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Objective Teleneuropsychology (teleNP) could potentially expand access to services for patients who are confined, have limited personal access to healthcare, or live in remote areas. The emergence of the COVID-19 pandemic has significantly increased the use of teleNP for cognitive assessments. The main objective of these recommendations is to identify which procedures can be potentially best adapted to the practice of teleNP in Latin America, and thereby facilitate professional decision-making in the region. Method Steps taken to develop these recommendations included (1) formation of an international working group with representatives from 12 Latin American countries; (2) assessment of rationale, scope, and objectives; (3) formulation of clinical questions; (4) evidence search and selection; (5) evaluation of existing evidence and summary; and (6) formulation of recommendations. Levels of evidence were graded following the Oxford Centre for Evidence-Based Medicine system. Databases examined included PubMed, WHO-IRIS, WHO and PAHO-IRIS, Índice Bibliográfico Español en Ciencias de la Salud (IBCS), and LILACS. Results Working group members reviewed 18,400 titles and 422 abstracts and identified 19 articles meeting the criteria for level of evidence, categorization, and elaboration of recommendations. The vast majority of the literature included teleNP tests in the English language. The working group proposed a series of recommendations that can be potentially best adapted to the practice of teleNP in Latin America. Conclusions There is currently sufficient evidence to support the use of videoconferencing technology for remote neuropsychological assessments. These recommendations will likely contribute to the advancement of teleNP research and practice in the region.

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.

Introduction Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are frequent causes of dementia and, therefore, instruments for differential diagnosis between these two conditions are of great relevance. Objective To investigate the diagnostic accuracy of Addenbrooke’s Cognitive Examination-Revised (ACE-R) for differentiating AD from bvFTD in a Brazilian sample. Methods The ACE-R was administered to 102 patients who had been diagnosed with mild dementia due to probable AD, 37 with mild bvFTD and 161 cognitively healthy controls, matched according to age and education. Additionally, all subjects were assessed using the Mattis Dementia Rating Scale and the Neuropsychiatric Inventory. The performance of patients and controls was compared by using univariate analysis, and ROC curves were calculated to investigate the accuracy of ACE-R for differentiating AD from bvFTD and for differentiating AD and bvFTD from controls. The verbal fluency plus language to orientation plus name and address delayed recall memory (VLOM) ratio was also calculated. Results The optimum cutoff scores for ACE-R were 0.85. For the differential diagnosis between AD and bvFTD, a VLOM ratio of 3.05 showed an AUC of 0.816 (Cohen’s d = 1.151; p Conclusions The Brazilian ACE-R achieved a good diagnostic accuracy for differentiating AD from bvFTD patients and for differentiating AD and bvFTD from the controls in the present sample.

Introduction Few dementia incidence studies have been performed in Latin America. We aimed to provide the incidence of dementia in a Brazilian community-dwelling elderly population. Methods This study was conducted in urban and rural areas of Tremembe. The 520 participants without dementia at baseline were invited to participate in the follow-up. Results After a median follow-up of 5 years, the incidence rate of dementia was 26.1 per 1000 person-years (PY) (95% confidence interval = 18.7-36.6/1000PY). This rate increased exponentially with age (8.3/1000PY for 60- to 64-year-olds to 110.2/1000PY for ≥80-year-olds) and lower education (10.5/1000PY for > 8 years of education to 59.2/1000PY for illiterates). Higher dementia risk was found among individuals with cognitive impairment no dementia at baseline. Discussion The dementia incidence rate found was higher than in other countries in people under 65 years. Higher incidence in younger individuals is expected in developing countries probably due to low education and a high burden of cardiovascular diseases.

Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue.We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules - MAP2) changes in postmortem brain samples of individuals with Lewy body pathology.Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated.Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24).Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.Estudos dos efeitos da atividade física relataram melhora nos sintomas e na qualidade de vida de pacientes com doença de Parkinson (DP). Além disso, alterações morfológicas do cérebro após o exercício físico foram relatadas em modelos animais da DP. No entanto, essas mudanças relacionadas ao estilo de vida não foram avaliadas em tecido cerebralAvaliar a expressão de astrócitos, tirosina hidroxilase (TH) e a expressão de proteínas estruturais (neurofilamentos e microtúbulos — MAP2) por imuno-histoquímica, em amostras cerebraisAmostras com estágio de Braak para DP≥III, classificação neuropatológica, fornecidas pelo biobanco de estudos do envelhecimento foram classificadas em grupos ativos (n=12) e não ativos (n=12), de acordo com o estilo de vida (atividade física), e pareados por idade, sexo e estadiamento de Braak. Analisou-se a substância negra e gânglios da base.Idade, sexo e classificação para DP foram semelhantes (p=1,00). Observou-se maior expressão de TH no grupo ativo (p=0,04). Amostras de não ativos revelaram maior expressão de astrócitos no mesencéfalo (p=0,03) e nos gânglios da base (p=0,0004); MAP2 nos gânglios da base (p=0,003); os níveis de neurofilamentos foram maiores na substância negra (p=0,006).O estilo de vida ativo parece promover efeitos positivos no cérebro, mantendo a síntese de dopamina e a expressão estrutural de proteínas no sistema nigrostriatal e com diminuição da ativação de astrócitos em indivíduos com a mesma classificação neuropatológica para a DP.

Depression has been associated with dementia. This study aimed to verify if β-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study.We included 1013 deceased subjects submitted to autopsy (mean age=74.3±11.6 years, 49% men) in a community sample. β-amyloid burden was measured in all cases based on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for presence and density of neuritic plaques. Lifetime MDD was defined when at least one previous episode according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM (SCID). Depressive symptoms and cognitive impairment were determined using the depression item of the Neuropsychiatric Inventory (D-NPI0) and the Clinical Dementia Rating scale (CDR0.5) respectively.Lifetime MDD, late life depression (LLD) and current depressive symptoms were associated with cognitive impairment (p0.001). Additionally, neuritic plaques were associated with cognitive impairment (p0.001). Moderate or frequent neurite plaque density was not associated with MDD, LLD or current depressive symptoms in multiple logistic models adjusted for age, gender, and cognitive impairment.In this cross-sectional study, all neuropsychiatric and cognitive assessment were based on informant-report of deceased participants.Different clinical depictions of depression were associated with dementia in this large community sample of elderly individuals with multiethnic backgrounds. Notwithstanding, they were unrelated to β-amyloid pathology in the brain areas studied. The link between depression and dementia might be complex and determined by multiple factors.

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.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF. Fil: Parra, Mario Alfredo. Universidad Autónoma del Caribe; Colombia Fil: Baez, Sandra. Universidad de los Andes; Colombia Fil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gonzalez Campo, Cecilia. Universidad de San Andrés; Argentina Fil: Santamaría García, Hernando. Pontificia Universidad Javeriana; Colombia Fil: Aprahamian, Ivan. No especifíca; Fil: Bertolucci, Paulo. Universidade Federal de Sao Paulo; Brasil Fil: Bustin, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina Fil: Camargos Bicalho, Maria Aparecida. Universidade Federal de Minas Gerais; Brasil Fil: Cano Gutierrez, Carlos. Hospital Universitario San Ignacio; Colombia Fil: Caramelli, Paulo. Universidade Federal de Minas Gerais; Brasil Fil: Chaves, Marcia L. F.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Perez Cogram, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina Fil: Beber, Bárbara Costa. Universidade Federal do Rio Grande do Sul; Brasil Fil: Court, Felipe A.. Universidad Mayor; Chile Fil: de Souza, Leonardo Cruz. Universidade Federal de Minas Gerais; Brasil Fil: Custodio, Nilton. Peruvian Institute of Neurosciences; Perú Fil: Damian, Andres. Universidad de la República; Uruguay Fil: de la Cruz, Myriam. University of California; Estados Unidos Fil: Diehl Rodriguez, Roberta. Universidade de Sao Paulo; Brasil Fil: Dozzi Brucki, Sonia Maria. Universidade de Sao Paulo; Brasil Fil: Fajersztajn, Lais. Universidade de Sao Paulo; Brasil Fil: Farías, Gonzalo A.. Universidad de Chile; Chile Fil: De Felice, Fernanda G.. Universidade Federal do Rio de Janeiro; Brasil Fil: Ferrari, Raffaele. Colegio Universitario de Londres; Reino Unido Fil: Ferreira de Oliveira, Fabricio. Universidade de Sao Paulo; Brasil Fil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; Brasil Fil: Ferretti, Ceres. Universidade de Sao Paulo; Brasil Fil: Figueredo Balthazar, Marcio Luiz. Universidade Estadual de Campinas; Brasil Fil: Ferreira Frota, Norberto Anizio. Universidade de Fortaleza; Brasil Fil: Fuentes, Patricio. No especifíca; Fil: García, Adolfo Martín. Universidad Nacional de Cuyo; Argentina. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garcia, Patricia J.. Cayetano Heredia University; Perú Fil: de Gobbi Porto, Fábio Henrique. Universidade de Sao Paulo; Brasil Fil: Duque Peñailillo, Lissette. Ecuadorian Dementia Association; Ecuador Fil: Engler, Henry Willy. Universidad de la República; Uruguay Fil: Maier, Irene. Universidad de Chile; Chile Fil: Mata, Ignacio F.. University of Pittsburgh; Estados Unidos Fil: González Billault, Christian. Universidad de Chile; Chile Fil: Lopez, Oscar L.. University of Pittsburgh; Estados Unidos Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Nitrini, Ricardo. Universidade de Sao Paulo; Brasil Fil: Quiroz, Yakeel T.. Harvard Medical School; Estados Unidos Fil: Guerrero Barragan, Alejandra. Universidad de la Sabana; Colombia Fil: Huepe, David. Universidad Adolfo Ibañez; Chile Fil: Pio, Fabricio Joao. Hospital Governador Celso Ramos; Brasil Fil: Suemoto, Claudia Kimie. Universidade de Sao Paulo; Brasil Fil: Kochhann, Renata. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Kochen, Sara Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Kumfor, Fiona. University of Western Sydney; Australia Fil: Lanata, Serggio. University of California; Estados Unidos Fil: Miller, Bruce. University of California; Estados Unidos Fil: Lessa Mansur, Leticia. Universidade de Sao Paulo; Brasil Fil: Lie Hosogi, Mirna. Universidade de Sao Paulo; Brasil Fil: Lillo, Patricia. Universidad de Chile; Chile Fil: Llibre Guerra, Jorge. University of California; Estados Unidos Fil: Lira, David. Peruvian Institute of Neurosciences; Perú Fil: Lopera, Francisco. Universidad de Antioquia; Colombia Fil: Comas, Adelina. No especifíca; Fil: Avila Funes, José Alberto. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; México Fil: Sosa, Ana Luisa. Instituto Nacional de Neurología y Neurocirugía; México Fil: Ramos, Claudia. University of California; Estados Unidos Fil: de Paula França Resende, Elisa. University of California; Estados Unidos Fil: Snyder, Heather M.. No especifíca; Fil: Tarnanas, Ioannis. University of California; Estados Unidos Fil: Yokoyama, Jenifer. University of California; Estados Unidos Fil: Llibre, Juan. Centro de Estudios de Alzheimer; Cuba Fil: Cardona Londoño, Juan Felipe. Universidad del Valle; Colombia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Possin, Kate. University of California; Estados Unidos Fil: Kosik, Kenneth. University of California; Estados Unidos Fil: Montesinos, Rosa. Peruvian Institute of Neurosciences; Perú Fil: Moguilner, Sebastian Gabriel. University of California; Estados Unidos Fil: Solis, Patricia Cristina Lourdes. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche; Argentina. Universidad de Buenos Aires; Argentina Fil: de Lucena Ferretti Rebustini, Renata Eloah. Universidade de Sao Paulo; Brasil Fil: Ramirez, Jeronimo Martin. No especifíca; Fil: Matallana, Diana. Pontificia Universidad Javeriana; Colombia Fil: Mbakile Mahlanza, Lingani. University of California; Estados Unidos Fil: Mendonça Marques Ton, Alyne. Universidade Federal do Rio de Janeiro; Brasil Fil: Melo Tavares, Ronnielly. Centro Universitario de Belo Horizonte.; Brasil Fil: Miotto, Eliane C.. Universidade de Sao Paulo; Brasil Fil: Muniz-Terrera, Graciela. University of Edinburgh; Reino Unido Fil: MuñozN evárez, Luis Arnoldo. University of California; Estados Unidos Fil: Orozco, David. Universidad Nacional del Sur; Argentina Fil: Okada de Oliveira, Maira. University of California; Estados Unidos Fil: Piguet, Olivier. University of Western Sydney; Australia Fil: Pintado Caipa, Maritza. University of California; Estados Unidos Fil: Piña Escudero, Stefanie Danielle. University of California; Estados Unidos Fil: Porcello Schilling, Lucas. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Rodrigues Palmeira, André Luiz. Hospital Ernesto Dornelles; Brasil Fil: Sanches Yassuda, Mônica. Universidade de Sao Paulo; Brasil Fil: Santacruz Escudero, Jose Manuel. Pontificia Universidad Javeriana; Colombia Fil: Serafim, Rodrigo Bernardo. Universidade Federal do Rio de Janeiro; Brasil Fil: Smid, Jerusa. Universidade de Sao Paulo; Brasil Fil: Slachevsky, Andrea. Universidad de Chile; Chile Fil: Serrano, Cecilia Mariela. No especifíca; Fil: Soto Añari, Marcio. Universidad Católica San Pablo; Perú Fil: Takada, Leonel Tadao. Universidade de Sao Paulo; Brasil Fil: Tenenholz Grinberg, Lea. Universidade de Sao Paulo; Brasil Fil: Teixeira, Antonio Lucio. Universidade Federal de Minas Gerais; Brasil Fil: Tonidandel Barbosa, Maira. Universidade Federal de Minas Gerais; Brasil Fil: Trépel, Dominic. Trinity College; Estados Unidos Fil: Ibañez, Agustin Mariano. Universidad Autónoma del Caribe; Colombia. Universidad Adolfo Ibañez; Chile. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Bipolar disorder (BD) is a severe and recurrent neuropsychiatric illness that causes high rates of disability, with onset frequently during adolescence and early adulthood 1. Devastating health and social consequences of BD are associated with the fact that the illness is often misdiagnosed, which leads to inappropriate or delayed treatments 2,3. Misdiagnosis is also a consequence of the fact that the etiology of BD still poorly understood. Disturbances in multiple systems have been proposed to play a role in BD pathophysiology, including metabolic, neuroendocrine and immune-inflammatory 4–6. Metabolic comorbidities are associated with BD burden, such as diabetes, obesity and cardiovascular diseases, supporting the role of systemic inflammation in BD 7–9. In two different meta-analysis, elevated peripheral levels (serum or plasma) of pro-inflammatory cytokines IL-4, IL-6, IL-10, and TNF-α were found in BD patients, when compared to controls 10,11. In a meta-analytic study comparing mood episodes, increased levels of peripheral IL-6 were found in mania. In addition, increased levels of TNF-α were found in mania and depression, and increased levels of IL-6 and C-reactive protein (CRP) were found in euthymia 12. CRP is an inflammatory factor related to acute immune response 13 that has been investigated previously in the blood of BD patients 14. Higher levels of CRP were also associated with cognitive dysfunction in BD 15. Cortisol is a glucocorticoid closely involved in inflammation and cytokine regulation 16. Increased cortisol levels in serum/plasma or urine have been found in BD, especially during mania and euthymia 17, supporting a contribution of the hypothalamic–pituitary–adrenal (HPA) axis in this disorder. Although several shreds of evidence from peripheral measures strongly support the role of inflammation and neuroendocrine changes in BD, the consequences of these systemic alterations to the brain and the potential presence of neuroinflammation still poorly understood. A recent meta-analysis conducted in BD post-mortem brains revealed important evidence of neuroinflammation regarding cell types and molecules involved 18. Among the addressed molecular parameters, the cytokines TNF-α, IL-1β, and IL-6 were found to be increased in the pre-frontal cortex of BD patients 19. For the purpose of this study, that meta-analysis revealed that the majority of the post-mortem studies in BD brains addressed frontal cortex. There has not been any study focusing on the same inflammatory and neuroendocrine factors in different brain regions. Furthermore, IL-17, CRP and cortisol have not been evaluated in post-mortem brain samples of BD patients. Here, we investigated different neuroinflammatory markers, including a panel of cytokines (IL-1β, IL-6, IL-10, IL-17A and TNF-α) and CRP, as well as cortisol levels in the hippocampus and anterior cingulate cortex (ACC) in post-mortem brains of BD subjects. These two brain regions have been consistently investigated and implicated in the pathophysiology via neuroimaging studies 20,21 and are morphologically and biochemically altered in BD showing volume reduction and glutamatergic abnormalities 22,23

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. 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. 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. 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.

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.

ObjectiveTo describe the postmortem neuropathologic findings of a patient with Kufor Rakeb syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment.MethodsA detailed neuropathologic analysis of the brain was performed. The patient had a genetically confirmed ATP13A2 homozygous missense mutation and died at age 38 years, which was 26 years after the onset of his symptoms.ResultsThe main brain neuropathologic findings were widespread neuronal and glial lipofuscin accumulation with no Lewy body–type inclusions and absence of α-synuclein–positive, tau-positive, β-amyloid–positive, and TDP-43 protein–positive pathologies. Sparse iron deposits were observed in several brain areas, but no obvious axonal spheroids were identified.DiscussionThis is to our knowledge the first KRS postmortem neuropathologic description. Iron deposits were found but not associated with increased axonal spheroids, as frequently observed in neurodegeneration with brain iron accumulation. ATP13A2 mutations have been described in patients with neuronal ceroid lipofuscinosis (CLN). Moreover, animal models with these mutations develop neurodegenerative disorders with CLN pathology. Therefore, our findings support that ATP13A2 mutations may be considered a genetic etiology of neuronal lipofuscinosis.

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

Made available in DSpace on 2022-04-29T08:46:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) BACKGROUND AND PURPOSE: Youthful memory performance in older adults may reflect an underlying resilience to the conventional pathways of aging. Subjects having this unusual characteristic have been recently termed “superagers.” This study aimed to explore the significance of imaging biomarkers acquired by 1H-MRS to characterize superagers and to differentiate them from their normal-aging peers. MATERIALS AND METHODS: Fifty-five patients older than 80 years of age were screened using a detailed neuropsychological protocol, and 25 participants, comprising 12 superagers and 13 age-matched controls, were statistically analyzed. We used state-of-the-art 3T 1H-MR spectroscopy to quantify 18 neurochemicals in the posterior cingulate cortex of our subjects. All 1H-MR spectroscopy data were analyzed using LCModel. Results were further processed using 2 approaches to investigate the technique accuracy: 1) comparison of the average concentration of metabolites estimated with Cramer-Rao lower bounds,20%; and 2) calculation and comparison of the weighted means of metabolites' concentrations. RESULTS: The main finding observed was a higher total N-acetyl aspartate concentration in superagers than in age-matched controls using both approaches (P ¼.02 and P ¼.03 for the weighted means), reflecting a positive association of total N-acetyl aspartate with higher cognitive performance. CONCLUSIONS: 1H-MR spectroscopy emerges as a promising technique to unravel neurochemical mechanisms related to cognitive aging in vivo and providing a brain metabolic signature in superagers. This may contribute to monitoring future interventional therapies to avoid or postpone the pathologic processes of aging. The Department of Radiology and Oncology Universidade de Sao Paulo Department of Neurology Universidade de Sao Paulo Division and Laboratory of Nuclear Medicine Department of Radiology and Oncology Hospital das Clinicas da Faculdade Medicina Universidade de Sao Paulo The National Hospital of Neurology and Neurosurgery University College London Department of Biostatistics Institute of Biosciences Universidade Estadual Paulista, Sao Paulo Department of Biostatistics Institute of Biosciences Universidade Estadual Paulista, Sao Paulo

Background: In the last 10 months, due to the Covid-19 pandemic, several studies have shown that health education and virtual support strategies for caregivers of patients with dementia, in the management of home care, can be viable. Low and middle income countries, in particular, have sought to use these means to reduce the daily burden of caregivers, through virtual meetings of education and support.Objectives: To present the feasibility of a pilot study on the use of a support action contemplated by the Caad Project–indirect costs of dementia–from HC-FMUSP.Methods: Observational study in which 93 caregivers were invited to participate in virtual meetings on a frequency of three times/week, lasting 1 h each.Results: Of the 93 invited family members, and after 3 months, 42 answered eight questions about the effectiveness of the action. High percentages of positive responses regarding program satisfaction ranged from 86 to 100%.Conclusion: This study showed results of a very simple intervention that suggests that it is possible to offer caregivers of patients with dementia a program that can be used in primary care, in order to understand the difficulty of caregivers in their daily care of patients with dementia, with daily management guidelines on a case-by-case basis, in addition to promoting the implementation of an education strategy about the importance of knowing, and recognizing anatomophysiological changes in the aging process and its implications for the rupture of the imaginary line that involves senescence and senility. This allows the caregiver to feel able to protect his patient and himself by preventing the emergence of common diseases in this age group. Further studies are needed to explore this type of non-pharmacological support.

IntroductionCOVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analysesWe will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and disseminationAll components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration numberRBR-8z7v5wc; Pre-results.

Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords “normal-pressure hydrocephalus” / “idiopathic normal-pressure hydrocephalus” / “secondary normal-pressure hydrocephalus” / “NPH” / “ventriculoperitoneal shunt”. The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH. RESUMO. A hidrocefalia de pressão normal (HPN) é uma síndrome potencialmente reversível marcada por ventrículos cerebrais alargados (ventriculomegalia), declínio cognitivo, apraxia da marcha e incontinência urinária. Revisar criticamente o conceito, a fisiopatologia, o diagnóstico e o tratamento da HPN idiopática e secundária. Os autores acessaram as bases de dados Medline e Pubmed entre janeiro de 2012 e dezembro de 2018, utilizando as palavras-chave “normal-pressure hydrocephalus” / “idiopathic normal-pressure hydrocephalus” / “secondary normal-pressure hydrocephalus” / “NPH” / “ventriculoperitoneal shunt”. A busca inicial resultou em 341 artigos. Após cuidadosa seleção, 54 estudos foram escolhidos e pesquisas adicionais foram incluídas durante o processo de elaboração do manuscrito. A HPN é uma importante causa de demência potencialmente reversível, quedas frequentes e infecção urinária recorrente em idosos. As características clínicas e de imagem da HPN podem ser incompletas ou inespecíficas, de modo que este se torna um diagnóstico difícil para médicos. Não raro uma avaliação por especialista é necessária, visando minimizar tratamentos cirúrgicos ineficazes. Avanços recentes advindos do uso não invasivo de ressonância magnética para quantificação do fluxo sanguíneo cerebral, em particular arterial spin-labeling (ASL), assim como a usual associação entre HPN e apneia obstrutiva do sono representam novos meios de entender e de tratar a HPN.

The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca’s area, might explain the preservation of repetition.

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination.Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables.Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5–24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = −1.92, 95% CI = −3.77 to −0.06, p = 0.042; severe: β = −2.91, 95% CI = −3.97 to −1.86, p < 0.001).Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.

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, R2 = 0.2326), middle (0.0054, R2 = 0.2376), and superior temporal gyri (p = 0.0066, R2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R2 = 0.3685), the inferior (p = 0.0004, R2 = 0.3537), and the middle temporal gyri (p = 0.0001, R2 = 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.

ObjectiveTo describe the clinical, neurological, neuroimaging and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center.MethodsWe retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020.ResultsFifty-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), pConclusionIn 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.

Background: Recent studies indicate that psychiatric and neurocognitive symptoms are frequent after Coronavirus Disease-2019 (COVID-19). The present study aims to investigate the occurrence of psychiatric and cognitive impairments in a cohort of survivors from moderate or severe forms of COVID-19. Methods: 425 adults (mean age 55.7 years) were assessed 6 to 9 months after hospital discharge with a structured psychiatric interview (Clinical Interview Schedule, CIS-R) and a combination of psychometric tests. Cognitive state was examined with a subjective memory complaint scale and screening tests. A large, multidisciplinary, set of clinical data depicting the acute phase of the disease, along with relevant psychosocial variables, were used to predict psychiatric and cognitive outcomes using the ‘Least Absolute Shrinkage and Selection Operator’ (LASSO) method. Outcomes: CIS-R diagnoses of ‘depression’, ‘generalized anxiety disorder’ and ‘post-traumatic stress disorder’ were established respectively in 8%, 15.5% and 13.6% of the sample. Memory decline was reported by 51.1% of the patients. Psychiatric or cognitive outcomes were not predicted by any clinical variables related to the severity of acute-phase disease, nor by disease-related psychosocial stressors. Rather, depression and anxiety were only predicted by current frailty and worse general health status. Interpretation: Using a structured psychiatric interview and an objective assessment of cognitive state, we found high rates of psychiatric and cognitive morbidity in the long-term outcome after moderate or severe COVID-19. The lack of associations of previous medical or psychosocial factors with these diagnoses suggests a direct, disease-related, mechanism in the pathophysiology of COVID-19 related psychiatric and cognitive impairments. Funding: This work was partially supported by donations from the general public under the HC-COMVIDA crowdfunding scheme (https://viralcure.org/c/hc) and the Fundacao Faculdade de Medicina (ALA). ARB receives scholarships and support from FAPESP, the Brazilian National Council of Scientific Development (CNPq-1B), University of Sao Paulo Medical School (FMUSP), the UK Academy of Medical Sciences (Newton Advanced Fellowship), and the International Health Cohort Consortium (IHCC). Conflict of Interest: Authors Declare no Conflict of Interest. Ethical Approval: This research protocol has been approved by the Ethics Committee at HCFMUSP (CAPPesq HC), and registered at the Brazilian Registry of Clinical Trials (ReBEC) under the registration number 4.270.242 (RBR-8z7v5wc) and will be reported according to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement.

Background: Telemedicine was first introduced in Neurology as a tool to facilitate access to acute stroke treatment. More recently, evidence has emerged of the use of telemedicine in several other areas of Neurology. With the advent of the COVID-19 pandemic and the need for social isolation, Brazilian authorities have expanded the regulation of the use of telemedicine, thus allowing the treatment of many patients with neurological diseases to be conducted with less risk of SARS-CoV-2 contamination. Objective: This study aimed to critically review the current evidence of the use, efficacy, safety, and usefulness of telemedicine in Neurology. Methods: A review of PubMed indexed articles was carried out by searching for the terms “telemedicine AND”: “headache”, “multiple sclerosis”, “vestibular disorders”, “cerebrovascular diseases”, “epilepsy”, “neuromuscular diseases”, “dementia”, and “movement disorders”. The more relevant studies in each of these areas were critically analyzed. Results: Several articles were found and analyzed in each of these areas of Neurology. The main described contributions of telemedicine in the diagnosis and treatment of such neurological conditions were presented, indicating a great potential of use of this type of assistance in all these fields. Conclusion: Current evidence supports that teleneurology can be a tool to increase care for patients suffering from neurological diseases.

Background: After the public health emergency due to COVID-19 was declared in Brazil, the federal government temporarily regulated and authorized the use of telemedicine services for patient consultation, monitoring, and diagnosis. For more than a decade, neurologists have recognized the benefits of telemedicine in the acute management of stroke patients. However, as the use of telemedicine was restricted until the COVID-19 pandemic, the view of Brazilian neurologists about telemedicine is unknown. Methods: All neurologists registered at the Brazilian Academy of Neurology were invited by e-mail to participate in a survey about personal perceptions on telemedicine use. Results: One hundred sixty-two neurologists from all regions of Brazil answered the online questionnaire. The survey showed that 18.5% of participants worked with telemedicine before the pandemic, while 63.6% reported working with telemedicine during the pandemic. The main telemedicine modalities used during the pandemic were teleorientation and teleconsultation. Discussion: According to our data, the COVID-19 pandemic deeply influenced the behavior of Brazilian neurologists, who developed a more favorable view about telemedicine and actively searched for information about telemedicine. As there is a need for more training in this area in Brazil, universities and medical societies must strive to improve telemedicine education. Expanding the use of high-quality teleneurology can contribute to a better care for patients with neurological diseases in Brazil.

A 59-year-old right-handed hypertensive diabetic and previously alcoholic man presented acute confusional state followed by apathy, dysexecutive syndrome, clumsy left hand, and apraxic gait. A year later, his wife noticed impaired hearing. Neurologic examination revealed marked callosal apraxia (nondominant limb ideomotor apraxia, disconnection variant) and left stereoagnosis due to callosal disconnection (video). Left hand agraphia was present without aphasia. MRI showed punched out holes through corpus callosum, sparing the calloso-septal interface (figure 1). Audiometry revealed left neurosensorial loss. Fluorescein retinography demonstrated hyperfluorescence of arterial vessel wall (figure 2), confirming the hypothesis of Susac syndrome.1

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.Adaptation of TOP-J for a Brazilian sample, preparation of a reduced version and verification of the accuracy of both.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).On both TOP-J-Br versions, controls outperformed MCI, AD and FTDbv patients (p0.001) and MCI outperformed AD and FTDbv (p0.001). 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.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.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.Adaptação do TOP-J para amostra brasileira, elaboração de uma versão reduzida e verificação da acurácia de ambas.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).Nas duas versões do TOP-J-Br, os controles superaram os CCL, DA e DFTvc (p0,001) e o grupo CCL superou os grupos DA e DFTvc (p0,001). 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.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.

Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

The recent development of IQ-CSF, the second generation of real-time quaking-induced conversion (RT-QuIC) using cerebrospinal fluid (CSF), for the diagnosis of Creutzfeldt-Jakob Disease (CJD) represents a major diagnostic advance in the field. Highly accurate results have been reported with encouraging reproducibility among different centers. However, availability is still insufficient, and only a few research centers have access to the method in developing countries. In Brazil, we have had 603 suspected cases of CJD since 2005, when surveillance started. Of these, 404 were undiagnosed. This lack of diagnosis is due, among other factors, to the lack of a reference center for the diagnosis of these diseases in Brazil, resulting in some of these samples being sent abroad for analysis. The aim of this research study is to report the pilot use of IQ-CSF in a small cohort of Brazilian patients with possible or probable CJD, implementing a reference center in the country. We stored CSF samples from patients with possible, probable or genetic CJD (one case) during the time frame of December 2016 through June 2018. All CSF samples were processed according to standardized protocols without access to the clinical data. Eight patients presented to our team with rapidly progressive dementia and typical neurological signs of CJD. We used CSF samples from seven patients with other neurological conditions as negative controls. Five out of seven suspected cases had positive tests; two cases showed inconclusive results. Among controls, there was one false-positive (a CSF sample from a 5-year-old child with leukemia under treatment). The occurrence of a false positive in one of the negative control samples raises the possibility of the presence of interfering components in the CSF sample from patients with non-neurodegenerative pathologies. Our pilot results illustrate the feasibility of having CJD CSF samples tested in Brazilian centers and highlight the importance of interinstitutional collaboration to pursue a higher diagnostic accuracy in CJD in Brazil and Latin America.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of β-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess β-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aβ deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aβ deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

Background Short-term memory binding (STMB) tests assess conjunctive binding, in which participants should remember the integration of features, such as shapes (or objects) and colors, forming a unique representation in memory. In this study, we investigated two STMB paradigms: change detection (CD) and free recall (FR). Objective To investigate the cognitive profile in the CD and FR tasks of three diagnostic groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's clinical syndrome (ACS). In addition, we aimed to calculate and compare the accuracy of the CD and FR tasks to identify MCI and ACS. Methods Participants were 24 CU, 24 MCI, and 37 ACS. The cognitive scores of the clinical groups were compared using analysis of variance (ANOVA) and receiver-operating characteristic (ROC) analyses were carried out to verify the accuracy of the STMB tasks. Results In the CD task, CU was different from MCI and ACS (CU > MCI = ACS), while in the FR task all groups were different (CU > MCI > ACS). The ROC analyses showed an area under the curve (AUC) of 0.855 comparing CU with MCI for the CD task and 0.975 for the FR. The AUC comparing CU and ACS was 0.924 for the CD and 0.973 for the FR task. The FR task showed better accuracy to identify MCI patients, and the same accuracy to detect ACS. Conclusion The present findings indicate that impairments in CD and FR of bound representations are features of the cognitive profiles of MCI and ACS patients.

Cerebral autoregulation (AR) keeps cerebral blood flow constant despite fluctuations in systemic arterial pressure. The final common AR pathway is made up of vasomotor adjustments of cerebrovascular resistance mediated by arterioles. Structural and functional changes in the arteriolar wall arise with age and systemic arterial hypertension. This study evaluated whether AR is impaired in hypertensive patients and whether this impairment differs with disease control. Three groups of patients were prospectively compared: hypertensive patients under treatment with systolic blood pressure (SBP) 140 or DBP > 90 mm Hg (n = 31), and normotensive volunteers (n = 30). Simultaneous measurements of cerebral blood flow velocity (CBFV) and BP were obtained by digital plethysmography and transcranial Doppler, and the AR index (ARI) was defined according to the step response to spontaneous fluctuations in BP. Compared to the uncontrolled hypertension, the normotensive individuals were younger (age 43.42 ± 11.14, P

Background: Central nervous system changes associated to systemic arterial hypertension (SAH) are progressive and may cause negative effects on cognitive performance. The objective of this study was to investigate the relation between SAH and the components of executive functions (EF), inhibitory control (IC), updating and shifting, comparing a control group (without SAH) to patients with SAH, in two levels of severity. Methods: The protocol included the following tests to evaluate EF components: T.O.V.A. Test (IC), Backward Digit Span from Wechsler Adults Intelligence Scale (WAIS-III), Phonemic and Semantic Verbal Fluency (updating), and Trail Making Test Part B (shifting). Results: A total of 204 participants was included: 56 from the Control Group (CG), 87 SAH stage 1, and 61 SAH stage 2. The groups were not different for age (52.37±12.29) and education (10.98±4.06). As to controlled blood pressure (BP), duration of hypertension treatment and number of drugs, the SAH 2 group had a worse BP control, longer duration of hypertension treatment and use of more drugs when compared to the SAH 1. The findings revealed that patients with more severe hypertension presented worse performance in updating (Backward Digit Span, phonemic and semantics VF) and shifting (Trail Making Test Part B). Conclusion: The results suggest that patients with SAH have a significant impairment in EF, more specifically in updating and shifting. Besides that, such damage may be directly proportional to the severity of SAH. It is suggested that future studies include neuroimaging exams to exclude possible cerebrovascular diseases. RESUMO Introdução: As alterações do sistema nervoso central associadas à hipertensão arterial sistêmica (HAS) são progressivas e podem ocasionar efeitos negativos no desempenho cognitivo. O objetivo deste estudo foi investigar a relação entre a HAS e os componentes das funções executivas (FE), controle inibitório (CI), atualização e alternância, comparando um grupo controle (sem HAS) a pacientes com HAS, em dois níveis de gravidade. Métodos: O protocolo incluiu os seguintes testes para avaliar os componentes das FE: T.O.V.A. Test (CI), Dígitos Ordem Indireta da Escala de Inteligência Wechsler para Adultos (Wechsler Adults Intelligence Scale - WAIS-III), Fluência Verbal fonêmica e semântica (atualização) e Teste de Trilhas parte B (alternância). Resultados: Foram incluídos 204 participantes, sendo 56 do Grupo Controle (GC), 87 HAS estágio 1 (HAS 1) e 61 de HAS estágio 2 (HAS 2). Os grupos não foram diferentes em relação à idade (52,37±12,29) e escolaridade (10,98±4,06). Em relação à pressão arterial (PA) controlada, tempo de tratamento da HAS e número de medicações, o grupo HAS 2 apresentou pior controle de PA, mais tempo de tratamento da HAS e uso de maior número de medicações quando comparado ao grupo HAS 1. Os achados revelaram que os pacientes com HAS em estágio mais grave apresentaram pior desempenho nos testes de alternância (Teste de Trilhas parte B) e atualização (Dígitos Ordem Indireta, FV fonêmica e semântica). Conclusão: Esses resultados sugerem que pacientes com a HAS possuem prejuízo significativo em FE, especificamente em alternância e atualização, e que esse prejuízo pode ser diretamente proporcional à gravidade da HAS. Sugere-se que, em estudos futuros, incluam-se exames de neuroimagem com o objetivo de excluir possíveis doenças cerebrovasculares.

Introduction: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). Objectives: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale−frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). Methods: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. Results: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. Conclusions: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum.

OBJECTIVES The objectives of this study were to evaluate the effects of the Tailored Activity Program-Brazilian version (TAP-BR), on behavioral symptoms and the quality of life (QOL) in persons with dementia, as well as on their caregivers, and on caregiver burden. MATERIALS AND METHODS A 2-group randomized controlled trial with 30 dyads was conducted: the experimental group (n=15) received TAP-BR over 4 months, and a wait-list control group (n=15) received usual care. Dyads were recruited from the community of Santos City, Brazil. RESULTS For persons with dementia, 50% were female individuals, the average age was 81.37 (±7.57), and the educational level was 9.97 (±5.32) years. For caregivers, 83.33% were female, the average age was 65.97 (±10.13), and the educational level was 12.10 (±4.44) years. At posttest, in comparison with the wait-list control group, experimental group caregivers reported greater reductions in number (P

Introduction Executive dysfunction is a common symptom in neurodegenerative disorders and is in need of easy-to-apply screening tools that might identify it. The aims of the present study were to examine some of the psychometric characteristics of the Brazilian version of the INECO frontal screening (IFS), and to investigate its accuracy to diagnose executive dysfunction in dementia and its accuracy to differentiate Alzheimer disease (AD) from the behavioral variant of frontotemporal dementia (bvFTD). Methods Patients diagnosed with bvFTD (n=18) and AD (n=20), and 15 healthy controls completed a neuropsychological battery, the Neuropsychiatric Inventory, the Cornell Scale for Depression in Dementia, the Clinical Dementia Rating, and the IFS. Results The IFS had acceptable internal consistency (α=0.714) and was significantly correlated with general cognitive measures and with neuropsychological tests. The IFS had adequate accuracy to differentiate patients with dementia from healthy controls (AUC=0.768, cutoff=19.75, sensitivity=0.80, specificity=0.63), but low accuracy to differentiate bvFTD from AD (AUC=0.594, cutoff=16.75, sensitivity=0.667, specificity=0.600). Conclusion The present study suggested that the IFS may be used to screen for executive dysfunction in dementia. Nonetheless, it should be used with caution in the differential diagnosis between AD and bvFTD.

The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD. RESUMO A associação entre Doença de Alzheimer (DA) e distúrbios do sono vem recebendo atenção crescente nas últimas décadas. No entanto, pouco se sabe sobre o impacto do sono e suas alterações no desenvolvimento de estágios pré-clínicos da doença, como é o caso do Comprometimento Cognitivo Leve (CCL). Esta revisão descreve a evolução do conhecimento sobre as relações potencialmente bidirecionais entre DA e distúrbios do sono, explorando grandes estudos prospectivos e meta-análises, assim como estudos dos possíveis mecanismos da associação entre o sono e as doenças neurodegenerativas. Também revisamos amplamente as características do sono de pessoas idosas, incluindo indivíduos cognitivamente normais, com CCL e com demência por DA.

The Montreal Cognitive Assessment (MoCA) has been described as a good tool to detect cognitive impairment. The ideal MoCA cutoff score is still under debate. The aim was to provide MoCA norms and accuracy data for seniors with a lower education level, including illiterates. Methods: Data originated from an epidemiological study conducted in the municipality of Tremembe, Brazil. The Brazilian MoCA test was applied as part of the cognitive assessment in all participants. Of the 630 participants, 385 were classified as cognitively normal (CN) and were included in the normative data set, 110 individuals were diagnosed with dementia and 135 were classified as having cognitive impairment no dementia (CIND). Results: The total scores varied significantly according to age and education among the three diagnostic groups: CN, CIND and dementia (p < 0.001). To distinguish participants with CN from dementia, the best MoCA cutoff was 15 points (sensitivity 90%, specificity 77%) and to differentiate those with CN from CIND, the MoCA cutoff was 19 points (sensitivity 84%, specificity 49%). Those scores varied according to education level. Conclusions: The MoCA test did not have a high accuracy for detecting CIND in the population with a low educational level. Nevertheless, this tool may be used to detect dementia, especially in individuals with more than five years of education, if a lower cutoff score is adopted. RESUMO O Montreal Cognitive Assessment (MoCA) foi descrito como uma boa ferramenta para detectar comprometimento cognitivo. A nota de corte ideal do MoCA ainda está em debate. O objetivo é fornecer normas do MoCA e dados de acurácia para idosos dentro de uma faixa educacional mais baixa, incluindo analfabetos. Métodos: Os dados foram provenientes do estudo epidemiológico realizado no município de Tremembé, Brasil. A versão brasileira do MoCA foi aplicada como parte da avaliação cognitiva em todos os participantes. Dos 630 participantes, 385 foram classificados como cognitivamente normais (CN) e foram incluídos no conjunto de dados normativos, 110 indivíduos foram diagnosticados com demência e 135 foram classificados como tendo comprometimento cognitivo sem demência (CCSD). Resultados: Os escores totais variaram significativamente de acordo com a idade e escolaridade entre os três grupos diagnósticos: CN, CCSD e demência (p < 0,001). Para distinguir CN de demência, a melhor nota de corte do MoCA foi de 15 pontos (sensibilidade 90%, especificidade 77%) e para diferenciar o grupo CN de CCSD, a nota de corte do MoCA foi de 19 pontos (sensibilidade 84%, especificidade 49%). Essas notas de corte variaram conforme o nível de escolaridade. Conclusões: O teste MoCA não teve alta acurácia para detectar CCSD nesta população de baixa escolaridade. No entanto, esta ferramenta poderia ser usada para detectar demência, especialmente em indivíduos com mais de 5 anos de escolaridade, se uma menor nota de corte fosse adotada.