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1.
Mol Psychiatry ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071110

RESUMO

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.

2.
Alzheimers Dement ; 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36150075

RESUMO

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. METHODS: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). RESULTS: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. DISCUSSION: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.

3.
Alzheimers Dement ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098676

RESUMO

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

4.
Arq Neuropsiquiatr ; 80(5 Suppl 1): 1-6, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35976294

RESUMO

Training of neurologists for the near future is a challenge due to the likely advances in neuroscientific methods, which will change much of our knowledge on diagnosis and treatment of neurological diseases. OBJECTIVE: to comment on what may be more likely to be a constant in the very near future and to recommend how to prepare the neurologist for the 21st century. METHODS: through a critical review of recent articles on the teaching of Neurology, to present a personal view on the subject. RESULTS: Diagnostic methods and therapeutic resources in Neurology will be greatly improved, but the central core of teaching young neurologists will continue to be the clinical/anatomical correlation. The neurologist must be prepared to be the primary physician in the care of patients with neurological disorders, although the roles of consultant and clinical neuroscientist must also be considered. In addition to technical knowledge, the neurologist must be prepared to discuss not only distressing issues related to the specialty, such as the risks of genetic diseases for family members of their patients, the inexorable progression of some diseases and the need for palliative care, but also problems not directly related to Neurology that cause anxiety and depression in the patient or that are the main reason for the initial consultation. CONCLUSION: neurology will be an even more important area of medicine and the neurologist must be well prepared to be the primary doctor to diagnose, treat and follow the patient with neurological disorders. In addition to technical knowledge, training in doctor-patient relations should be highlighted.


Assuntos
Doenças do Sistema Nervoso , Neurologia , Ansiedade , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Neurologistas , Neurologia/história
5.
J Glob Health ; 12: 05029, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35939273

RESUMO

Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome. Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis. Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status. Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.


Assuntos
COVID-19 , Assistência ao Convalescente , COVID-19/complicações , Estudos de Coortes , Fadiga , Feminino , Humanos , Alta do Paciente , Fatores de Risco
6.
Alzheimers Res Ther ; 14(1): 108, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932032

RESUMO

BACKGROUND: In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations. METHODS: Clinical data was collected from LatAm families at risk for DIAD. Symptomatic family members were identified and assessed by local clinicians and referred for genetic counseling and testing. To determine the likelihood of pathogenicity among variants of unknown significance from LatAm populations, we report pedigree information, frequency in control populations, in silico predictions, and cell-based models of amyloid-beta ratios. RESULTS: We identified five novel variants in the presenilin1 (PSEN1) gene from Brazilian and Mexican families. The mean age at onset in newly identified families was 43.5 years (range 36-54). PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, p.Ala275Thr, and p.Ile414Thr variants have not been reported in PubMed, ClinVar, and have not been reported in dominantly inherited AD (DIAD) families. We found that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr produce Aß profiles consistent with known AD pathogenic mutations. PSEN1 p.Ile414Thr did not alter Aß in a manner consistent with a known pathogenic mutation. CONCLUSIONS: Our study provides further insights into the genetics of AD in LatAm. Based on our findings, including clinical presentation, imaging, genetic, segregations studies, and cell-based analysis, we propose that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr are likely pathogenic variants resulting in DIAD, whereas PSEN1 p.Ile414Thr is likely a risk factor. This report is a step forward to improving the inclusion/engagement of LatAm families in research. Family discovery is of great relevance for the region, as new initiatives are underway to extend clinical trials and observational studies to families living with DIAD.


Assuntos
Doença de Alzheimer , Adulto , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Humanos , América Latina , Pessoa de Meia-Idade , Mutação/genética , Presenilina-1/genética
8.
J Alzheimers Dis ; 89(1): 181-192, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35871330

RESUMO

BACKGROUND: Previous studies of hippocampal function and volume related to episodic memory deficits in patients with amnestic mild cognitive impairment (aMCI) have produced mixed results including increased or decreased activity and volume. However, most of them have not included biomarkers, such as amyloid-ß (Aß) deposition which is the hallmark for early identification of the Alzheimer's disease continuum. OBJECTIVE: We investigated the role of Aß deposition, functional hippocampal activity and structural volume in aMCI patients and healthy elderly controls (HC) using a new functional MRI (fMRI) ecological episodic memory task. METHODS: Forty-six older adults were included, among them Aß PET PIB positive (PIB+) aMCI (N = 17), Aß PET PIB negative (PIB-) aMCI (N = 15), and HC (N = 14). Hippocampal volume and function were analyzed using Freesurfer v6.0 and FSL for news headlines episodic memory fMRI task, and logistic regression for group classification in conjunction with episodic memory task and traditional neuropsychological tests. RESULTS: The aMCI PIB+ and PIB-patients showed significantly worse performance in relation to HC in most traditional neuropsychological tests and within group difference only on story recall and the ecological episodic memory fMRI task delayed recall. The classification model reached a significant accuracy (78%) and the classification pattern characterizing the PIB+ included decreased left hippocampal function and volume, increased right hippocampal function and volume, and worse episodic memory performance differing from PIB-which showed increased left hippocampus volume. CONCLUSION: The main findings showed differential neural correlates, hippocampal volume and function during episodic memory in aMCI patients with the presence of Aß deposition.


Assuntos
Doença de Alzheimer , Amiloidose , Disfunção Cognitiva , Memória Episódica , Idoso , Doença de Alzheimer/patologia , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloidose/patologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Testes Neuropsicológicos
10.
Rev Saude Publica ; 56: 38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35649085

RESUMO

OBJECTIVE: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS: In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION: Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.


Assuntos
Microcefalia , Adulto , Idoso , Encéfalo , Brasil/epidemiologia , Cefalometria , Cabeça/anatomia & histologia , Humanos , Masculino , Microcefalia/complicações , Microcefalia/diagnóstico , Microcefalia/epidemiologia
11.
Dement Neuropsychol ; 16(1): 79-88, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719263

RESUMO

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


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

12.
Neurobiol Aging ; 117: 107-116, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35709536

RESUMO

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 ± 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease (p = 0.039, p = 0.003, and p = 0.003 respectively); LLD, and DS were associated with brain infarcts (p = 0.012, p = 0.018, respectively) and Lewy body disease (p = 0.043, p = 0.002, respectively). DS was associated with beta-amyloid plaque burden (p = 0.027) and cerebral amyloid angiopathy (p = 0.035) in cognitively normal individuals (Clinical Dementia Rating scale = 0). Vascular brain pathology was the strongest correlate of clinical depictions of depression in the absence of dementia, corroborating the vascular hypothesis of depression. Lewy body pathology underlay DS. An older adult with DS or LLD should be monitored for possible cognitive decline or neurodegenerative disorders.


Assuntos
Doença de Alzheimer , Demência , Transtorno Depressivo Maior , Doença por Corpos de Lewy , Idoso , Doença de Alzheimer/patologia , Encéfalo/patologia , Demência/patologia , Depressão , Transtorno Depressivo Maior/patologia , Humanos , Corpos de Lewy/patologia , Doença por Corpos de Lewy/patologia , Placa Amiloide/patologia
13.
Psychol Med ; 52(12): 2387-2398, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35521752

RESUMO

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

14.
Arq. neuropsiquiatr ; 80(5,supl.1): 1-6, May 2022.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1393942

RESUMO

Abstract Training of neurologists for the near future is a challenge due to the likely advances in neuroscientific methods, which will change much of our knowledge on diagnosis and treatment of neurological diseases. Objective: to comment on what may be more likely to be a constant in the very near future and to recommend how to prepare the neurologist for the 21st century. Methods: through a critical review of recent articles on the teaching of Neurology, to present a personal view on the subject. Results: Diagnostic methods and therapeutic resources in Neurology will be greatly improved, but the central core of teaching young neurologists will continue to be the clinical/anatomical correlation. The neurologist must be prepared to be the primary physician in the care of patients with neurological disorders, although the roles of consultant and clinical neuroscientist must also be considered. In addition to technical knowledge, the neurologist must be prepared to discuss not only distressing issues related to the specialty, such as the risks of genetic diseases for family members of their patients, the inexorable progression of some diseases and the need for palliative care, but also problems not directly related to Neurology that cause anxiety and depression in the patient or that are the main reason for the initial consultation. Conclusion: neurology will be an even more important area of medicine and the neurologist must be well prepared to be the primary doctor to diagnose, treat and follow the patient with neurological disorders. In addition to technical knowledge, training in doctor-patient relations should be highlighted.


Resumo A formação do neurologista para o futuro próximo é um desafio devido aos prováveis avanços nos métodos da neurociência, que mudarão muito do nosso conhecimento sobre diagnóstico e tratamento de doenças neurológicas. Objetivo: comentar o que pode ser mais constante no futuro próximo e propor como preparar o neurologista para o século XXI. Métodos: por meio de uma revisão crítica de artigos recentes sobre o ensino da Neurologia, apresentar uma visão pessoal sobre o assunto. Resultados: Os métodos diagnósticos e os recursos terapêuticos em Neurologia serão muito aprimorados, mas o núcleo central do ensino de jovens neurologistas continuará sendo a correlação clínico-anatômica. O neurologista deve estar preparado para ser o médico principal no atendimento de pacientes com distúrbios neurológicos, embora os papéis de consultor e neurocientista clínico também devam ser considerados. Além do conhecimento técnico, o neurologista deve estar preparado para discutir não apenas questões angustiantes relacionadas à especialidade, como os riscos de doenças genéticas para os familiares de seus pacientes, a progressão inexorável de algumas doenças e a indicação de cuidados paliativos, mas também problemas não diretamente relacionados à Neurologia que causam ansiedade e depressão no paciente ou que são a principal causa da consulta. Conclusão: a neurologia será uma área ainda mais importante da medicina e o neurologista deve estar bem-preparado para ser o médico principal para diagnosticar, tratar e acompanhar o paciente com distúrbios neurológicos. Além do conhecimento técnico, a formação humanística deve ter destaque.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35633395

RESUMO

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

16.
Gen Hosp Psychiatry ; 75: 38-45, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35134702

RESUMO

OBJECTIVE: The present study aims to investigate the occurrence of psychiatric and cognitive impairments in a cohort of survivors of moderate or severe forms of COVID-19. METHOD: 425 adults were assessed 6 to 9 months after hospital discharge with a structured psychiatric interview, psychometric tests and a cognitive battery. A large, multidisciplinary, set of clinical data depicting the acute phase of the disease, along with relevant psychosocial variables, were used to predict psychiatric and cognitive outcomes using the 'Least Absolute Shrinkage and Selection Operator' (LASSO) method. RESULTS: Diagnoses of 'depression', 'generalized anxiety disorder' and 'post-traumatic stress disorder' were established respectively in 8%, 15.5% and 13.6% of the sample. After pandemic onset (i.e., within the previous year), the prevalence of 'depression' and 'generalized anxiety disorder' were 2.56% and 8.14%, respectively. Memory decline was subjectively reported by 51.1% of the patients. Psychiatric or cognitive outcomes were not associated with any clinical variables related to the severity of acute-phase disease, nor by disease-related psychosocial stressors. CONCLUSIONS: This is the first study to access rates of psychiatric and cognitive morbidity in the long-term outcome after moderate or severe forms of COVID-19 using standardized measures. As a key finding, there was no significant association between clinical severity in the acute-phase of SARS-CoV-2 infection and the neuropsychiatric impairment 6 to 9 months thereafter.


Assuntos
COVID-19 , Adulto , Ansiedade , COVID-19/epidemiologia , Cognição , Estudos de Coortes , Depressão , Humanos , Morbidade , SARS-CoV-2
17.
Alzheimers Dement ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978148

RESUMO

INTRODUCTION: Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. METHODS: In this cross-sectional study, cognitive function was assessed by the Clinical Dementia Rating sum of boxes (CDR-SOB). We investigated the association of occupation complexity and education with CDR-SOB using adjusted linear regression models for age, sex, and neuropathological lesions. RESULTS: In 1023 participants, 77% had < 5 years of education, and 56% unskilled occupations. Compared to the group without education, those with formal education had lower CDR-SOB (1-4 years: ß = -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; ≥5 years: ß = -1.42, 95% CI = -2.47; -0.38, P = .008). Occupation complexity and demands were unrelated to cognition. DISCUSSION: Education, but not occupation, was related to better cognitive abilities independent of the presence of neuropathological insults.

18.
Alzheimer Dis Assoc Disord ; 36(2): 156-161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35001032

RESUMO

OBJECTIVE: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. METHODS: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. RESULTS: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. CONCLUSION: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.


Assuntos
Doença de Alzheimer , Aterosclerose , Demência Vascular , Doença por Corpos de Lewy , Pneumonia , Envelhecimento/patologia , Doença de Alzheimer/psicologia , Autopsia , Bancos de Espécimes Biológicos , Brasil , Causas de Morte , Demência Vascular/diagnóstico , Humanos , Doença por Corpos de Lewy/diagnóstico
19.
Alzheimers Dement ; 18(4): 581-590, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34338427

RESUMO

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


Assuntos
Disfunção Cognitiva , Demência , Idoso , Brasil/epidemiologia , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Demência/epidemiologia , Demência/psicologia , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de Risco
20.
Aging Cell ; 21(1): e13521, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894056

RESUMO

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post-mortem human brain tissue of elderly. We identified a significant loss of lamin-B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin-B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post-mortem human tissue from non-demented elderly. The lamin-B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin-B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra-regional-dependent aging response of human astrocytes. Moreover, we described senescence-associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin-B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging.


Assuntos
Astrócitos/metabolismo , Hipocampo/fisiopatologia , Lamina Tipo B/metabolismo , Animais , Senescência Celular , Humanos , Camundongos
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