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1.
Sci Rep ; 14(1): 6287, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491154

RESUMO

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread ß-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of ß-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Cebinae , Humanos , Animais , Camundongos , Idoso , Doença de Alzheimer/patologia , Cebus , Haplorrinos , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Placa Amiloide/patologia , Proteínas tau/metabolismo
2.
Mov Disord Clin Pract ; 11(3): 238-247, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38155526

RESUMO

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


Assuntos
Degeneração Corticobasal , Tauopatias , Humanos , Fluordesoxiglucose F18/metabolismo , Tauopatias/metabolismo , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Atrofia/metabolismo
3.
Cereb Circ Cogn Behav ; 5: 100191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38046105

RESUMO

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

4.
Res Sq ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38106066

RESUMO

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using non-human primates in studies, they can bridge mouse models and humans, as non-human primates are phylogenetically close to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed three capuchin brains using structural 7T MRI and neuropathological evaluation. Alzheimer-type pathology was found in one case. Widespread ß-amyloid pathology mainly in the form of focal deposits with variable morphology and high density of mature plaques. Noteworthy, plaque-associated dystrophic neurites, associated with disrupted of axonal transport and early cytoskeletal alteration, were frequently found. Unlike other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of ß-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Besides, astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. Aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease.

5.
Arq Neuropsiquiatr ; 81(12): 1070-1076, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38157874

RESUMO

BACKGROUND: Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases. OBJECTIVE: To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD. METHODS: A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021. RESULTS: The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD. CONCLUSION: The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.


ANTECEDENTES: A doença de Alzheimer (DA) foi descrita em 1907 e, desde então, deixou de ser relativamente rara para se tornar uma das doenças mais prevalentes. OBJETIVO: Descrever a evolução das noções sobre demências e DA e investigar as razões do aumento do interesse científico pela DA. MéTODOS: Foi realizada uma análise histórica dos conhecimentos sobre demência, o local da atividade mental, as relações entre doenças cerebrais e a atividade mental, e sobre os avanços na pesquisa sobre a DA, desde a sua descoberta até a publicação da hipótese da cascata amiloide em 1992. Foi realizada uma busca na Biblioteca Nacional de Medicina dos Estados Unidos da América (PubMed) por artigos científicos que incluíssem os termos demência ou DA nos 50 anos, de 1972 a 2021. RESULTADOS: A pesquisa científica sobre DA aumentou de 615 artigos com o termo doença de Alzheimer na primeira década (1972-1981), para 100.028 artigos na última década (2012-2021): um aumento de 162,6 vezes enquanto as publicações com o termo demência aumentaram 28,6 vezes no mesmo período. Nas décadas de 1960 e 1970, chegou-se a um consenso de que a DA é responsável pela maioria dos casos de demência, anteriormente conhecida como demência senil. Na década de 1980, o peptídeo beta-amiloide foi identificado no núcleo da placa senil, a proteína tau hiperfosforilada foi encontrada em emaranhados neurofibrilares e uma mutação foi descoberta em uma forma hereditária de DA. CONCLUSãO: A expansão do conceito de DA para incluir a demência senil e as descobertas ocorridas na década de 1980 ampliaram enormemente a pesquisa em DA.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Emaranhados Neurofibrilares/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo
6.
Arq. neuropsiquiatr ; 81(12): 1070-1076, Dec. 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527915

RESUMO

Abstract Background Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases. Objective To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD. Methods A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021. Results The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD. Conclusion The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.


Resumo Antecedentes A doença de Alzheimer (DA) foi descrita em 1907 e, desde então, deixou de ser relativamente rara para se tornar uma das doenças mais prevalentes. Objetivo Descrever a evolução das noções sobre demências e DA e investigar as razões do aumento do interesse científico pela DA. Métodos Foi realizada uma análise histórica dos conhecimentos sobre demência, o local da atividade mental, as relações entre doenças cerebrais e a atividade mental, e sobre os avanços na pesquisa sobre a DA, desde a sua descoberta até a publicação da hipótese da cascata amiloide em 1992. Foi realizada uma busca na Biblioteca Nacional de Medicina dos Estados Unidos da América (PubMed) por artigos científicos que incluíssem os termos demência ou DA nos 50 anos, de 1972 a 2021. Resultados A pesquisa científica sobre DA aumentou de 615 artigos com o termo doença de Alzheimer na primeira década (1972-1981), para 100.028 artigos na última década (2012-2021): um aumento de 162,6 vezes enquanto as publicações com o termo demência aumentaram 28,6 vezes no mesmo período. Nas décadas de 1960 e 1970, chegou-se a um consenso de que a DA é responsável pela maioria dos casos de demência, anteriormente conhecida como demência senil. Na década de 1980, o peptídeo beta-amiloide foi identificado no núcleo da placa senil, a proteína tau hiperfosforilada foi encontrada em emaranhados neurofibrilares e uma mutação foi descoberta em uma forma hereditária de DA. Conclusão A expansão do conceito de DA para incluir a demência senil e as descobertas ocorridas na década de 1980 ampliaram enormemente a pesquisa em DA.

7.
Acta Neuropathol Commun ; 11(1): 205, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115150

RESUMO

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.


Assuntos
Doença de Alzheimer , Arteriosclerose , Angiopatia Amiloide Cerebral , Doença por Corpos de Lewy , Acidente Vascular Cerebral Lacunar , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Doença de Alzheimer/patologia , Apolipoproteína E4/genética , Apolipoproteínas E/metabolismo , Arteriosclerose/genética , Autopsia , Angiopatia Amiloide Cerebral/genética , Cognição , Proteínas de Ligação a DNA/genética , Genótipo , Doença por Corpos de Lewy/genética , Acidente Vascular Cerebral Lacunar/genética
8.
Alzheimers Dement (N Y) ; 9(3): e12425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744309

RESUMO

Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population. Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

9.
Curr Alzheimer Res ; 20(5): 341-349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37587822

RESUMO

BACKGROUND: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders. OBJECTIVE: The objectibe of this study is to investigate the value of the ACE-R combined with sociodemographic factors in the differential diagnosis between AD and bvFTD. METHODS: The ACE-R was administered to 102 patients with mild dementia due to probable AD, 37 with mild bvFTD, and 135 controls. Performances of patients and controls were analyzed by logistic regression and by ROC curves to refine the diagnostic accuracy of the ACE-R in AD and bvFTD. RESULTS: The ACE-R subscores Attention and Orientation, Fluency, and Memory, in combination with schooling differentiated AD from controls with an area under the ROC curve (AUC) of 0.936 (86% sensitivity and 87% specificity). The ACE-R subscores Attention and Orientation, Fluency, and Language, in combination with sex (male), age, and schooling, discriminated bvFTD from controls with an AUC of 0.908 (81% sensitivity and 95% specificity). In the differentiation between AD and bvFTD, the ACE-R subscores Attention and Orientation, Fluency, and Language, together with age, displayed an AUC of 0.865 (78% sensitivity and 85% specificity). CONCLUSION: The combination of ACE-R scores with sociodemographic data allowed good differentiation between AD and bvFTD in the study sample.

10.
J Stroke Cerebrovasc Dis ; 32(9): 107229, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37531722

RESUMO

INTRODUCTION: Apolipoprotein E (APOE) ε4 allele has been associated with higher carotid atherosclerosis risk, while the APOE-ε2 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric measurements of carotid atherosclerosis in an autopsy study with an admixed sample. METHODS: We measured the intima-media thickness (IMT) and stenosis of the common (CCA) and internal carotid (ICA) arteries. The APOE polymorphisms were determined by real-time polymerase chain reaction. Participants were classified into three groups according to the APOE alleles (ε2, ε3, and ε4). We evaluated the association between APOE groups and carotid atherosclerosis using adjusted regression models and included interaction terms of APOE alleles with age, sex, and race. RESULTS: We evaluated 1,850 carotid artery samples from 185 participants (mean age=75±12 years old, 55% female, and 71% White). The APOE-ε2 group (n=17) had a lower carotid obstruction and a lower number of severe stenoses (≥ 70%). Having at least one ε4 allele (n=51) was not associated with carotid atherosclerosis. APOE alleles were also not associated with carotid IMT. Age, sex, and race did not modify these relationships. CONCLUSION: APOE-ε2 carriers had a lower percentage of carotid obstruction and less severe stenosis. APOE-ε4 was not related to a higher risk of carotid atherosclerosis in this cross-sectional population-based autopsy study.


Assuntos
Apolipoproteínas E , Doenças das Artérias Carótidas , Trombose , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Apolipoproteína E2 , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Autopsia , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/genética , Espessura Intima-Media Carotídea , Constrição Patológica , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Fatores de Risco
11.
J Psychiatr Res ; 164: 329-334, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37393798

RESUMO

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.


Assuntos
Transtorno Bipolar , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Análise em Microsséries , Regulação da Expressão Gênica , Expressão Gênica/genética , Hipocampo/metabolismo
12.
Front Neurol ; 14: 1198869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497015

RESUMO

Alzheimer's disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic conditions, which create unique challenges to AD diagnosis and management. To address these issues, the Americas Health Foundation convened a panel of eight neurologists, geriatricians, and psychiatrists from Argentina, Brazil, Colombia, Ecuador, Guatemala, Mexico, and Peru who are experts in AD for a three-day virtual meeting to discuss best practices for AD diagnosis and treatment in LAC and create a manuscript offering recommendations to address identified barriers. In LAC, several barriers hamper diagnosing and treating people with dementia. These barriers include access to healthcare, fragmented healthcare systems, limited research funding, unstandardized diagnosis and treatment, genetic heterogeneity, and varying social determinants of health. Additional training for physicians and other healthcare workers at the primary care level, region-specific or adequately adapted cognitive tests, increased public healthcare insurance coverage of testing and treatment, and dedicated search strategies to detect populations with gene variants associated with AD are among the recommendations to improve the landscape of AD.

13.
Arq Neuropsiquiatr ; 81(7): 632-640, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37494948

RESUMO

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


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


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Humanos , Demência Frontotemporal/diagnóstico , Doença de Alzheimer/diagnóstico , Brasil , Diagnóstico Diferencial , Biomarcadores
14.
Arq. neuropsiquiatr ; 81(7): 632-640, July 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1505754

RESUMO

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


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

15.
Dement Neuropsychol ; 17: e20220064, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261255

RESUMO

Subjective cognitive decline is defined as a self-perceived cognitive decline but with normal performance in neuropsychological assessments. Objective: To verify the evolution of patients diagnosed with subjective cognitive decline compared to the cognitively normal group without any concern. Methods: This is a follow-up study based on data analysis from the Tremembé epidemiologic study, in Brazil. The 211 individuals classified as cognitively normal and 174 diagnosed as having subjective cognitive decline at baseline were invited to participate. Results: After a median follow-up time of five years, 108 subjective cognitive decline participants (62.0%) were reassessed. Of these, 58 (53.7%) kept this diagnosis, whereas 14 individuals (12.9%) progressed to mild cognitive impairment and 5 (4.6%) to dementia. In the cognitively normal group, 107 (50.7%) were reassessed, of which 51 (47.7%) were still classified likewise, 6 (5.6%) evolved to mild cognitive impairment and 9 (8.4%) to dementia. The presence of cognitive decline had a significant association with increasing age and depression symptoms. Considering the total number of baseline participants in each group: the subjective cognitive decline group showed higher percentage of mild cognitive impairment (p=0.022) and no difference was found in progression to dementia (p=0.468) between the groups after follow-up assessment. Conclusion: Most subjective cognitive decline participants at baseline kept their cognitive complaint at follow-up and this group progressed more to mild cognitive impairment than the other group. No difference in the progression to dementia was found, despite the higher incidence of dementia in the cognitively normal group.


O declínio cognitivo subjetivo (DCS) é definido como autopercepção de declínio cognitivo, mas com desempenho normal nas avaliações neuropsicológicas. Objetivo: O objetivo foi verificar a evolução dos pacientes diagnosticados com DCS em relação ao grupo cognitiva mente normal (CN), sem qualquer queixa. Métodos: Trata-se de um estudo de seguimento baseado na análise de dados do estudo epidemiológico de Tremembé, Brasil. Os 211 indivíduos classificados como CN e os 174 diagnosticados como DCS na fase inicial do estudo foram convidados a participar. Resultados: Após o tempo médio de seguimento de cinco anos, 108 participantes da DCS (62,0%) foram reavaliados. Deles, 58 (53,7%) mantiveram o diagnóstico de DCS, enquanto 14 (12,9%) evoluíram para comprometimento cognitivo leve (CCL) e cinco (4,6%) para demência. No grupo CN, 107 (50,7%) foram reavaliados, dos quais 51 (47,7%) ainda foram classificados como CN, seis (5,6%) evoluíram para CCL e nove (8,4%) para demência. A presença de declínio cognitivo teve associação significativa com o aumento da idade e com sintomas de depressão. Considerando-se o número total de participantes da fase inicial do estudo de cada grupo: o grupo DCS apresentou maior percentual de CCL (p=0,022) e não houve diferença na progressão para demência (p=0,468) entre ambos os grupos após a avaliação de seguimento. Conclusão: A maioria dos participantes DCS da fase inicial do estudo manteve sua queixa cognitiva no seguimento, e esse grupo progrediu mais para CCL. Não foi encontrada diferença na progressão para demência, apesar da maior incidência de demência no grupo CN.

16.
Front Immunol ; 14: 1174020, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287969

RESUMO

Objective: To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. Methods: We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers. Results: Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings. Conclusion: Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.


Assuntos
COVID-19 , Disfunção Cognitiva , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , SARS-CoV-2 , Síndrome Pós-COVID-19 Aguda , Disfunção Cognitiva/epidemiologia , Citocinas
17.
Arq Neuropsiquiatr ; 81(5): 433-443, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37257463

RESUMO

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


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


Assuntos
Substância Cinzenta , Futebol , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Substância Cinzenta/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Glucose , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons
18.
J Alzheimers Dis ; 93(4): 1307-1316, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182864

RESUMO

BACKGROUND: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. OBJECTIVE: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. METHODS: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. RESULTS: In 253 participants (mean age = 78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (OR = 0.85, 95% CI = 0.69; 1.06, p = 0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (OR = 4.02, 95% CI = 1.39; 11.6, p = 0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (OR = 0.83, 95% CI = 0.60; 1.16, p = 0.28). CONCLUSION: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Disfunção Cognitiva , Doença da Artéria Coronariana , Humanos , Masculino , Idoso de 80 Anos ou mais , Idoso , Feminino , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doenças Cardiovasculares/complicações , Viés de Seleção , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Aterosclerose/complicações
19.
Alzheimers Dement ; 19(9): 4046-4060, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37204054

RESUMO

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.


Assuntos
Disfunção Cognitiva , Humanos , América Latina , Disfunção Cognitiva/prevenção & controle , Estilo de Vida , Cognição , Projetos de Pesquisa
20.
Arq. neuropsiquiatr ; 81(5): 433-443, May 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447405

RESUMO

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


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

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