RENATA ELOAH DE LUCENA FERRETTI-REBUSTINI
Projetos de Pesquisa
Unidades Organizacionais
ENC, EE - Docente
LIM/66, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
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- Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample(2018) NUNES, Paula Villela; NASCIMENTO, Camila Fernandes; KIM, Helena Kyunghee; ANDREAZZA, Ana Cristina; BRENTANI, Helena Paula; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; GRINBERG, Lea Tenenholz; YONG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyBackground: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. Methods: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). Results: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (beta = - 0.106, 95%CI = - 0.204; - 0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. Limitations: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. Conclusions: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.
- Elaboração e validação da Escala Brasileira de Percepção sobre Eutanásia(2023) MURAKAMI, Beatriz Murata; FERRETTI-REBUSTINI, Renata Eloah de Lucena; AMENDOLA, Fernanda; ALMEIDA, Fabiane de AmorimAbstract This research elaborated an instrument to identify nurses’ perception on euthanasia and test its content validity, response process, internal structure and reliability evidences. A psychometric study was conducted through evaluation by a committee of judges, pre-test, and validation. The latter step included 821 nurses. Exploratory and confirmatory factor analyses were performed. A total of 55 items were elaborated based on a literature review. After review by judges and applying the suggested changes, all items showed agreement above 80% between evaluators. Exploratory and confirmatory factor analyses indicated a satisfactory fit of a two-dimensional model and good reliability indices (α=0.85; Ω=0.89). The 12-item scale showed good validity and reliability evidences, and can be used to measure nurses’ perception on euthanasia.
- Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study(2018) NUNES, Paula Villela; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; FARFEL, Jose Marcelo; OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; COSTA, Nicole Rezende da; NASCIMENTO, Camila Fernandes; SALMASI, Faraz; KIM, Helena Kyunghee; YOUNG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyObjectiveWe examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. MethodsIn this study, 1373 participants (787 male) aged 50years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. ResultsMean age at death was 68.611.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p<0.001), lower education (years; p<0.001), hypertension (p=0.001), diabetes (p=0.006), and female gender (p<0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (=-0.86, 95% CI=-26.50 to 24.77, p=0.95). ConclusionsIn this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education.
conferenceObject TRANSCRIPTOME STUDY IN STRIATUM OF OBSESSIVE COMPULSIVE DISORDERS (POSTMORTEM STUDY)(2017) LISBOA, Bianca; OLIVEIRA, Katia de; LIMA, Luzia Carreira; PUGA, Renato; RIBEIRO, Gustavo; TAHIRA, Ana; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; PAULS, David; SHAVITT, Roseli; HOEXTER, Marcelo; PEREIRA, Carlos Alberto de Braganca; BRENTANI, Helena- Content validity evidence of the Brazilian version of the Cognitive Symptom Checklist-Work-21(2023) ROCHA, Elaine Cristina Lopes da; SOUSA, Kayo Henrique Jardel Feitosa; LUCCHESI, Paola Alves de Oliveira; FARIA, Magda Guimaraes de Araujo; BALBINOTTI, Marcos Alencar Abaide; REBUSTINI, Flavio; FERRETTI-REBUSTINI, Renata Eloah de Lucena; GALLASCH, Cristiane HelenaObjective: to cross-culturally adapt and assess the content validity evidence of the Cognitive Symptom Checklist-Work-21 for the Brazilian context. Method: a psychometric study of cross-cultural adaptation, covering the stages of translation, reconciliation, back-translation, intercultural equivalence assessment and content validity evidence analysis, considering Content Validity Ratio parameters in breast cancer survivors. Results: the translations were equivalent to the original version. Colloquial expressions were modified, tense, verbal adjusted, and two items containing multiple commands were separated. The final version now contains 22 items, presenting semantic, conceptual, idiomatic and experimental equivalences. The pre-test indicated good understanding and ease in the response process. Conclusion: the final version was defined as ""Lista de verificacao de sintomas cognitivos relacionados ao trabalho -22 itens"", showing good linguistic equivalence and strong evidence of content validity in the Brazilian context.
- d Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study(2016) RODRIGUEZ, Roberta Diehl; SUEMOTO, Claudia Kimie; MOLINA, Mariana; NASCIMENTO, Camila Fernandes; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; FARFEL, Jose Marcelo; HEINSEN, Helmut; NITRINI, Ricardo; UEDA, Kenji; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; YAFFE, Kristine; GRINBERG, Lea TenenholzArgyrophilic grain disease (AGD) is a frequent late-onset, 4 repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects >50 years of age from Sao Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 +/- 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases.
- Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease(2018) EHRENBERG, Alexander J.; SUEMOTO, Claudia K.; RESENDE, Elisa de Paula Franca; PETERSEN, Cathrine; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; FERRETTI-REBUSTINI, Renata Eloah de Lucena; YOU, Michelle; OH, Jun; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; KRAMER, Joel H.; GATCHEL, Jennifer R.; GRINBERG, Lea T.Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-beta pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of Sao Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-beta burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-beta pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.
- Are the 50's, the transition decade, in choroid plexus aging?(2021) TAHIRA, Ana; MARQUES, Fernanda; LISBOA, Bianca; FELTRIN, Arthur; BARBOSA, Andre; OLIVEIRA, Katia Cristina de; PEREIRA, Carlos Alberto de Braganca; LEITE, Renata; GRINBERG, Lea; SUEMOTO, Claudia; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; BRENTANI, Helena; PALHA, Joana AlmeidaThe choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.
- Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder(2019) OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; HOEXTER, Marcelo Queiroz; BRENTANI, Helena; SUEMOTO, Claudia Kimie; NERY, Fabiano Goncalves; LIMA, Luzia Carreira; ALHO, Ana Tereza Di Lorenzo; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; LEITE, Renata Elaine Paraizo; MORETTO, Ariane Cristine; SILVA, Alexandre Valotta da; LAFER, Beny; MIGUEL, Euripedes Constantino; NITRINI, Ricardo; JACOB-FILHO, Wilson; HEINSEN, Helmut; PASQUALUCCI, Carlos AugustoNeurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.
- Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study(2016) NISHIZAWA, Aline; SUEMOTO, Claudia Kimie; FARIAS, Daniela Souza; CAMPOS, Fernanda Marinho; SILVA, Karen Cristina Souza da; CUELHO, Anderson; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; GRINBERG, Lea Tenenholz; FARFEL, Jose Marcelo; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos AugustoIntroduction: Adiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study. Methods and analysis: A sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and alpha=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80 degrees C for future studies. Ethics and dissemination: Ethical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal.