Pesquisa | SciELO

Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen’s d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

https://doi.org/10.47626/1516-4446-2022-2767

Discourse abilities in euthymic elderly patients with bipolar disorder: a preliminary study
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Valeriano, Maria Gabriela

; Alegria, Renné

; Forlenza, Orestes Vicente

; Radanovic, Marcia

Dementia & Neuropsychologia

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2023, Volume 17 elocation e20220067

Resumo: En Pt | Texto: En Pt | PDF: En | PDF: Pt

ABSTRACT Cognitive impairment has been well described in euthymic patients with bipolar disorder (BD), as well as in elderly patients. Language disturbances are less studied, and several inconsistencies are reported in the literature. Most language studies focus on verbal fluency and semantic alterations, with a lack of studies addressing discursive abilities in BD. Objective: The aim of this study was to evaluate discourse abilities in euthymic elderly individuals with BD. Methods: We studied 19 euthymic elderly patients with BD and a control group of non-BD, which performed a cognitive assessment of attention, memory, executive functions, and visual abilities. All participants produced a description from the Cookie Theft Picture in oral and written modalities that was analyzed according to micro- and macrolinguistic aspects. Generalized linear models were performed to compare intergroup linguistic performance and to determine whether any cognitive domain was associated with linguistic outcomes. Results: The BD group produced more cohesion errors in the oral and written modalities (p=0.016 and p=0.011, respectively) and fewer thematic units in the oral modality (p=0.027) than the control group. Conclusions: BD patients presented minimal changes in the descriptive discourse task. The BD group produced more cohesion errors than the control group in the oral (p=0.016) and written discourse (p=0.011); also, the BD group produced fewer thematic units than controls in the oral discourse (p=0.027).

RESUMO Déficits cognitivos têm sido descritos em pacientes com transtorno bipolar (TB) em fase eutímica, bem como em idosos. Alterações linguísticas são menos estudadas, e os achados de literatura são inconsistentes. A maioria dos estudos em linguagem baseia-se em avaliações de fluência verbal e alterações semânticas, havendo escassez de trabalhos que abordem as habilidades discursivas no TB. Objetivo: Avaliar as habilidades discursivas em indivíduos idosos eutímicos com TB. Métodos: Estudamos 19 pacientes idosos eutímicos com TB e um grupo de idosos sem TB e cognitivamente saudáveis, que realizaram avaliação cognitiva da atenção, memória, funções executivas e habilidades visuoespaciais. Todos os participantes produziram uma descrição da Prancha do Roubo dos Biscoitos nas modalidades oral e escrita, que foram analisadas de acordo com aspectos micro e macrolinguísticos. Análises por meio de modelos lineares generalizados foram realizados para comparar o desempenho linguístico entre os grupos e para determinar se algum domínio cognitivo estava associado a esse desempenho. Resultados: O grupo TB produziu mais erros de coesão nas modalidades oral e escrita (p=0,016 e p=0,011, respectivamente) e menos unidades temáticas na modalidade oral (p=0,027) do que o grupo controle. Conclusão: Os pacientes com TB apresentaram alterações leves na tarefa discursiva. O grupo TB produziu maior número de erros de coesão do que o grupo controle no discurso oral (p=0,016) e escrito (p=0,011). Além disso, o grupo TB produziu menor número de unidades temáticas do que os controles na tarefa de discurso oral (p=0,027).

https://doi.org/10.1590/1980-5764-dn-2022-0067

Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review
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Stella, Florindo

; Radanovic, Márcia

; Gallucci-Neto, José

; Forlenza, Orestes Vicente

Dementia & Neuropsychologia

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2023, Volume 17 elocation e20230007

Resumo: En Pt | Texto: En Pt | PDF: En | PDF: Pt

ABSTRACT Behavioral disturbances are clinically relevant in patients with dementia, and pharmacological regimens to mitigate these symptoms have provided limited results. Proven to be effective in several psychiatric conditions, electroconvulsive therapy is a potentially beneficial strategy for treating severe agitation due to dementia. Objective: This review aimed to examine the publications on the efficacy, safety and tolerability of electroconvulsive therapy in treating patients with agitation due to dementia. Methods: We performed a systematic analysis on the electroconvulsive therapy to treat patients with dementia and coexisting severe agitation. Articles were classified according to the level of evidence based on methodological design. Patients received an acute course of electroconvulsive therapy, often followed by maintenance intervention. Results: We selected 19 studies (156 patients; 64.1% women; 51–98 years old), which met the inclusion criteria: one case-control study by chart analysis (level of evidence 2); one open-label study (level of evidence 3); three historical/retrospective chart analyses (level of evidence 4); and 14 case series/reports (level of evidence 5). No randomized, sham-controlled clinical trials (level of evidence 1) were identified, which represents the main methodological weakness. Some patients had postictal delirium, cardiovascular decompensation and cognitive changes, lasting for a short time. Conclusions: Overall, patients achieved significant improvement in agitation. However, the main finding of the present review was the absence of methodological design based on randomized and sham-controlled clinical trials. Despite methodological limitations and side effects requiring attention, electroconvulsive therapy was considered a safe and effective treatment of patients with severe agitation and related behavioral disorders due to dementia.

RESUMO Distúrbios comportamentais são clinicamente relevantes em pacientes com demência, e regimes farmacológicos para mitigar esses sintomas têm proporcionado resultados limitados. Comprovadamente eficaz em diversas condições psiquiátricas, a eletroconvulsoterapia é uma estratégia potencialmente benéfica para o tratamento de pacientes com agitação grave na demência. Objetivos: Esta revisão examina as publicações sobre eficácia, segurança e tolerabilidade da eletroconvulsoterapia no tratamento de pacientes com agitação na demência. Métodos: Realizamos uma análise sistemática da eletroconvulsoterapia no tratamento de pacientes com demência e agitação grave. Os artigos foram classificados quanto ao nível de evidência com base no delineamento metodológico. Os pacientes receberam um curso agudo de eletroconvulsoterapia, frequentemente seguido de manutenção. Resultados: Foram selecionados 19 estudos (156 pacientes; 64,1% mulheres; 51–98 anos): um estudo caso-controle desenvolvido com base na análise de prontuários (nível de evidência 2); um estudo aberto (nível de evidência 3); três estudos de análise retrospectiva de prontuários (nível de evidência 4); e 14 séries/relatos de casos (nível de evidência 5). Não foram identificados ensaios clínicos randomizados e controlados com placebo (nível de evidência 1), fator que representa a principal fragilidade metodológica. No entanto, o principal achado da presente revisão consistiu na ausência de desenho metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Em geral, os efeitos colaterais foram transitórios e bem tolerados. Alguns pacientes apresentaram delirium pós-ictal, descompensação cardiovascular e alterações cognitivas por períodos breves. Conclusões: No geral, os pacientes obtiveram melhora significativa na agitação. No entanto, o principal achado da presente revisão foi a ausência de delineamento metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Apesar das limitações metodológicas e dos efeitos adversos, a eletroconvulsoterapia foi considerada um tratamento seguro e eficaz em pacientes com agitação grave e com outros distúrbios comportamentais clinicamente relevantes na demência.

https://doi.org/10.1590/1980-5764-dn-2023-0007

Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer’s disease
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Carneiro, Camila de Godoi

; Faria, Daniele de Paula

; Coutinho, Artur Martins

; Ono, Carla Rachel

; Duran, Fábio Luís de Souza

; da Costa, Naomi Antunes

; Garcez, Alexandre Teles

; da Silveira, Paula Squarzoni

; Forlenza, Orestes Vicente

; Brucki, Sonia Maria Dozzi

; Nitrini, Ricardo

; Busatto Filho, Geraldo

; Buchpiguel, Carlos Alberto

Brazilian Journal of Psychiatry

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Out 2022, Volume 44 Nº 5 Páginas 495 - 506

Resumo: En | Texto: En | PDF: En

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer’s disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer’s disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer’s disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer’s disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

https://doi.org/10.47626/1516-4446-2021-2374

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia Alzheimer
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Schilling, Lucas Porcello

; Balthazar, Marcio Luiz Figueredo

; Radanovic, Márcia

; Forlenza, Orestes Vicente

; Silagi, Marcela Lima

; Smid, Jerusa

; Barbosa, Breno José Alencar Pires

; Frota, Norberto Anízio Ferreira

; Souza, Leonardo Cruz de

; Vale, Francisco Assis Carvalho

; Caramelli, Paulo

; Bertolucci, Paulo Henrique Ferreira

; Chaves, Márcia Lorena Fagundes

; Brucki, Sonia Maria Dozzi

; Damasceno, Benito Pereira

; Nitrini, Ricardo

Dementia & Neuropsychologia

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Set 2022, Volume 16 Nº 3 Páginas 25 - 39

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

RESUMO Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa. (DA Brasil primária terciária atípica clínica funcional neuroimagem apresentada

ABSTRACT 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. Alzheimers Alzheimer s (AD Brazil primary secondary levels scenario cognitive tests conditions

https://doi.org/10.1590/1980-5764-dn-2022-s102pt

Anti-amyloid agents for treating incipient Alzheimer’s disease: a new hope?
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Loureiro, Julia C.

; Silva, Luiz Fernando A.L.

; Pais, Marcos V.

; Forlenza, Orestes V.

Brazilian Journal of Psychiatry

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Ago 2022, Volume 44 Nº 4 Páginas 368 - 369

Resumo: En | Texto: En | PDF: En

https://doi.org/10.47626/1516-4446-2022-2503

Decision tree-based classification as a support to diagnosis in the Alzheimer’s disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis
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Costa, Alana

; Pais, Marcos

; Loureiro, Júlia

; Stella, Florindo

; Radanovic, Márcia

; Gattaz, Wagner

; Forlenza, Orestes

; Talib, Leda

Brazilian Journal of Psychiatry

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Ago 2022, Volume 44 Nº 4 Páginas 370 - 377

Resumo: En | Texto: En | PDF: En

Objective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer’s disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aβ1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

https://doi.org/10.47626/1516-4446-2021-2277

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review
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Stella, Florindo

; Valiengo, Leandro C. Lane

; Paula, Vanessa J. R. de

; Lima, Carlos Augusto de Mendonça

; Forlenza, Orestes V.

Trends in Psychiatry and Psychotherapy

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Dez 2021, Volume 43 Nº 4 Páginas 243 - 255

Resumo: En | Texto: En | PDF: En

Abstract Introduction Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and causing increased burden and morbidity. Clinical presentations are pleomorphic and clinical management often requires combinations of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse psychotropic drug events emphasize the need for novel therapeutic options. Objectives To review the evidence supporting use of medical cannabinoids for treatment of neuropsychiatric symptoms (NPS) of dementia. Methods We conducted a systematic review of the medical literature to examine scientific publications reporting use of medical cannabinoids for treatment of NPS. Medical Subject Headings (MeSH) were used to search for relevant publications and only papers reporting original clinical information were included. A secondary search was performed within selected publications to capture relevant citations that were not retrieved by the systematic review. The papers selected were categorized according to the level of evidence generated by the studies in relation to this clinical application, i.e. (1) controlled clinical trials; (2) open-label or observational studies; and (3) case reports. Results Fifteen publications with original clinical data were retrieved: five controlled clinical trials, three open-label/observational studies, and seven case reports. Most studies indicated that use of medical cannabinoids engendered favorable outcomes for treatment of NPS related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior, sleep disorder, and sexual disinhibition. Conclusion Medical cannabinoids constitute a promising pharmacological approach to treatment of NPS with preliminary evidence of benefit in at least moderate to severe dementia. Controlled trials with longitudinal designs and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration, and concentrations of active compounds (e.g., cannabidiol [CBD]/ Δ9-tetrahydrocannabinol [THC] ratio) in commercial preparations of medical cannabinoids.

https://doi.org/10.47626/2237-6089-2021-0288

Mental health interventions following COVID-19 and other coronavirus infections: a systematic review of current recommendations and meta-analysis of randomized controlled trials
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Damiano, Rodolfo F.

; Di Santi, Talita

; Beach, Scott

; Pan, Pedro M.

; Lucchetti, Alessandra L.

; Smith, Felicia A.

; Forlenza, Orestes V.

; Fricchione, Gregory L.

; Miguel, Eurípedes C.

; Lucchetti, Giancarlo

Brazilian Journal of Psychiatry

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Dez 2021, Volume 43 Nº 6 Páginas 665 - 678

Resumo: En | Texto: En | PDF: En

Objective: To review the most common mental health strategies aimed at alleviating and/or preventing mental health problems in individuals during the coronavirus disease 2019 (COVID-19) and other coronavirus pandemics. Methods: We conducted a systematic review of the literature assessing three databases (PubMed, SCOPUS, and PsycINFO). A meta-analysis was performed with data from randomized controlled trials (RCTs). For non-RCT studies, a critical description of recommendations was performed. Results: From a total of 2,825 articles, 125 were included. Of those, three RCTs were included in the meta-analysis. The meta-analysis revealed that the interventions promoted better overall mental health outcomes as compared to control groups (standardized mean difference [SMD] = 0.87 [95%CI 0.33-1.41], p < 0.001, I2 = 69.2%), but did not specifically improve anxiety (SMD = 0.98 [95%CI -0.17 to 2.13], p > 0.05; I2 = 36.8%). Concerning the systematic review, we found a large body of scientific literature proposing recommendations involving psychological/psychiatric interventions, self-care, education, governmental programs, and the use of technology and media. Conclusions: We found a large body of expert recommendations that may help health practitioners, institutional and governmental leaders, and the general population cope with mental health issues during a pandemic or a crisis period. However, most articles had a low level of evidence, stressing the need for more studies with better design (especially RCTs) investigating potential mental health interventions during COVID-19. PROSPERO registration: CRD42020190212.

https://doi.org/10.1590/1516-4446-2020-1582

10.

COMVC-19: A Program to protect healthcare workers’ mental health during the COVID-19 Pandemic. What we have learned
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Fukuti, Pedro

; Uchôa, Caroline Louise Mesquita

; Mazzoco, Marina Flaborea

; Cruz, Isabella D'Andrea Garcia da

; Echegaray, Mariana V.F.

; Humes, Eduardo de Castro

; Silveira, Júlia Belizário

; Santi, Talita Di

; Miguel, Euripedes Constantino

; Corchs, Felipe

; Fatori, Daniel

; Campello, Guilherme

; Oliveira, Gabriel M. de

; Argolo, Felipe C.

; Ferreira, Felipe de M.

; Machado, Gustavo

; Argeu, Adriana

; Oliveira, Graça Maria Ramos de

; Serafim, Antônio de Pádua

; Siqueira, Luciana de Lima

; Rossi, Luciane de

; Rios, Izabel Cristina

; Oliveira, Talita Rodrigues de

; Antoniazzi, Leilane C. K.

; Gagliotti, Daniel Augusto Mori

; Abelama Neto, Emílio

; Oliveira Junior, Paulo Novais de

; Correia, Aline Villalobo

; Gonçalves, Luca Schilling

; Tortato, Liana Silva

; Busato, Wagner Machado Moraes

; Guimarães-Fernandes, Flávio

; Alves, Marcos

; Leite Netto, Oswaldo Ferreira

; Schoueri, Patrícia de Campos Lindenberg

; Roque, Márcio de Assis

; Merlin, Silvia Stahl

; Boer, Giovana Cardoso Machado

; Sallet, Paulo Clemente

; Malbergier, André

; Spedo, Mariana Abrahão

; Kamitsuji, Carla Satie

; Faria, Elizabeth de

; Moreira, Moacyr Vergara de Godoy

; Kaufman, Arthur

; Abdo, Carmita

; Scanavino, Marco de Tubino

; Lancman, Selma

; Tavares, Hermano

; Polanczyk, Guilherme

; Brunoni, André R.

; Forlenza, Orestes V.

; Barros-Filho, Tarcísio Eloy Pessoa de

Clinics

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2021, Volume 76 elocation e2631

Resumo: En | Texto: En | PDF: En

OBJECTIVE: In 2020, the COVID-19 pandemic brought a work and stress overload to healthcare workers, increasing their vulnerability to mental health impairments. In response, the authors created the COMVC-19 program. The program offered preventive actions and mental health treatment for the 22,000 workers of The Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). This paper aims to describe its implementation and share what we have learned from this experience. METHODS: Workers were able to easily access the program through a 24/7 hotline. Additionally, a mobile phone app that screened for signs and symptoms of emotional distress and offered psychoeducation and/or referral to treatment was made available. Data from both these sources as well as any subsequent psychiatric evaluations were collected. RESULTS: The first 20 weeks of our project revealed that most participants were female, and part of the nursing staff working directly with COVID-19 patients. The most frequently reported symptoms were: anxiety, depression and sleep disturbances. The most common diagnoses were Adjustment, Anxiety, and Mood disorders. CONCLUSIONS: Implementing a mental health program in a multimodal intervention was feasible in a major quaternary public hospital. Our data also suggests that preventive actions should primarily be aimed at anxiety and depression symptoms, with a particular focus on the nursing staff.

https://doi.org/10.6061/clinics/2021/e2631

11.

Cognitive impairment: an (in)dependent risk factor for mortality in older men?
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Loureiro, Júlia C.

; Pais, Marcos V.

; Forlenza, Orestes V.

Brazilian Journal of Psychiatry

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Dez 2020, Volume 42 Nº 6 Páginas 577 - 578

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1590/1516-4446-2020-0017 296 downloads

12.

Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges
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Pais, Marcos

; Martinez, Luana

; Ribeiro, Octávio

; Loureiro, Júlia

; Fernandez, Romel

; Valiengo, Leandro

; Canineu, Paulo

; Stella, Florindo

; Talib, Leda

; Radanovic, Marcia

; Forlenza, Orestes V.

Brazilian Journal of Psychiatry

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Ago 2020, Volume 42 Nº 4 Páginas 431 - 441

Resumo: En | Texto: En | PDF: En

The prevalence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the “amyloid cascade” and the “continuum of AD,” discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.

https://doi.org/10.1590/1516-4446-2019-0735 6349 downloads

13.

Correlation between CSF biomarkers of Alzheimer’s disease and global cognition in a psychogeriatric clinic cohort
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Radanovic, Márcia

; Oshiro, Carlos A.

; Freitas, Thiago Q.

; Talib, Leda L.

; Forlenza, Orestes V.

Brazilian Journal of Psychiatry

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Dez 2019, Volume 41 Nº 6 Páginas 479 - 484

Resumo: En | Texto: En | PDF: En

Objective: The relationship between biomarkers of amyloid-beta aggregation (Aβ1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. Methods: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer’s disease (AD), and 26 with other dementias (OD). Results: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aβ1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aβ1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). Conclusion: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.

https://doi.org/10.1590/1516-4446-2018-0296 954 downloads

14.

Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer’s disease patients
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JOAQUIM, HELENA P. G.

; COSTA, ALANA C.

; FORLENZA, ORESTES V.

; GATTAZ, WAGNER F.

; TALIB, LEDA L.

Archives of Clinical Psychiatry (São Paulo)

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Out 2019, Volume 46 Nº 5 Páginas 120 - 124

Resumo: En | Texto: En | PDF: En

Abstract Background Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer’s disease (AD). Objective The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.

https://doi.org/10.1590/0101-60830000000209 768 downloads

15.

Topography of 11C-Pittsburgh compound B uptake in Alzheimer’s disease: a voxel-based investigation of cortical and white matter regions
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Faria, Daniele de P.

; Duran, Fabio L.

; Squarzoni, Paula

; Coutinho, Artur M.

; Garcez, Alexandre T.

; Santos, Pedro P.

; Brucki, Sonia M.

; de Oliveira, Maira O.

; Trés, Eduardo S.

; Forlenza, Orestes V.

; Nitrini, Ricardo

; Buchpiguel, Carlos A.

; Busatto Filho, Geraldo

Brazilian Journal of Psychiatry

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Abr 2019, Volume 41 Nº 2 Páginas 101 - 111

Resumo: En | Texto: En | PDF: En

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

https://doi.org/10.1590/1516-4446-2017-0002 1643 downloads

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