Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category "probable 4R-tauopathy" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD). OBJECTIVES: To investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns. METHODS: Thirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18 F]fluorodeoxyglucose and [11 C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group. RESULTS: Eleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata. CONCLUSIONS: The 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.

Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [18F]FDG-PET/MRI study.

BACKGROUND: Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. OBJECTIVE: To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). METHODS: Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. RESULTS: Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Gray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. CONCLUSION: Retired soccer players had reduced rBGM and GM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

ANTECEDENTES: Jogadores profissionais de futebol estão expostos a impactos cranianos repetitivos e ao risco de desenvolver encefalopatia traumática crônica. OBJETIVO: Avaliar o metabolismo glicolítico cerebral regional (MGCr) e o volume de substância cinzenta (vSC) em jogadores de futebol aposentados (JFAs). MéTODOS: Jogadores de futebol aposentados masculinos e controles pareados por idade e sexo foram incluídos prospectivamente entre 2017 e 2019. Foram realizadas avaliações neurológica e neuropsicológica, ressonância magnética (RM) e [18F]FDG-PET cerebrais (3.0-Tesla PET/RM). As imagens foram analisadas visualmente por um neurorradiologista e um médico nuclear cegos ao grupo de cada participante. O metabolismo glicolítico cerebral regional e o vSC foram avaliados através do programa SPM8. Os grupos foram comparados através de testes estatísticos apropriados disponíveis em SPM8 e R, de acordo com a distribuição e o tipo dos dados. RESULTADOS: Dezenove JFAs (mediana [IIQ]: 62 [50­64.5] anos) e 20 controles (60 [48­73] anos) foram incluídos. Os JFAs tiveram pior desempenho no mini-exame do estado mental e nos testes de dígitos, desenho do relógio, fluência verbal e fluência semântica e apresentaram MGCr significativamente reduzido no polo temporal e no giro temporal médio anterior esquerdos. Fluência semântica (animais) apresentou correlação positiva com MGCr no hipocampo direito, no polo temporal esquerdo e no aspecto posterior do giro temporal médio esquerdo. Menor vSC foi observado nas mesmas regiões, porém este achado não sobreviveu à correção para comparações múltiplas. Análise individual do [18F]FDG-PET cerebral revelou sete JFAs com claro hipometabolismo nas faces medial e lateral dos lobos temporais, nos lobos frontais e nas regiões temporoparietais. Os JFAs apresentaram ainda maior prevalência de anormalidades do septo pelúcido. CONCLUSãO: Os JFAs apresentam MGCr e vSC reduzidos nos lobos temporais, além de anormalidades do septo pelúcido, achados possivelmente relacionados a impactos cranianos repetitivos.

Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [18F]FDG-PET/MRI study / Metabolismo glicolítico cerebral e volume de substância cinzenta em jogadores de futebol profissionais aposentados: um estudo transversal de [18F]FDG-PET/RM

Abstract Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. Results Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Cray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. Conclusion Retired soccer players had reduced rBCM and CM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

Resumo Antecedentes Jogadores profissionais de futebol estão expostos a impactos cranianos repetitivos e ao risco de desenvolver encefalopatia traumática crônica. Objetivo Avaliar o metabolismo glicolítico cerebral regional (MCCr) e o volume de substância cinzenta (vSC) em jogadores de futebol aposentados (JFAs). Métodos Jogadores de futebol aposentados masculinos e controles pareados por idade e sexo foram incluídos prospectivamente entre 2017 e 2019. Foram realizadas avaliações neurológica e neuropsicológica, ressonância magnética (RM) e [18F]FDG-PET cerebrais (3.0-Tesla PET/RM). As imagens foram analisadas visualmente por um neurorradiologista e um médico nuclear cegos ao grupo de cada participante. O metabolismo glicolítico cerebral regional e o vSC foram avaliados através do programa SPM8. Os grupos foram comparados através de testes estatísticos apropriados disponíveis em SPM8 e R, de acordo com a distribuição e o tipo dos dados. Resultados Dezenove JFAs (mediana [IIQ]: 62 [50-64.5] anos) e 20 controles (60 [48-73] anos) foram incluídos. Os JFAs tiveram pior desempenho no mini-exame do estado mental e nos testes de dígitos, desenho do relógio, fluência verbal e fluência semântica e apresentaram MCCr significativamente reduzido no polo temporal e no giro temporal médio anterior esquerdos. Fluência semântica (animais) apresentou correlação positiva com MCCr no hipocampo direito, no polo temporal esquerdo e no aspecto posterior do giro temporal médio esquerdo. Menor vSC foi observado nas mesmas regiões, porém este achado não sobreviveu à correção para comparações múltiplas. Análise individual do [18F]FDG-PET cerebral revelou sete JFAs com claro hipometabolismo nas faces medial e lateral dos lobos temporais, nos lobos frontais e nas regiões temporoparietais. Os JFAs apresentaram ainda maior prevalência de anormalidades do septo pelúcido. Conclusão Os JFAs apresentam MCCr e vSC reduzidos nos lobos temporais, além de anormalidades do septo pelúcido, achados possivelmente relacionados a impactos cranianos repetitivos.

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.

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.

Normal pressure hydrocephalus: an update.

Normal pressure hydrocephalus (NPH) has been a topic of debate since its introduction in publications. More frequent in the elderly population, it is characterized by gait disturbance, urinary urge incontinence and cognitive decline. Therefore, it is a clinical-radiological entity with relatively common findings for the age group, which together may have greater specificity. Therefore, its diagnosis must be careful for an adequate selection of patients for treatment with ventricular shunt, since the symptoms are potentially reversible. The tap test has a high positive predictive value as a predictor of therapeutic response, but a negative test does not exclude the possibility of treatment. Scientific efforts in recent years have been directed towards a better understanding of NPH and this narrative review aims to compile recent data from the literature in a didactic way for clinical practice.

From clinical phenotype to proteinopathy: molecular neuroimaging in neurodegenerative dementias.

Neurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is 18F-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism. The pattern of regional hypometabolism provides neuroanatomical information on the neurodegenerative process, which, in turn, has a good specificity for each type of proteinopathy. FDG is very useful in the differential diagnosis of neurodegenerative dementias through the regional pattern of involvement, including dementia with Lewy bodies and the spectrum of frontotemporal dementia. More recently, radiotracers with specific ligands to some of the pathological proteins have been developed. Pittsburgh compound B (PIB) labeled with 11C and the ligands that use 18F (florbetapir, florbetaben and flutemetamol) are the most used radiotracers for the detection of insoluble ß-amyloid peptide in Alzheimer's disease (AD). A first generation of ligands for tau protein has been developed, but it has some affinity for other non-tau protein aggregates. A second generation has the advantage of having a higher affinity for hyperphosphorylated tau protein, including in primary tauopathies.

Translation, cross-cultural adaptation, and validity of the Brazilian version of the Cognitive Function Instrument.

Subjective cognitive decline (SCD) is defined as a self-perception of a progressive cognitive impairment, which is not detected objectively through neuropsychological tests. The Alzheimer's Disease Cooperative Study developed the Cognitive Function Instrument (CFI) to evaluate individuals with SCD. The CFI consists of two versions, namely, a self-report and a partner report. Objective: This study aimed to translate CFI into Brazilian Portuguese, perform a cross-cultural adaptation, and validate the Brazilian version. Methods: The translation and transcultural adaptation process consisted of six stages, and the preliminary version was answered by a sample of individuals recruited among the patients' caregivers from a cognitive neurology outpatient clinic. Finally, the final Brazilian version of the CFI was applied to a sample of nondemented older adults to validate the instrument, which was divided into with and without SCD, according to the answer "yes" for the question: "Do you feel like your memory is becoming worse?". Results: The final version of CFI showed a high level of acceptability as an assessment tool in nondemented older adults. Participants with SCD had higher scores in the CFI self-report compared with those without complaints. In the receiver operating characteristic curve analysis, the area under the curve of the CFI self-report was 0.865 (95% confidence interval 0.779-0.951), and the cutoff score of 2.0 was the one that best distinguished the SCD group from the control group, with a sensitivity of 73.3% and a specificity of 81.5%. Conclusions: CFI proved to be an instrument with good accuracy and easy applicability to identify older adults with SCD.

O declínio cognitivo subjetivo (DCS) é definido como uma autopercepção de um comprometimento cognitivo progressivo, não detectado objetivamente por meio de testes neuropsicológicos. O Alzheimer's Disease Cooperative Study desenvolveu o instrumento de função cognitiva (IFC) para avaliar indivíduos com DCS. O IFC existe em duas versões, uma do paciente e outra do acompanhante. Objetivo: O objetivo deste estudo foi traduzir para o português brasileiro, fazer uma adaptação transcultural e validar a versão brasileira do IFC. Métodos: O processo de tradução e adaptação transcultural consistiu em seis etapas, e a versão preliminar foi respondida por uma amostra de voluntários recrutados entre os cuidadores de pacientes de um ambulatório de Neurologia Cognitiva. Por fim, a versão brasileira final do IFC foi aplicada a idosos sem demência, que foram divididos naqueles com e sem DCS de acordo com a resposta "sim" à questão: "Você sente que a sua memória está piorando?". Resultados: A versão final do IFC mostrou alto nível de aceitabilidade como ferramenta de avaliação em idosos sem demência. Os participantes com DCS tiveram pontuações mais altas na versão do paciente em comparação com aqueles sem queixas. Nas análises da curva característica de operação do receptor (ROC), a área sobre a curva da versão do paciente foi de 0,865 (intervalo de confiança [IC95%] 0,779­0,951) e a pontuação de corte de 2,0 foi a que melhor distinguiu o grupo com DCS dos controles, com sensibilidade de 73,3% e especificidade de 81,5%. Conclusões: O IFC mostrou-se um instrumento de boa acurácia e de fácil aplicabilidade para identificar idosos com DCS.

Normal pressure hydrocephalus: an update / Hidrocefalia de pressão normal: uma atualização

ABSTRACT Normal pressure hydrocephalus (NPH) has been a topic of debate since its introduction in publications. More frequent in the elderly population, it is characterized by gait disturbance, urinary urge incontinence and cognitive decline. Therefore, it is a clinical-radiological entity with relatively common findings for the age group, which together may have greater specificity. Therefore, its diagnosis must be careful for an adequate selection of patients for treatment with ventricular shunt, since the symptoms are potentially reversible. The tap test has a high positive predictive value as a predictor of therapeutic response, but a negative test does not exclude the possibility of treatment. Scientific efforts in recent years have been directed towards a better understanding of NPH and this narrative review aims to compile recent data from the literature in a didactic way for clinical practice.

RESUMO A hidrocefalia de pressão normal (HPN) é tema de debate desde sua introdução na literatura. Mais frequente na população idosa, caracteriza-se por distúrbio de marcha, urge-incontinência urinária e declínio cognitivo. Portanto, trata-se de uma entidade clínico-radiológica com achados relativamente comuns para a faixa etária, que em conjunto, podem ter maior especificidade. Sendo assim, seu diagnóstico deve ser criterioso para uma adequada seleção de pacientes para tratamento com a derivação ventricular, uma vez que os sintomas são potencialmente reversíveis. O tap test possui valor preditivo positivo alto preditor de resposta terapêutica, mas um teste negativo não exclui a possibilidade de tratamento. Esforços científicos nos últimos anos têm sido direcionados para melhor entendimento da HPN e essa revisão narrativa se propõe a compilar dados recentes da literatura de forma didática para a prática clínica.

From clinical phenotype to proteinopathy: molecular neuroimaging in neurodegenerative dementias / Do fenótipo clínico à proteinopatia: a neuroimagem molecular nas demências neurodegenerativas

ABSTRACT Neurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is 18F-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism. The pattern of regional hypometabolism provides neuroanatomical information on the neurodegenerative process, which, in turn, has a good specificity for each type of proteinopathy. FDG is very useful in the differential diagnosis of neurodegenerative dementias through the regional pattern of involvement, including dementia with Lewy bodies and the spectrum of frontotemporal dementia. More recently, radiotracers with specific ligands to some of the pathological proteins have been developed. Pittsburgh compound B (PIB) labeled with 11C and the ligands that use 18F (florbetapir, florbetaben and flutemetamol) are the most used radiotracers for the detection of insoluble β-amyloid peptide in Alzheimer's disease (AD). A first generation of ligands for tau protein has been developed, but it has some affinity for other non-tau protein aggregates. A second generation has the advantage of having a higher affinity for hyperphosphorylated tau protein, including in primary tauopathies.

RESUMO As demências neurodegenerativas caracterizam-se pelo acúmulo anormal de proteínas mal dobradas. Entretanto, os seus critérios diagnósticos ainda se baseiam no fenótipo clínico. O desenvolvimento de biomarcadores permitiu a detecção in vivo do processo fisiopatológico. O objetivo deste artigo é fazer uma revisão não-sistemática sobre o papel da neuroimagem molecular como biomarcador. A neuroimagem molecular baseia-se no uso de radiotraçadores para aquisição da imagem. O mais usado no PET é o 18F-fluorodeoxiglicose (FDG), com o qual é possível estudar o metabolismo regional de glicose cerebral. O padrão de hipometabolismo regional fornece uma informação neuroanatômica do processo neurodegenerativo que, por sua vez, tem uma boa especificidade para cada tipo de proteinopatia. O PET-FDG é muito útil no diagnóstico diferencial das demências neurodegenerativas através do padrão de acometimento regional, incluindo a demência com corpos de Lewy e o espectro das demências frontotemporais. Mais recentemente, radiotraçadores com ligantes específicos a algumas das proteínas patológicas têm sido desenvolvidos. O composto B de Pittsburgh (PIB) com 11C e os ligantes dos que usam 18F (florbetapir, florbetaben e flutemetamol) são os radiotraçadores mais usados para a detecção de peptídeo β-amiloide insolúvel na doença de Alzheimer (DA). Uma primeira geração de ligantes para proteína tau foi desenvolvida, mas apresenta alguma afinidade a outros agregados proteicos não-tau. Uma segunda geração tem a vantagem de apresentar uma maior afinidade à proteína tau hiperfosforilada, incluindo nas taupatias primárias.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study

Objective: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study.

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach. Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech-language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls. Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical-semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A- group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A- group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R 2 = 0.2326), middle (0.0054, R 2 = 0.2376), and superior temporal gyri (p = 0.0066, R 2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R 2 = 0.3685), the inferior (p = 0.0004, R 2 = 0.3537), and the middle temporal gyri (p = 0.0001, R 2 = 0.3993). Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.

Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series.

OBJECTIVE: To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center. METHODS: We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. RESULTS: Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001). CONCLUSION: In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.

Understanding brain resilience in superagers: a systematic review.

PURPOSE: Superagers are older adults presenting excellent memory performance that may reflect resilience to the conventional pathways of aging. Our contribution aims to shape the evidence body of the known distinctive biomarkers of superagers and their connections with the Brain and Cognitive Reserve and Brain Maintenance concepts. METHODS: We performed a systematic literature search in PubMed and ScienceDirect with no limit on publication date for studies that evaluated potential biomarkers in superagers classified by validated neuropsychological tests. Methodological quality was assessed using the QUADAS-2 tool. RESULTS: Twenty-one studies were included, the majority in neuroimaging, followed by histological, genetic, cognition, and a single one on blood plasma analysis. Superagers exhibited specific regions of cortical preservation, rather than global cortical maintenance, standing out the anterior cingulate and hippocampus regions. Both superagers and controls showed similar levels of amyloid deposition. Moreover, the functional oscillation patterns in superagers resembled those described in young adults. Most of the quality assessment for the included studies showed medium risks of bias. CONCLUSION: This systematic review supports selective cortical preservation in superagers, comprehending regions of the default mode, and salience networks, overlapped by stronger functional connectivity. In this context, the anterior cingulate cortex is highlighted as an imaging and histologic signature of these subjects. Besides, the biomarkers included pointed out that the Brain and Cognitive Reserve and Brain Maintenance concepts are independent and complementary in the superagers' setting.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study.

OBJECTIVE: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. METHODS: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). RESULTS: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. CONCLUSIONS: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital.

BACKGROUND: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. OBJECTIVE: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. METHODS: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. RESULTS: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). CONCLUSIONS: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital / Consultas neurológicas e diagnósticos em um grande hospital universitário dedicado a COVID-19

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

RESUMO Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomas neurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doenças neurológicas prévias podem exigir tratamento especial e estar associadas a piores desfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmente pouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitar consultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com 900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico de COVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas as interconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foram analisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dados disponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionais conforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões de consenso. Após o diagnóstico, os neurologistas participaram da condução dos casos. Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) em pacientes internados por COVID-19 durante o período. Os principais diagnósticos neurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%), doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornos neuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomas leves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em um hospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetar o desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecer sintomas neurológicos. Os neurologistas são membros importantes da equipe médica no atendimento hospitalar à COVID-19.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital / Consultas neurológicas e diagnósticos em um grande hospital universitário dedicado a COVID-19

Background: More than one-third of COVID-19 patients present neurological symptomsranging from anosmia to stroke and encephalopathy. Furthermore, pre-existingneurological conditions may require special treatment and may be associated with worseoutcomes. Notwithstanding, the role of neurologists in COVID-19 is probablyunderrecognized. Objective: The aim of this study was to report the reasons forrequesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital dasClínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bedCOVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosiswas confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurologyconsultations between March 23rd and May 23rd, 2020 were analyzed. Neurologistsperformed the neurological exam, assessed all available data to diagnose theneurological condition, and requested additional tests deemed necessary. Difficultdiagnoses were established in consensus meetings. After diagnosis, neurologists wereinvolved in the treatment. Results: Neurological consultations were requested for 89 outof 1,208 (7.4%) inpatient COVID admissions during that period. Main neurologicaldiagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurologicaldiseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brainlesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Mostneurological consultations in a COVID-19-dedicated hospital were requested for severeconditions that could have an impact on the outcome. First-line doctors should be able torecognize neurological symptoms; neurologists are important members of the medicalteam in COVID-19 hospital care.

Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomasneurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doençasneurológicas prévias podem exigir tratamento especial e estar associadas a pioresdesfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmentepouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitarconsultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade deMedicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico deCOVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas asinterconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foramanalisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dadosdisponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionaisconforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões deconsenso. Após o diagnóstico, os neurologistas participaram da condução dos casos.Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) empacientes internados por COVID-19 durante o período. Os principais diagnósticosneurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%),doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornosneuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomasleves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em umhospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetaro desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecersintomas neurológicos. Os neurologistas são membros importantes da equipe médica noatendimento hospitalar à COVID-19.