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Mild cognitive impairment (MCI) refers to cognitive alterations with preservation of functionality. Individuals with this diagnosis have a higher risk of developing dementia. Non-pharmacological interventions, such as physical exercise, are beneficial for the cognition of this population. However, the impact of resistance training (RT) on the brain anatomy of older adults with MCI has not yet been clarified. This study aimed to investigate the effects of RT on cognition and brain anatomy in MCI. Forty-four older adults with MCI, 22 in the training group and 22 in the control group, were evaluated in neuropsychological tests and magnetic resonance imaging at the beginning and end of the study, which lasted 24 weeks. We used repeated measures ANOVA. The training group showed better performance in verbal episodic memory after intervention. The control group showed a decrease in gray matter volume in the hippocampus and precuneus, while the training group showed no reduction in the right hippocampus and precuneus. However, it showed a decrease in the volume of these regions on the left side and in the left superior frontal gyrus. In the analysis of white matter integrity, fractional anisotropy increased in the training group and decreased in the control group. Axial diffusivity decreased in the training group, while radial diffusivity increased in the control group, and mean diffusivity varied according to the tract evaluated. RT improves memory performance, positively influences white matter integrity parameters, and plays a protective role against atrophy of the hippocampus and precuneus in MCI., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Novel therapies for Alzheimer's disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment. Future work involves further research on anti-amyloid therapies in Brazil and the development of more effective treatments for Alzheimer's disease., Competing Interests: Disclosure: The authors report no conflicts of interest.

In recent years, the diagnostic accuracy of Alzheimer's disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there is concern about the indiscriminate and poorly supported use of biomarkers, especially in asymptomatic individuals or those with subjective cognitive decline. Difficulties interpreting these tests, high costs, and unequal access make this scenario even more challenging in healthcare. This article presents the recommendations from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology ( Departamento Científico de Neurologia Cognitiva e Envelhecimento da Academia Brasileira de Neurologia ) regarding the rational use and interpretation of Alzheimer's disease biomarkers in clinical practice. The clinical diagnosis of cognitive-behavioral syndrome is recommended as the initial step to guide the request for biomarkers., Competing Interests: Disclosure: The authors report no conflicts of interest.

Several studies have aimed at identifying biomarkers in the initial phases of Alzheimer's disease (AD). Conversely, texture features, such as those from gray-level co-occurrence matrices (GLCMs), have highlighted important information from several types of medical images. More recently, texture-based brain networks have been shown to provide useful information in characterizing healthy individuals. However, no studies have yet explored the use of this type of network in the context of AD. This work aimed to employ texture brain networks to investigate the distinction between groups of patients with amnestic mild cognitive impairment (aMCI) and mild dementia due to AD, and a group of healthy subjects. Magnetic resonance (MR) images from the three groups acquired at two instances were used. Images were segmented and GLCM texture parameters were calculated for each region. Structural brain networks were generated using regions as nodes and the similarity among texture parameters as links, and graph theory was used to compute five network measures. An ANCOVA was performed for each network measure to assess statistical differences between groups. The thalamus showed significant differences between aMCI and AD patients for four network measures for the right hemisphere and one network measure for the left hemisphere. There were also significant differences between controls and AD patients for the left hippocampus, right superior parietal lobule, and right thalamus-one network measure each. These findings represent changes in the texture of these regions which can be associated with the cortical volume and thickness atrophies reported in the literature for AD. The texture networks showed potential to differentiate between aMCI and AD patients, as well as between controls and AD patients, offering a new tool to help understand these conditions and eventually aid early intervention and personalized treatment, thereby improving patient outcomes and advancing AD research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Little is known about changes in the brain associated with frailty, in particular, which brain areas could be related to frailty in older people without cognitive impairment. This scoping review mapped evidence on functional and/or structural brain changes in frail older adults without cognitive impairment. The methodology proposed by the JBI® was used in this study. The search in PubMed, PubMed PMC, BVS/BIREME, EBSCOHOST, Scopus, Web of Science, Embase, and PROQUEST was conducted up to January 2023. Studies included following the population, concepts, context and the screening and data extraction were performed by two independent reviewers. A total of 9,912 records were identified, 5,676 were duplicates and were excluded. The remaining articles were screened; 31 were read in full and 17 articles were included. The results showed that lesions in white matter hyperintensities, reduced volume of the hippocampus, cerebellum, middle frontal gyrus, low gray matter volume, cortical atrophy, decreased connectivity of the supplementary motor area, presence of amyloid-beta peptide (aβ) in the anterior and posterior putamen and precuneus regions were more frequently observed in frail older adults, compared with non-frail individuals. Studies have suggested that such findings may be of neurodegenerative or cerebrovascular origin. The identification of these brain alterations in frail older adults through neuroimaging studies contributes to our understanding of the underlying mechanisms of frailty. Such findings may have implications for the early detection of frailty and implementation of intervention strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care., Objective: The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil., Methods: We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology ( n  = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 ( n  = 187). The invitation was also diffused through social media., Results: 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) ( n  = 211), bipolar disorder ( n  = 117) and dementia with Lewy bodies ( n  = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively., Conclusions: The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: The response to cholinesterase inhibitors (ChEIs) treatment is variable in patients with Alzheimer's disease (AD). Patients and physicians would benefit if these drugs could be targeted at those most likely to respond in a clinical setting. Therefore, this study aimed to evaluate the ability of cerebrospinal fluid (CSF) AD biomarkers, hippocampal volumes, and Default Mode Network functional connectivity to predict clinical response to ChEIs treatment in mild AD. Methods: We followed up on 39 mild AD patients using ChEIs at therapeutic doses. All subjects underwent clinical evaluation, neuropsychological assessment, magnetic resonance imaging examination, and CSF biomarkers quantification at the first assessment. The Mini-Mental Status Examination (MMSE) was used to measure the global cognitive status before and after the follow-up. "Responders" were considered as those who have remained stable or improved the MMSE score between evaluations and "Nonresponders" as those who have worsened the MMSE score. We performed univariate and multivariate logistic regressions to predict the clinical response from each biomarker. Results: About 35.89% of patients were classified as "Responders" to ChEIs treatment after the follow-up. The multivariate model with measures of Right Hippocampus (RHIPPO), adjusted for gender and interval between assessments, was significant (odds ratio: 1.09 [95% confidence interval, 1.00-1.19], p  = 0.0392). This model achieved an accuracy of 77.60%. Conclusion: Our findings suggest that the functional connectivity of RHIPPO might be an early imaging biomarker to predict clinical response to ChEIs drugs in mild AD. Impact statement The functional connectivity of the right hippocampus showed a direct relationship with the clinical response to cholinesterase inhibitors (ChEIs) treatment in patients with mild Alzheimer's disease. Transposing our findings to clinical settings could allow physicians to prescribe ChEIs for patients for whom treatment would be most beneficial.

The causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (Aβ 42 ) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole-brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with Aβ 42 alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of Aβ 42 , phosphorylated tau protein (p-Tau) and total tau (t-Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p-Tau and t-Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early-stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pela Biogen; RN: Participação no conselho consultivo da Biogen; JBP, VT, HBF, MS, MTB, BJAPB, FACV, MLFG, SMDB, RMC, NAFF: Não há conflito de interesse a declarar.

Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen and Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; RN: Participação no conselho consultivo do laboratório Biogen; BJAPB, JISN, GSA, FKS, CKS, FTM, NAFF, FACV, SMDB, EE, MLFC: There is no conflict of interest to declare.

"Frontotemporal dementia" (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging., Competing Interests: Conflito de interesses: : LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participation in advisory boards for Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participation in advisory boards for Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação nos conselhos consultivos dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação nos conselhos consultivos dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; RN: Participação no conselho consultivo do laboratório Biogen; MLH, THM, MTCG, MSY, BJAPB, NAFF, FACV, MLFC, SMDB, VSB, LTT: There is no conflict of interest to declare.

There is currently no cure for neurodegenerative or vascular dementias, but some pharmacological and non-pharmacological interventions may contribute to alleviate symptoms, slow disease progression and improve quality of life. Current treatment approaches are based on etiology, symptom profile and stage of dementia. This manuscript presents recommendations on pharmacological and non-pharmacological treatments of dementia due to Alzheimer's disease, vascular cognitive impairment, frontotemporal dementia, Parkinson's disease dementia, and dementia with Lewy bodies., Competing Interests: Conflito de interesses: : PC: Participação como investigador principal em ensaios clínicos patrocinados pelos laboratórios Novo Nordisk e Roche. Atividades de consultoria para os laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; VM: Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios Biogen, Sandoz e Torrent; JS: Participação como palestrante em simpósios patrocinado pelo laboratório Roche; LPS: Atividades de consultoria para o laboratório Biogen. Participação como palestrante em simpósios patrocinados pelos laboratórios Aché, Apsen e Biogen; MLFB: Atividades de consultoria para o laboratório Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios patrocinados pelos laboratórios EMS e Torrent; PHFB: Atividades de consultoria para os laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk, e para a Quintiles. Participação como palestrante em simpósios patrocinados pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Atividades de consultoria para o laboratório Biogen. Participação como palestrante em simpósios patrocinados pela Biogen; RN: Participação no conselho consultivo do laboratório; JL, MVDC, FS, EFC, BJAPB, NAFF, FACV, MLFC, SMDB, HBD: Não há conflito de interesse a declarar.

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., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação em conselhos consultivos da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação em conselhos consultivos da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação em conselhos consultivos para os laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação em conselhos consultivos para os laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; EPFR: Alzheimer’s Association, World Federation of Neurology and National Institute of Health (concessão número R21AG069252); LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; RN: Participação no conselho consultivo do laboratório Biogen; KGCF, MCND, RK, ASN, BJAPB, NAFF, MLFC, SMDB, FACV: Não há conflito de interesse a declarar.

Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo do laboratório Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação nos conselhos consultivos dos laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pela Biogen; RN: Participação no conselho consultivo do laboratório Biogen; SMDB, IP, WVB, VC, CELF, BJAPB, NAFF, FACV, MLFC, RRS, LSM: Não há conflito de interesse a declarar.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research., Competing Interests: Conflito de interesses: : LPS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo do laboratório Biogen. Desenvolvimento de material para educação continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; JS: Participação como palestrante em simpósio promovido pelo laboratório Roche; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodia; PHFB: Participação em advisory boards dos laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovido pelos laboratórios Apsen, Nutricia, RN: Participação no conselho consultivo do laboratório Biogen; Roche e Sandoz; LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen. MR, OVF, MLS, BJAPB, NAFF, FACV, MLFC, SMDB, BPD, : declaram não haver conflito de interesse.

Introduction: Synaptophysin, already related to X-linked intellectual disability, is expressed mainly in the central nervous system. Studies in humans indicate that the downregulation of synaptophysin could be involved in the development of dementia. Our study presents the first familial case of behavioral variant frontotemporal dementia associated with the co-occurrence of the repeat expansion in C9orf72 and a pathogenic variant in the SYP gene., Methods: Exome sequencing and repeat-primed PCR for C9orf72 were performed for two siblings with clinical and imaging findings suggestive of slowly progressive behavioral frontotemporal dementia., Results: We found that both siblings have the hexanucleotide expansion in C9orf72 and a null variant in the SYP gene. The most affected sibling presents the putative variant in a hemizygous state. With milder symptoms, his sister has the same pathogenic variant in heterozygosis, compatible with X-linked inheritance., Discussion: Our results strengthened previous suggestive evidence that the phenotypes associated with C9orf72 repeat expansion are variable and probably influenced by additional genetic modifiers. We hypothesized that the pathogenic variant in the SYP gene might have modified the typical phenotype associated with the C9orf72 mutation., (© 2021 the Alzheimer's Association.)

Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways., Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders., Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome., Results: targeted taxa were described and grouped from major studies to each disease., Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

Purpose: Default mode network (DMN) has emerged as a potential biomarker of Alzheimer's disease (AD); however, it is not clear whether it can differentiate amnestic mild cognitive impairment with altered amyloid (aMCI-Aβ +) who will evolve to AD. We evaluated if structural and functional connectivity (FC), hippocampal volumes (HV), and cerebrospinal fluid biomarkers (CSF-Aβ 42 , p-Tau, and t-Tau) can differentiate aMCI-Aβ + converters from non-converters., Methods: Forty-eight individuals (18 normal controls and 30 aMCI subjects in the AD continuum - with altered Aβ 42 in the CSF) were followed up for an average of 13 months. We used MultiAtlas, UF 2 C, and Freesurfer software to evaluate diffusion tensor imaging, FC, and HV, respectively, INNOTEST® kits to measure CSF proteins, and neuropsychological tests. Besides, we performed different MANOVAs with further univariate analyses to differentiate groups., Results: During follow-up, 8/30 aMCI-Aβ + converted (26.6%) to AD dementia. There were no differences in multivariate analysis between groups in CSF biomarkers (p = 0.092) or at DMN functional connectivity (p = 0.814). aMCI-Aβ + converters had smaller right HV than controls (p = 0.013), and greater right cingulum parahippocampal bundle radial diffusivity than controls (p < 0.001) and non-converters (p = 0.036)., Conclusion: In this exploratory study, structural, but not functional, DMN connectivity alterations may differentiate aMCI-Aβ + subjects who converted to AD dementia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based concept that underlying etiology has not been completely understood. Refers to a group of individuals that are negative for amyloid biomarkers and positive for p-Tau and/or neurodegeneration. SNAP causes great research interest because it is not clear if they have a different biological basis from Alzheimer's disease (AD), or are in an early stage of AD itself. The pathological processes behind SNAP need to be clarified. This mini-review aims to summarize the main characteristics of SNAP, besides reporting challenges and promising biomarkers related to the concept., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical managements. Objective: To test whether the Neuropsychiatry Inventory (NPI) could detect change in neuropsychiatric symptoms and caregiver's distress in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) from baseline to a 12-month follow-up and to investigate possible predictors of change in NPI scores. Methods: The sample consisted of 31 patients diagnosed with bvFTD and 28 patients with AD and their caregivers. The Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), the INECO Frontal Screening (IFS), the Frontal Assessment Battery (FAB), the Executive Interview (EXIT-25) and the NPI were applied. Descriptive statistics, Mann-Whitney U test, Wilcoxon test, Chi square (χ 2 ) test and Linear Regression Analysis were used. Results: NPI total and caregiver distress scores were statistically higher among bvFTD patients at both assessment points. MMSE, ACE-R scores significantly declined and NPI Total and Distress scores significantly increased in both groups. In the bvFTD group, age was the only independent predictor variable for the NPI total score at follow up. In the AD group, ACE-R and EXIT-25, conjunctively, were associated with the NPI total score at follow up. Conclusions: In 12 months, cognition declined and neuropsychiatric symptoms increased in bvFTD and AD groups. In the AD group only, cognitive impairment was a significant predictor of change in neuropsychiatric symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Da Silva, Ordonez, Bregola, Bahia, Cecchini, Guimarães, Gambogi, Caramelli, Balthazar, Damasceno, Brucki, de Souza, Nitrini and Yassuda.)

Objectives: Atrial fibrillation (AF) is associated with high risk of dementia and brain atrophy in stroke-free patients, but the mechanisms underlying this association remain unclear. We aimed to examine the brain volume and connectivity of paramount cognitive brain networks in stroke-free patients with AF without dementia., Materials and Methods: Twenty-six stroke-free patients with AF and 26 age and sex-matched subjects without AF were submitted to a 3-tesla brain structural and functional MRI. An extensive clinical evaluation excluded stroke, dementia, low cardiac output, carotid stenosis and metabolic diseases without optimal therapy. We used CHA 2 DS 2 -VASc score to classify the cardiovascular risk factor burden and a broad neuropsychological battery to assess the cognitive performance. Voxel based morphometry analysis of. structural MRI defined whole-brain gray and white matter volumes. Finally, we used eco-plannar MRI images to compare the differences of functional connectivity of 7 large-scale resting-state networks between AF patients and controls., Results: Taking into account the history of hypertension and heart failure, AF was associated to volume decrease of the right basal frontal lobe and right inferior cerebellum. Decreased connectivity of the ventral Default Mode Network (vDMN) was observed in the AF group. No disruption of connectivity was observed in the executive, visuospatial and salience networks., Conclusion: Individuals with AF without stroke or dementia have subtle reduction of gray and white matter, restricted to frontal areas and cerebellum. These patients show decreased vDMN connectivity, without other large-scale brain network disruption., Competing Interests: Declaration of Competing Interest All the authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The last years have evinced a remarkable growth in neuroimaging studies around the world. All these studies have contributed to a better understanding of the cerebral outcomes of dementia, even in the earliest phases. In low- and middle-income countries, studies involving structural and functional neuroimaging are challenging due to low investments and heterogeneous populations. Outstanding the importance of diagnosing mild cognitive impairment and dementia, the purpose of this paper is to offer an overview of neuroimaging dementia research in Brazil. The review includes a brief scientometric analysis of quantitative information about the development of this field over the past 10 years. Besides, discusses some peculiarities and challenges that have limited neuroimaging dementia research in this big and heterogeneous country of Latin America. We systematically reviewed existing neuroimaging literature with Brazilian authors that presented outcomes related to a dementia syndrome, published from 2010 to 2020. Briefly, the main neuroimaging methods used were morphometrics, followed by fMRI, and DTI. The major diseases analyzed were Alzheimer's disease, mild cognitive impairment, and vascular dementia, respectively. Moreover, research activity in Brazil has been restricted almost entirely to a few centers in the Southeast region, and funding could be the main driver for publications. There was relative stability concerning the number of publications per year, the citation impact has historically been below the world average, and the author's gender inequalities are not relevant in this specific field. Neuroimaging research in Brazil is far from being developed and widespread across the country. Fortunately, increasingly collaborations with foreign partnerships contribute to the impact of Brazil's domestic research. Although the challenges, neuroimaging researches performed in the native population regarding regional peculiarities and adversities are of pivotal importance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rizzi, Aventurato and Balthazar.)

Alzheimer's disease (AD) is a neurodegenerative condition that affects a large number of elderly people worldwide and has a high social and economic impact. The diagnosis of AD in early stage can significantly improve the evolution and prognosis of the disease. We report the use of A Disintegrin And Metalloprotease 10 (ADAM10) as a blood biomarker for the early diagnosis of AD. A simple, low-cost, sensitive, and disposable microfluidic platform (DμP) was developed for ADAM10 detection in plasma and cerebrospinal fluid based on electrochemical immunosensors. The assay was designed to accurately detect ADAM10 in serum, with a limit of detection of 0.35 fg/mL. ADAM10 was detected in subjects divided into cognitively healthy subjects, subjects with mild cognitive impairment, and AD patients in different disease stages. An increase in protein levels was found throughout the disease, and good DμP accuracy in differentiating individuals was observed. The DμP provided significantly better sensitivity than the well-established enzyme-linked immunosorbent assay test. ADAM10 and its detection using the DμP were proven to be an alternative tool for the early diagnosis and monitoring of AD, bringing new exciting possibilities to improve the quality of life of AD patients.

Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-α) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive decline and behavioral changes are common features in amyotrophic lateral sclerosis (ALS) and imply worse prognosis as well as increased disease burden for patients and caregivers. Currently, there is a lack of studies regarding behavioral profile in Brazilian ALS cohorts. We assessed the prevalence and profile of behavioral impairment ( ALSbi ) in a Brazilian non-demented C9orf72-negative ALS cohort according to broad behavioral assessment and the latest consensus. Among 76 initially recruited consecutive ALS patients, 70 were included, including seven ALS type 8 ( VAPB -related ALS) individuals. Patients with Frontotemporal Dementia (FTD) diagnosis were excluded. Sixteen ALS patients (23%) were diagnosed as ALSbi . Among ALS type 8 individuals, 2 (28.6%) were diagnosed as ALSbi . Neuropsychiatric Inventory Questionnaire (NPI) total scores did positively correlate with age, but not with other demographic or clinical data. Apathy was the most prevalent finding in the ALSbi subgroup, although the prevalence (20%) was smaller than reported in previous literature. Dysphoria and anxiety were also prevalent findings in the whole ALS cohort. Future studies with larger cohorts and validated ALS-specific tools are needed in order to expand our knowledge.

Objective: It is still unclear how temporal lobe epilepsy (TLE) with and without hippocampal atrophy (HA) affects cortical language distribution. We aimed to investigate the role of the hippocampus on language lateralization, activation pattern, and functional connectivity (FC) in patients with TLE., Methods: We investigated 93 patients with TLE-divided into right HA (RHA), left HA (LHA), and negative magnetic resonance imaging (MRI) (non-HA)-and 101 controls using a semantic-language functional MRI (fMRI) task and the Boston Naming Test (BNT)., Results: Groups did not differ in the frequency of atypical language lateralization (LL), which correlated differently with handedness in each brain region and group. Blood-oxygen-level dependend (BOLD) activation patterns and region of interest (ROI)-to-ROI FC differed between LHA and controls, as well as between LHA and non-HA patients. In the task activation pattern analysis, there was a decrease in the activation of patients with LHA relative to controls, exactly in the left hippocampus. However, non-HA patients had increased FC relative to controls in the left superior temporal gyrus region. Seed-to-voxel FC demonstrated greater differences between patients and controls and smaller differences among patient groups. The non-HA group was similar to controls, except for increased BOLD activation and increase FC in the superior temporal gyri. RHA and LHA differed from controls in BNT. BNT correlated with fMRI activation in RHA and non-HA groups., Significance: LHA affected naming performance, fMRI semantic task activation pattern, and FC more than RHA and non-HA. Contrary to our expectations, LHA did not increase the frequency of atypical LL. Regardless of the side, HA impacts negatively on the language network but not on hemispheric language lateralization., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

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.

Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aβ) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1β, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aβ 1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1β than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1β, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aβ 1-42 , and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.

Background: Behavioral variant frontotemporal dementia (bvFTD) has profound consequences on patients and their families. In this multicenter study, we investigated the contribution of cognitive and neuropsychiatric factors to everyday function at different levels of overall functional impairment., Methods: In a retrospective cross-sectional study, 109 patients with bvFTD from 4 specialist frontotemporal dementia centers (Australia, England, India, and Brazil) were included. The measures administered evaluated everyday function (Disability Assessment for Dementia [DAD]), dementia staging (Clinical Dementia Rating [CDR]), general cognition (Addenbrooke's Cognitive Examination-revised [ACE-R]), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). Patients were then subdivided according to functional impairment on the DAD into mild, moderate, severe, and very severe subgroups. Three separate multiple linear regression analyses were run, where (1) total DAD, (2) basic activities of daily living (BADL), and (3) instrumental activities of daily living (IADL) scores were dependent variables; ACE-R total score and selected NPI domains (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) were used as independent variables. Age, sex, education, and country of origin were controlled for in the analyses., Results: Cognitive deficits were similar across the mild, moderate, and severe subgroups but significantly worse in the very severe subgroup. NPI domain scores (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) did not differ across the DAD subgroups. In the multiple regression analyses, a model including ACE-R and NPI apathy explained 32.5% of the variance for total DAD scores. For IADL, 35.6% of the variance was explained by the ACE-R only. No model emerged for BADL scores., Conclusions: Cognitive deficits and apathy are key contributors to functional disability in bvFTD but factors underlying impairment in BADLs remain unclear. Treatments targeting reduction of disability need to address apathy and cognitive impairment to ensure greater efficacy, especially in regards to IADLs.

Background: Atrial fibrillation (AF) is a widely accepted risk for causing stroke. However, recent studies show AF as a risk factor for dementia, even without causing stroke. The mechanisms by which dementia develops in stroke-free patients with AF are still poorly understood and the association of AF with abnormal function of brain networks activities, such as the default mode network (DMN), has not been previously studied. We aimed to determine whether, in the absence of stroke and dementia, patients with AF have abnormal resting-state brain networks compared to controls without AF., Methods: Twenty-one stroke-free patients with AF and 21 age- and sex-matched controls without AF underwent brain functional magnetic resonance imaging acquired at a 3.0 Tesla scanner. During the exam, the subjects were instructed to lie still with eyes closed. At first-level analysis, connectivity of the DMN was obtained for all subjects. Second-level analysis compared the DMN connectivity between AF patients and controls with a general linear model (two-sample t test, p < 0.05, False Discovery Rate corrected, minimum of 50 contiguous voxels)., Results: Patients with AF compared with controls showed decreased connectivity in regions of the DMN including the frontal lobe (left medial frontal gyrus, left superior frontal gyrus and anterior cingulate), left angular gyrus, and bilateral precuneus., Conclusions: Stroke-free patients with AF have evidence of abnormal DMN connectivity. This study adds evidence to the occurrence of cerebral dysfunction in patients with AF., (© 2018 S. Karger AG, Basel.)

Background: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF)., Methods: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease., Results: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas., Limitations: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used., Conclusion: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Different aspects of the self have been reported to be affected in many neurological or psychiatric diseases such as Alzheimer's disease (AD), including mainly higher-level cognitive self-unawareness. This higher sense of self-awareness is most likely related to and dependent on episodic memory, due to the proper integration of ourselves in time, with a permanent conservation of ourselves (i.e., sense of continuity across time). Reviewing studies in this field, our objective is thus to raise possible explanations, especially with the help of neuroimaging studies, for where such self-awareness deficits originate in AD patients. We describe not only episodic (and autobiographical memory) impairment in patients, but also the important role of cortical midline structures, the Default Mode Network, and the resting state (intrinsic brain activity) for the processing of self-related information., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Language tasks used for clinical fMRI studies may be too complex for some patients with cognitive impairments, and "easier" versions are sometimes substituted, though the effects on brain activity of such changes in task complexity are largely unknown. To investigate these differences, we compared two versions of an fMRI language comprehension protocol, with different levels of difficulty, in 24 healthy right-handed adults. The protocol contrasted an auditory word comprehension task (semantic decision) with a nonspeech control task using tone sequences (tone decision). In the "complex" version (CV), the semantic decision task required two complex semantic decisions for each word, and the tone decision task required the participant to count the number of target tones in each sequence. In the "easy" version (EV), the semantic task required only a single easier decision, and the tone task required only detection of the presence or absence of a target tone in each sequence. The protocols were adapted for a Brazilian population. Typical left hemisphere language lateralization was observed in 92% of participants for both CV and EV using the whole-brain lateralization index, and typical language lateralization was also observed for others regions of interest. Task performance was superior on the EV compared to the CV (p=0.014). There were many common areas of activation across the two version; however, the CV produced greater activation in the left superior and middle frontal giri, angular gyrus, and left posterior cingulate gyrus compared to the EV, the majority of which are areas previously identified with language and semantic processing. The EV produced stronger activation only in a small area in the posterior middle temporal gyrus. These results reveal differences between two versions of the protocol and provide evidence that both are useful for language lateralization and worked well for Brazilian population. The complex version produces stronger activation in several nodes of the semantic network and therefore is elected for participants who can perform well these tasks., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimer's disease (AD) in Brazil, with special focus on cognitive disorders. It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the field. The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of cognitive disorders in AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of cognitive disorders encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine and other drugs and substances) and non-pharmacological (including cognitive rehabilitation, physical activity, occupational therapy, and music therapy) approaches. Recommendations for the treatment of behavioral and psychological symptoms of dementia due to Alzheimer's disease are included in a separate article of this edition., Competing Interests: Disclosure: The authors report no conflicts of interest.

This article reports the recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the treatment of Alzheimer's disease (AD) in Brazil, with special focus on behavioral and psychological symptoms of dementia (BPSD). It constitutes a revision and broadening of the 2005 guidelines based on a consensus involving researchers (physicians and non-physicians) in the field. The authors carried out a search of articles published since 2005 on the MEDLINE, LILACS and Cochrane Library databases. The search criteria were pharmacological and non-pharmacological treatment of the behavioral and psychological symptoms of AD. Studies retrieved were categorized into four classes, and evidence into four levels, based on the 2008 recommendations of the American Academy of Neurology. The recommendations on therapy are pertinent to the dementia phase of AD. Recommendations are proposed for the treatment of BPSD encompassing both pharmacological (including acetyl-cholinesterase inhibitors, memantine, neuroleptics, anti-depressives, benzodiazepines, anti-convulsants plus other drugs and substances) and non-pharmacological (including education-based interventions, physiotherapy, occupational therapy, music therapy, therapy using light, massage and art therapy) approaches. Recommendations for the treatment of cognitive disorders of AD symptoms are included in a separate article of this edition., Competing Interests: Disclosure: The authors reports no conflicts of interest.

Neuroanatomical correlations of naming and lexical-semantic memory are not yet fully understood. The most influential approaches share the view that semantic representations reflect the manner in which information has been acquired through perception and action, and that each brain area processes different modalities of semantic representations. Despite these anatomical differences in semantic processing, generalization across different features that have similar semantic significance is one of the main characteristics of human cognition., Methods: We evaluated the brain regions related to naming, and to the semantic generalization, of visually presented drawings of objects from the Boston Naming Test (BNT), which comprises different categories, such as animals, vegetables, tools, food, and furniture. In order to create a model of lesion method, a sample of 48 subjects presenting with a continuous decline both in cognitive functions, including naming skills, and in grey matter density (GMD) was compared to normal young adults with normal aging, amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). Semantic errors on the BNT, as well as naming performance, were correlated with whole brain GMD as measured by voxel-based morphometry (VBM)., Results: The areas most strongly related to naming and to semantic errors were the medial temporal structures, thalami, superior and inferior temporal gyri, especially their anterior parts, as well as prefrontal cortices (inferior and superior frontal gyri)., Conclusion: The possible role of each of these areas in the lexical-semantic networks was discussed, along with their contribution to the models of semantic memory organization., Competing Interests: Disclosure: The authors reports no conflicts of interest.

To evaluate hippocampal volume in patients with AD and aMCI, and correlate its atrophy with verbal episodic memory performance., Methods: We studied 42 individuals older than 50 years, including 14 with amnestic mild cognitive impairment (aMCI), 14 with mild Alzheimer's disease (AD) and 14 normal controls. All individuals were submitted to the Rey auditory verbal learning test (RAVLT) to evaluate episodic memory. They were also submitted to the forward (FDS) and backward digit span (BDS) subtest of WAIS-R to evaluate working memory and attention, and to the Mini Mental State Examination (MMSE). Hippocampal volumetric measurements were performed according to anatomic guidelines from a standard protocol using high-resolution T1-inversion recovery 3-mm coronal MRI slices. Hippocampal volumes (HV) were corrected for the variation in total intracranial volume. There was no significant difference between the three groups concerning age and education., Results: On RAVLT, there was a continuum between the three groups, with AD recalling less words, controls more, and aMCI subjects showing an intermediate performance on all sub-items. We found an asymmetry between HVs, with smaller mean left HV for all groups. ANOVA and post hoc Tukey's test for comparisons of HV showed a significant difference among groups, with difference between controls and both AD and aMCI, although there was no significant difference between AD and aMCI groups., Conclusions: There was a significant correlation between hippocampal volumes and scores on RAVLT, confirming that medial temporal structures are closely associated with memory performance in normal ageing as well as in aMCI and AD.

To study category verbal fluency (VF) for animals in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer disease (AD) and normal controls., Method: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, while aMCI was based on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent testing of category VF for animals, lexical semantic function (Boston Naming-BNT, CAMCOG Similarities item), WAIS-R forward and backward digit span, Rey Auditory Verbal Learning (RAVLT), Mini-Mental Status Examination (MMSE), and other task relevant functions such as visual perception, attention, and mood state (with Cornell Scale for Depression in Dementia). Data analysis used ANOVA and a post-hoc Tukey test for intergroup comparisons, and Pearson's coefficient for correlations of memory and FV tests with other task relevant functions (statistical significance level was p<0.05)., Results: aMCI patients had lower performance than controls on category VF for animals and on the backward digit span subtest of WAIS-R but higher scores compared with mild AD patients. Mild AD patients scored significantly worse than aMCI and controls across all tests., Conclusion: aMCI patients may have poor performance in some non-memory tests, specifically category VF for animals in our study, where this could be attributable to the influence of working memory.