WILSON JACOB FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
141 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 141
bookPart Decisão terapêutica baseada em comorbidades e funcionalidade(2017) JACOB-FILHO, Wilson; JúNIOR, Luiz Antonio Gil- 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.
- Clinical and laboratory characteristics associated with referral of hospitalized elderly to palliative care(2018) ARCANJO, Suelen Pereira; SAPORETTI, Luis Alberto; CURIATI, Jose Antonio Esper; JACOB-FILHO, Wilson; AVELINO-SILVA, Thiago JunqueiraObjective: To investigate clinical and laboratory characteristics associated with referral of acutely ill older adults to exclusive palliative care. Methods: A retrospective cohort study based on 572 admissions of acutely ill patients aged 60 years or over to a university hospital located in Sao Paulo, Brazil, from 2009 to 2013. The primary outcome was the clinical indication for exclusive palliative care. Comprehensive geriatric assessments were used to measure target predictors, such as sociodemographic, clinical, cognitive, functional and laboratory data. Stepwise logistic regression was used to identify independent predictors of palliative care. Results: Exclusive palliative care was indicated in 152 (27%) cases. In the palliative care group, in-hospital mortality and 12 month cumulative mortality amounted to 50% and 66%, respectively. Major conditions prompting referral to palliative care were advanced dementia (45%), cancer (38%), congestive heart failure (25%), stage IV and V renal dysfunction (24%), chronic obstructive pulmonary disease (8%) and cirrhosis (4%). Major complications observed in the palliative care group included delirium (p<0.001), infections (p<0.001) and pressure ulcers (p<0.001). Following multivariate analysis, male sex (OR=2.12; 95% CI: 1.32-3.40), cancer (OR=7.36; 95% CI: 4.26-13.03), advanced dementia (OR=12.6; 95% CI: 7.5-21.2), and albumin levels (OR=0.25; 95% CI: 0.17-0.38) were identified as independent predictors of referral to exclusive palliative care. Conclusion: Advanced dementia and cancer were the major clinical conditions associated with referral of hospitalized older adults to exclusive palliative care. High short-term mortality suggests prognosis should be better assessed and discussed with patients and families in primary care settings.
- Comprehensive geriatric assessment predicts mortality and adverse outcomes in hospitalized older adults(2014) AVELINO-SILVA, Thiago J.; FARFEL, Jose M.; CURIATI, Jose A. E.; AMARAL, Jose R. G.; CAMPORA, Flavia; JACOB-FILHO, WilsonBackground: Comprehensive Geriatric Assessment (CGA) provides detailed information on clinical, functional and cognitive aspects of older patients and is especially useful for assessing frail individuals. Although a large proportion of hospitalized older adults demonstrate a high level of complexity, CGA was not developed specifically for this setting. Our aim was to evaluate the application of a CGA model for the clinical characterization and prognostic prediction of hospitalized older adults. Methods: This was a prospective observational study including 746 patients aged 60 years and over who were admitted to a geriatric ward of a university hospital between January 2009 and December 2011, in Sao Paulo, Brazil. The proposed CGA was applied to evaluate all patients at admission. The primary outcome was in-hospital death, and the secondary outcomes were delirium, nosocomial infections, functional decline and length of stay. Multivariate binary logistic regression was performed to assess independent factors associated with these outcomes, including socio-demographic, clinical, functional, cognitive, and laboratory variables. Impairment in ten CGA components was particularly investigated: polypharmacy, activities of daily living (ADL) dependency, instrumental activities of daily living (IADL) dependency, depression, dementia, delirium, urinary incontinence, falls, malnutrition, and poor social support. Results: The studied patients were mostly women (67.4%), and the mean age was 80.5 +/- 7.9 years. Multivariate logistic regression analysis revealed the following independent factors associated with in-hospital death: IADL dependency (OR= 4.02; CI= 1.52-10.58; p= .005); ADL dependency (OR= 2.39; CI= 1.25-4.56; p= .008); malnutrition (OR= 2.80; CI= 1.63-4.83; p< .001); poor social support (OR= 5.42; CI= 2.93-11.36; p< .001); acute kidney injury (OR= 3.05; CI= 1.78-5.27; p< .001); and the presence of pressure ulcers (OR= 2.29; CI= 1.04-5.07; p= .041). ADL dependency was independently associated with both delirium incidence and nosocomial infections (respectively: OR= 3.78; CI= 2.30-6.20; p< .001 and OR= 2.30; CI= 1.49-3.49; p< .001). The number of impaired CGA components was also found to be associated with in-hospital death (p< .001), delirium incidence (p< .001) and nosocomial infections (p= .005). Additionally, IADL dependency, malnutrition and history of falls predicted longer hospitalizations. There were no significant changes in overall functional status during the hospital stay. Conclusions: CGA identified patients at higher risk of in-hospital death and adverse outcomes, of which those with functional dependence, malnutrition and poor social support were foremost.
- Education, but not occupation, is associated with cognitive impairment: The role of cognitive reserve in a sample from a low-to-middle-income country(2022) SUEMOTO, Claudia K.; BERTOLA, Laiss; GRINBERG, Lea T.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; SANTANA, Pedro H.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; NITRINI, RicardoIntroduction 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: beta= -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; >= 5 years: beta= -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.
conferenceObject Inflammatory factors (cytokines and cortisol) across different brain regions in bipolar disorder and their associations with neuropsychiatric symptoms: A post-mortem study(2020) NASCIMENTO, Camila; NUNES, Paula V.; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; BRENTANI, Helena P.; LAFER, Beny- The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex(2023) CASTRO-FONSECA, Emily; MORAIS, Viviane; SILVA, Camila G. da; WOLLNER, Juliana; FREITAS, Jaqueline; MELLO-NETO, Arthur F.; OLIVEIRA, Luiz E.; OLIVEIRA, Vilson C. de; LEITE, Renata E. P.; ALHO, Ana T.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; TOVAR-MOLL, Fernanda; LENT, RobertoThe human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has similar to 10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.
- Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis(2019) LISBOA, Bianca C. G.; OLIVEIRA, Katia C.; TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GOUVEIA, Gisele; LIMA, Luzia; SANTOS, Ana Cecilia Feio dos; JR, David Correa Martins; PUGA, Renato David; MORETTO, Ariane Cristine; PEREIRA, Carlos Alberto De Braganca; LAFER, Beny; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah De Lucena; FARFEL, Jose Marcelo; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo Queiroz; BRENTANI, HelenaObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
- Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer's Disease(2014) SILVA, Aderbal R. T.; SANTOS, Ana Cecilia Feio; FARFEL, Jose M.; GRINBERG, Lea T.; FERRETTI, Renata E. L.; CAMPOS, Antonio Hugo Jose Froes Marques; CUNHA, Isabela Werneck; BEGNAMI, Maria Dirlei; ROCHA, Rafael M.; CARRARO, Dirce M.; PEREIRA, Carlos Alberto de Braganca; JACOB-FILHO, Wilson; BRENTANI, HelenaAlzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p(27Kip1), phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) ""clinical-pathological AD"" (CP-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and clinical dementia (CDR >= 2, IQCODE >= 3.8); II) ""pathological AD"" (P-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE < 3.2); and III) ""normal aging"" (N) - subjects without neuropathological AD (Braak <= II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.
- Neuropathological correlates of neuropsychiatric symptoms in dementia(2023) GIBSON, Lucy L.; GRINBERG, Lea T.; FFYTCHE, Dominic; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; AARSLAND, Dag; SUEMOTO, Claudia K.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.