudo una alteración de las funciones del lenguaje, por lo que el análisis del habla puede proporcionar medidas objetivas para clasificar los diferentes síndromes. Objetivo: Estudiar la naturaleza, correlatos cognitivos y utilidad clínica de 21 variables relacionadas con el tiempo de habla y de silencio. Sujetos y métodos: Derivación de variables acústicas con Praat en tres tareas de habla espontánea en 22 sujetos, distribuidos en seis grupos de diagnóstico (cinco con enfermedades neurodegenerativas + control). Se realiza un análisis descriptivo, con curvas ROC y de componentes principales, para estudiar cómo las variables acústicas se relacionan con los distintos síndromes neurodegenerativos y qué información pueden aportar. Resultados: Se identifican tres grupos de variables relacionadas, respectivamente, con: a) número total de pausas silenciosas y duración total de la tarea; b) variabilidad de los grupos fónicos, y c) variabilidad de los períodos de silencio. Dichas componentes se correlacionan diferencialmente con los distintos síndromes estudiados. Conclusiones: El análisis detallado del tiempo de habla y de silencio puede aportar información relevante para el diagnóstico de diferentes síndromes neurodegenerativos, no reflejado en las evaluaciones de neuropsicología tradicionales. Así, el número total de pausas silenciosas puede tener valor para discriminar los pacientes con déficits de acceso léxico, los parámetros del grupo fónico parecen reflejar los problemas motores del habla, mientras que la variabilidad de las pausas se asocia con el deterioro disejecutivo y global.(AU)

Introduction: Neurodegenerative diseases, especially frontotemporal lobar degeneration and Alzheimer’s disease, often lead to impaired language functions, and so speech analysis can provide objective measures with which to classify the different syndromes. Aim: To study the nature, cognitive correlates and clinical utility of 21 variables related to speech and silence times. Subjects and methods. Derivation of acoustic variables with Praat in three spontaneous speech tasks conducted in 22 subjects, distributed in six diagnostic groups (five with neurodegenerative diseases + control). A descriptive analysis is performed, with ROC and principal component curves, to study how acoustic variables are related to the different neurodegenerative syndromes and what information they can provide. Results: Three groups of variables are identified related, respectively, to: a) total number of silent pauses and total duration of the task; b) variability of the phonic groups; and c) variability of the periods of silence. These components correlate differentially with the different syndromes studied. Conclusions: Detailed analysis of speech and silence times can provide relevant information for the diagnosis of different neurodegenerative syndromes that are not reflected in traditional neuropsychological assessments. Thus, the total number of silent pauses may be a valuable aid in discriminating patients with lexical access deficits, phonic group parameters seem to reflect motor speech problems, and pause variability is associated with dysexecutive and global impairment.(AU)

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

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

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

Demencia frontotemporal desde una mirada neuropsicológica / Frontotemporal dementia from a neuropsychological point of view

Introducción: La riqueza de las manifestaciones neuropsicológicas de la demencia frontotemporal, ha permitido la identificación de diferentes variantes de la enfermedad, sin embargo, existen pacientes en los que se entrelazan las características clínicas de más de una variante, lo que ha llevado a cuestionar lo relativo de las clasificaciones vigentes. Objetivo: Caracterizar el funcionamiento cognitivo de un paciente donde concomitan alteraciones conductuales y del lenguaje, típicas de la demencia frontotemporal. Caso clínico: Mujer diestra, de 50 años de edad, con cambios conductuales marcados, a los cuales, de forma progresiva, se sumaron alteraciones del lenguaje, en un periodo de evolución de aproximadamente un año y seis meses. Por imágenes de tomografía axial computarizada, se confirma atrofia cortical a predominio frontal. Se emplearon para la evaluación la batería neuropsicológica breve NEUROPSI, la escala Hasegawa y la batería de evaluación frontal de Litvan; se constata predominio de alteraciones en el lenguaje impresivo y expresivo, las funciones ejecutivas y en la memoria verbal. Conclusiones: Las alteraciones detectadas, confirman la coexistencia de manifestaciones de la variante conductual (con tendencia a la desinhibición) y la variante semántica de la demencia frontotemporal(AU)

Introduction: The richness of the neuropsychological manifestations of frontotemporal dementia has allowed the identification of different variants of the disease. However, there are patients in whom the clinical characteristics of more than one variant are intertwined, which has led to question the current classifications. Objective: To characterize the cognitive functioning of a patient with concomitant behavioral and language disorders, typical of frontotemporal dementia. Case presentation: Right-handed female, 50 years old, affected by marked behavioral changes, to which language alterations were progressively added in a period of evolution of approximately one year and six months. Images of Computerized Axial Tomography that confirm cortical atrophy mainly frontal. The Neuropsychological Battery abbreviated NEUROPSI, the Hasegawa Scale and the Litvan Frontal Evaluation Battery were used for the evaluation, with a predominance of alterations in printed and expressive language, executive functions and verbal memory. Conclusions: The alterations detected confirm the coexistence of manifestations of the behavioral variant (with a tendency to disinhibition) and the semantic variant of frontotemporal dementia(AU)

Recognition of musical emotions in the behavioral variant of frontotemporal dementia.

INTRODUCTION: Multiple investigations have revealed that patients with behavioral variant of frontotemporal dementia (bvFTD) experience difficulty recognizing emotional signals in multiple processing modalities (e.g., faces, prosody). Few studies have evaluated the recognition of musical emotions in these patients. This research aims to evaluate the ability of subjects with bvFTD to recognize musical stimuli with positive and negative emotions, in comparison with healthy subjects. METHODS: bvFTD (n=12) and healthy control participants (n=24) underwent a test of musical emotion recognition: 56 fragments of piano music were randomly reproduced, 14 for each of the emotions (happiness, sadness, fear, and peacefulness). RESULTS: In the subjects with bvFTD, a mean of correct answers of 23.6 (42.26%) was observed in contrast to the control subjects, where the average number of correct answers was 36.3 (64.8%). Statistically significant differences were found for each of the evaluated musical emotions and in the total score on the performed test (P<.01). The within-group analysis showed greater difficulty for both groups in recognizing negative musical emotions (sadness, fear), with the subjects with bvFTD exhibiting worse performance. CONCLUSIONS: Our results indicate that the recognition of musical stimuli with positive (happiness, peacefulness) and negative (sadness, fear) emotions are compromised in patients with bvFTD. The processing of negative musical emotions is the most difficult for these individuals.

Curso clínico y perfil neuropsicológico de un caso de trastorno neurocognitivo frontotemporal mayor variante lingüística / Clinical course and neuropsychological profile of Frontotemporal Neurocognitive Disorder Linguistic Language Variant

Resumen El trastorno neurocognitivo frontotemporal es una enfermedad neurodegenerativa que incluye manifestaciones clínicas de subtipo comportamental y lingüística. La afasia progresiva primaria (APP) es un síndrome en el que aparecen alteraciones del lenguaje que comprende tres tipos de variantes: no fluente, semántica y logopénica. Este estudio describe la evolución clínica y las características neuropsicológicas de una mujer de 63 años que presenta un deterioro progresivo del lenguaje. Se evalúan las funciones de atención, memoria, lenguaje y funciones ejecutivas. La paciente obtuvo un bajo rendimiento en memoria, velocidad de procesamiento y funciones ejecutivas. Su lenguaje se caracteriza por presentar baja fluidez, agramatismo, parafasias verbales y dificultades en denominación. Se concluye que la paciente presenta características de la APP no fluente, que varía a través del tiempo y afecta su funcionamiento; características de un curso clínico de un trastorno neurocognitivo mayor posible debido a una degeneración del lóbulo frontotemporal.

Abstract Mild cognitive impairment, frontotemporal dementia (FTD) is a neurodegenerative disease characterized by clinical manifestations of behavior and linguistic subtypes. Primary Progressive Aphasia (APP) is a syndrome in which language alterations appear that include three types of variations: Non - fluent, Semantic and Logopenic. This study describes the clinical evolution and the neurophysiological characteristics of a 63 years old woman that started with a progressive language impairment. The functions which are evaluated are attention, memory, language and executive functions. The patient obtained a low performance in memory, processing speed and executive functions. The language is characterized by low fluency, agramatism, paraphasias and denomination difficulties. It is concluded, that the patient has characteristics of APP non-fluent which varies throughout the time and it affects her performance; characteristics of a clinical course of a greater neurocognitive disorder might be due to a lobe frontotemporal degeneration.

Recognition of musical emotions in the behavioral variant of frontotemporal dementia / Reconocimiento de emociones musicales en la variante conductual de la demencia frontotemporal

ABSTRACT Introduction: Multiple investigations have revealed that patients with behavioral variant of frontotemporal dementia (bvFTD) experience difficulty recognizing emotional signals in multiple processing modalities (e.g., faces, prosody). Few studies have evaluated the recognition of musical emotions in these patients. This research aims to evaluate the ability of subjects with bvFTD to recognize musical stimuli with positive and negative emotions, in comparison with healthy subjects. Methods: bvFTD (n = 12) and healthy control participants (n = 24) underwent a test of musical emotion recognition: 56 fragments of piano music were randomly reproduced, 14 for each of the emotions (happiness, sadness, fear, and peacefulness). Results: In the subjects with bvFTD, a mean of correct answers of 23.6 (42.26%) was observed in contrast to the control subjects, where the average number of correct answers was 36.3 (64.8%). Statistically significant differences were found for each of the evaluated musical emotions and in the total score on the performed test (P<.01). The within-group analysis showed greater difficulty for both groups in recognizing negative musical emotions (sadness, fear), with the subjects with bvFTD exhibiting worse performance. Conclusions: Our results indicate that the recognition of musical stimuli with positive (happiness, peacefulness) and negative (sadness, fear) emotions are compromised in patients with bvFTD. The processing of negative musical emotions is the most difficult for these individuals.

RESUMEN Introducción: Múltiples estudios han revelado que los sujetos con la variante conductual de la demencia frontotemporal (bvFTD) tienen dificultades para reconocer señales emocionales en múltiples diferentes modalidades de procesamiento (p. ej., rostros, prosodia). Actualmente, existen pocos estudios que evalúen el reconocimiento de emociones musicales en esta población. El objetivo de esta investigación es evaluar la capacidad de los sujetos con bvFTD para reconocer estímulos musicales con emociones positivas y negativas, en comparación con sujetos sanos. Métodos: Se evaluó a 12 pacientes con bvFTD y 24 controles sanos mediante una prueba de reconocimiento de emociones musicales. Se reprodujeron aleatoriamente 56 fragmentos de música de piano, 14 para cada una de las emociones (felicidad, tristeza, miedo y tranquilidad). Resultados: En los pacientes con bvFTD, se observó una media de respuestas correctas de 23,6 (42,26%), en contraste con los sujetos de control, quienes obtuvieron un promedio de respuestas correctas de 36,3 (64,8%). Se encontraron diferencias estadísticamente significativas para cada una de las emociones musicales evaluadas y en la puntuación total de la prueba (p < 0,01). El análisis intragrupal mostró una mayor dificultad en ambos grupos para el reconocimiento de emociones musicales negativas (tristeza, miedo), y los sujetos con bvFTD son los que mostraron peor desempeño. Conclusiones: Nuestros resultados indican que el reconocimiento de estímulos musicales con emociones positivas (felicidad, tranquilidad) y negativas (tristeza, miedo) se ve afectado en pacientes con bvFTD. Las emociones musicales negativas son las más difíciles de reconocer para estos pacientes.

Assessment of judgment ability in a Brazilian sample of patients with mild cognitive impairment and dementia / Avaliação da capacidade de julgamento em uma amostra brasileira de pacientes com comprometimento cognitivo leve e demência

ABSTRACT. Judgment is the ability to make sound decisions after consideration of relevant information, possible solutions, likely outcomes, and contextual factors. Loss of judgment is common in patients with mild cognitive impairment (MCI) and dementia. The Test of Practical Judgment (TOP-J) evaluates practical judgment in adults and the elderly, with 15- and 9-item versions that require individuals to listen to scenarios about everyday problems and report their solutions. Objective: Adaptation of TOP-J for a Brazilian sample, preparation of a reduced version and verification of the accuracy of both. Methods: Eighty-five older adults, including 26 with MCI, 20 with Alzheimer's disease (AD), 15 with frontotemporal dementia behavioral variant (FTDbv) and 24 controls, underwent neuropsychological assessment including the Brazilian adaptation of the TOP-J (TOP-J-Br). Results: On both TOP-J-Br versions, controls outperformed MCI, AD and FTDbv patients (p<0.001) and MCI outperformed AD and FTDbv (p<0.001). For the TOP-J/15-Br, the best cutoff for distinguishing controls and patients had a sensitivity of 91.7%, specificity of 59.0% and area under the curve of 0.8. For the TOP-J/9-Br, the best cutoff for distinguishing controls and patients had a sensitivity of 79.9%, specificity of 72.1% and area under the curve of 0.82. Conclusion: The TOP-J/15-Br, and particularly the TOP-J/9-Br, showed robust psychometric properties and the potential for clinical utility in Brazilian older adults at various stages of neurodegenerative cognitive decline.

RESUMO. Julgamento é a capacidade de tomar decisões acertadas, após considerar informações relevantes disponíveis, soluções possíveis, resultados prováveis ​​e fatores contextuais. A perda de julgamento é comum em pacientes com comprometimento cognitivo leve (CCL) e demência. O Teste de Julgamento Prático (TOP-J) avalia o julgamento prático em adultos e idosos, em versões de 15 e 9 itens, que exigem que os indivíduos ouçam cenários sobre problemas cotidianos e relatem suas soluções. Objetivo: Adaptação do TOP-J para amostra brasileira, elaboração de uma versão reduzida e verificação da acurácia de ambas. Métodos: Oitenta e cinco idosos, incluindo 26 com CCL, 20 com doença de Alzheimer (DA), 15 com variante comportamental de demência frontotemporal (DFTvc) e 24 controles, foram submetidos à avaliação neuropsicológica, incluindo a adaptação brasileira do TOP-J (TOP-J-Br). Resultados: Nas duas versões do TOP-J-Br, os controles superaram os CCL, DA e DFTvc (p<0,001) e o grupo CCL superou os grupos DA e DFTvc (p<0,001). Para o grupo TOP-J/15-Br, o melhor ponto de corte para diferenciação entre controles e pacientes apresentou sensibilidade de 91,7, especificidade de 59,0 e área sob a curva de 0,8. Para o TOP-J/9-Br, o melhor ponto de corte para diferenciação entre controles e pacientes teve sensibilidade de 79,9, especificidade de 72,1 e área sob a curva de 0,82. Conclusão: O TOP-J/15-Br, e particularmente o TOP-J/9-Br, mostraram propriedades psicométricas robustas e o potencial de utilidade clínica em idosos brasileiros em vários estágios de declínio cognitivo neurodegenerativo.

Recognition of musical emotions in the behavioral variant of frontotemporal dementia.

INTRODUCTION: Multiple investigations have revealed that patients with behavioral variant of frontotemporal dementia (bvFTD) experience difficulty recognizing emotional signals in multiple processing modalities (e.g., faces, prosody). Few studies have evaluated the recognition of musical emotions in these patients. This research aims to evaluate the ability of subjects with bvFTD to recognize musical stimuli with positive and negative emotions, in comparison with healthy subjects. METHODS: bvFTD (n=12) and healthy control participants (n=24) underwent a test of musical emotion recognition: 56 fragments of piano music were randomly reproduced, 14 for each of the emotions (happiness, sadness, fear, and peacefulness). RESULTS: In the subjects with bvFTD, a mean of correct answers of 23.6 (42.26%) was observed in contrast to the control subjects, where the average number of correct answers was 36.3 (64.8%). Statistically significant differences were found for each of the evaluated musical emotions and in the total score on the performed test (P<.01). The within-group analysis showed greater difficulty for both groups in recognizing negative musical emotions (sadness, fear), with the subjects with bvFTD exhibiting worse performance. CONCLUSIONS: Our results indicate that the recognition of musical stimuli with positive (happiness, peacefulness) and negative (sadness, fear) emotions are compromised in patients with bvFTD. The processing of negative musical emotions is the most difficult for these individuals.

Swallowing in behavioral variant frontotemporal dementia / Deglutição na variante comportamental da demência frontotemporal

ABSTRACT Background: Swallowing and feeding problems may occur with the progression of behavioral variant frontotemporal dementia (bvFTD) and can impair the anticipatory and oral preparatory phases of swallowing. Objective: To characterize swallowing problems and the feeding situation of patients with bvFTD and to correlate the swallowing problems with functionality, executive functions, cognitive and behavioral features. Methods: Consecutive outpatients with bvFTD in mild, moderate and severe dementia stages were recruited along with their caregivers. Patients and caregivers were screened with the following scales: "Mini-Mental State Examination", "Severe Mini-Mental State Examination", "FTLD-modified Clinical Dementia Rating", "Neuropsychiatric Inventory", "Frontal Assessment Battery", "Index of Independence in Activities of Daily Living", "Swallowing Rating Scale" and "Assessment of Feeding and Swallowing Difficulties in Dementia". Results: Overall, thirty patients with bvFTD were included along with their caregivers. Patients with bvFTD showed feeding and swallowing difficulties such as: messy to eat, passivity, coughing and choking, difficulty with some food consistencies and with specific food. Swallowing problems in bvFTD correlated with impaired functionality (p<0.05) and cognition (p<0.05), executive dysfunction (p<0.01) and behavioral features (p<0.01). Caregivers had great difficulty in managing the feeding situation during mealtime, with different characteristics in each dementia stage. Conclusion: Patients with bvFTD had inappropriate speed eating, passivity, coughing and choking starting in the mild dementia stage, and these problems worsen in the severe stage. Such difficulties affected caregiver performance during mealtime. The correlations indicated that swallowing difficulties tend to follow cognitive and behavioral decline in patients with bvFTD.

RESUMO Introdução: Os problemas na situação de alimentação e deglutição podem ocorrer com a progressão da variante comportamental da demência frontotemporal (DFT-vc) e alterar as fases antecipatória e preparatória oral da deglutição. Objetivo: Caracterizar os problemas de deglutição e a situação de alimentação de pacientes com DFT-vc e correlacionar os problemas de deglutição com a funcionalidade, funções executivas, aspectos cognitivos e comportamentais. Métodos: Foram recrutados pacientes ambulatoriais com DFT-vc nas fases leve, moderada e grave da demência, e seus respectivos cuidadores. Os pacientes e cuidadores foram avaliados com as escalas: "Mini-Exame do Estado Mental", "Mini-Exame do Estado Mental Grave", "Escala de Avaliação Clínica da Demência Modificada - DFT", "Inventário Neuropsiquiátrico", "Bateria de Avaliação Frontal", "Índice de Independência nas Atividades da Vida Diária", "Escala Funcional de Avaliação da Deglutição" e "Avaliação das Dificuldades de Alimentação e Deglutição na Demência". Resultados: Foram incluídos 30 pacientes com DFT-vc, e seus cuidadores. Pacientes com DFT-vc apresentaram dificuldades de alimentação e deglutição como: confusão na alimentação, passividade, tosse e asfixia, dificuldades com algumas consistências alimentares e alimentos específicos. Problemas de deglutição na DFT-vc correlacionaram-se com funcionalidade prejudicada (p<0,05) e cognição (p<0,05), disfunção executiva (p<0,01) e características comportamentais (p<0,01). Os cuidadores tiveram grande dificuldade em gerenciar a situação de alimentação diante de diferentes problemas em cada fase da demência. Conclusão: Pacientes com DFT-vc apresentaram velocidade de alimentação inapropriada, passividade, tosse e engasgos já na fase leve da doença, com piora na fase grave. As correlações indicaram que as alterações de deglutição tendem a seguir o declínio cognitivo e comportamental na DFT-vc.

Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing "where" by "what" / Passando de demências neurodegenerativas para proteinopatias cognitivas, substituindo "onde" por "o que"

ABSTRACT. Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detected. Neurodegenerative diseases can be produced by more than one abnormal protein and each proteinopathy can determine different clinical phenotypes. Specific biomarkers have now been linked to certain molecular pathologies in live patients. In 2016, a new biomarker-based classification, currently only approved for research in Alzheimer's disease, was introduced. It is based on the evaluation three biomarkers: amyloid (A) detected on amyloid-PET or amyloid- beta 42 assay in CSF; tau (T) measured in CSF as phosphorylated tau or on tau PET imaging; and neuronal injury/neurodegeneration (N), detected by total T-tau in CSF, FDG PET hypometabolism and on MRI brain scan. Results of clinical research using the ATN biomarkers at FLENI, a Neurological Institute in Buenos Aires, Argentina have, since 2011, contributed to ongoing efforts to move away from the concept of neurodegenerative dementias and more towards one of cognitive proteinopathies. Today, clinical diagnosis in dementia can only tell us "where" abnormal tissue is found but not "what" molecular mechanisms are involved.

RESUMO. As demências neurodegenerativas foram descritas com base em seu fenótipo, em relação à degeneração seletiva que ocorre em um sistema neuroanatômico específico. Mais recentemente, no entanto, o termo proteinopatia foi introduzido para descrever doenças nas quais uma ou mais proteínas alteradas podem ser detectadas. As doenças neurodegenerativas podem ser produzidas por mais de uma proteína anormal e cada proteinopatia pode determinar diferentes fenótipos clínicos. Biomarcadores específicos já foram associados a certas patologias moleculares em pacientes vivos. Em 2016, uma nova classificação baseada em biomarcadores, atualmente aprovada apenas para pesquisas na doença de Alzheimer, foi introduzida. É baseado na avaliação de três biomarcadores: amiloide (A) detectado no ensaio amiloide-PET ou amiloide-beta 42 no LCR; tau (T) medida no LCR como tau fosforilada ou em imagem de tau PET; e lesão/neurodegeneração neuronal (N), detectada por T-tau total no LCR, hipometabolismo FDG PET e pela ressonância magnética. Os resultados de pesquisas clínicas usando os biomarcadores ATN no FLENI, um Instituto Neurológico de Buenos Aires, Argentina, desde 2011, contribuíram para os esforços contínuos para se afastar do conceito de demência neurodegenerativa e mover-se mais em direção às proteinopatias cognitivas. Hoje, o diagnóstico clínico da demência só pode nos dizer "onde" o tecido anormal é encontrado, mas não "quais" mecanismos moleculares estão envolvidos.

Genetics of dementia: insights from Latin America / Genética das demências: percepção a partir da América Latina

ABSTRACT. Alzheimer's disease (AD) and frontotemporal dementia (FTD) are neurodegenerative disorders that result in a significant burden to both patients and caregivers. By 2050, the number of people with dementia in Latin America will increase 4-fold. A deep understanding of the relevant genetic factors of AD and FTD is fundamental to tackle this reality through prevention. A review of different genetic variants that cause AD or FTD in Latin America was conducted. We searched Medline and PubMed databases using the keywords "Alzheimer's disease," "frontotemporal dementia," "mutation," "America," and "Latin America," besides specific Latin American countries. Forty-five items were chosen and analyzed. PSEN1 mutations are the commonest cause of genetic early-onset Alzheimer's disease (EOAD), followed by PSEN2 and APP mutations. Genetic FTD can be mainly explained by GRN and MAPT mutations, as well as C9orf72 G4C2 repeat expansion. APOE ε4 can modify the prevalence and incidence of late-onset Alzheimer's disease (LOAD), in addition to the cognitive performance in affected carriers.

RESUMO. A doença de Alzheimer (DA) e a demência frontotemporal (DFT) são distúrbios neurodegenerativos que causam uma sobrecarga significativa para pacientes e cuidadores. Em 2050, o número de pessoas com demência na América Latina aumentará 4 vezes. Uma compreensão profunda dos fatores genéticos relevantes da DA e da DFT é fundamental para enfrentar essa realidade por meio da prevenção. Foi realizada uma revisão de diferentes variantes genéticas que causam a DA ou a DFT na América Latina. Pesquisamos os bancos de dados Medline e PubMed usando as palavras-chave "doença de Alzheimer", "demência frontotemporal", "mutação", "América" e "América Latina", além de países latino-americanos específicos. Quarenta e cinco itens foram escolhidos e analisados. As mutações do PSEN1 são a causa mais comum da doença de Alzheimer genética de início precoce (DAIP), seguida pelas mutações do PSEN2 e da APP. A DFT genética pode ser explicada principalmente por mutações no GRN, MAPT e expansões repetidas da C9orf72 G4C2. O APOE ε4 pode modificar a prevalência e a incidência da doença de Alzheimer de início tardio (DAIT), mas também o desempenho cognitivo em portadores afetados.