WILSON JACOB FILHO

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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

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  • article 27 Citação(ões) na Scopus
    Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis
    (2018) NASCIMENTO, C.; ALHO, A. T. Di Lorenzo; AMARAL, C. Bazan Conceicao; LEITE, R. E. P.; NITRINI, R.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; HOKKANEN, S. R. K.; HUNTER, S.; KEAGE, H.; KOVACS, G. G.; GRINBERG, L. T.; SUEMOTO, C. K.
    ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
  • article 31 Citação(ões) na Scopus
    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, Beny
    Background: 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.
  • article 5 Citação(ões) na Scopus
    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 Junqueira
    Objective: 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.
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  • article 28 Citação(ões) na Scopus
    Comparison of 3 Frailty Instruments in a Geriatric Acute Care Setting in a Low-Middle Income Country
    (2018) LIN, Sumika Mori; ALIBERTI, Marlon Juliano Romero; FORTES-FILHO, Sileno de Queiroz; MELO, Juliana de Araujo; APRAHAMIAN, Ivan; SUEMOTO, Claudia Kimie; JACOB FILHO, Wilson
    Objective: Comparison of frailty instruments in low-middle income countries, where the prevalence of frailty may be higher, is scarce. In addition, less complex diagnostic tools for frailty are important in these settings, especially in acutely ill patients, because of limited time and economic resources. We aimed to compare the performance of 3 frailty instruments for predicting adverse outcomes after 1 year of followup in older adults with an acute event or a chronic decompensated disease. Design: Prospective cohort study. Setting: Geriatric day hospital (GDH) specializing in acute care. Participants: A total of 534 patients (mean age 79.6 +/- 8.4 years, 63% female, 64% white) admitted to the GDH. Measurements: Frailty was assessed using the Cardiovascular Health Study (CHS) criteria, the Study of Osteoporotic Fracture (SOF) criteria, and the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) questionnaire. Monthly phone contacts were performed over the course of the first year to detect the following outcomes: incident disability, hospitalization, fall, and death. Multivariable Cox proportional hazard regression models were performed to evaluate the association of the outcomes with frailty as defined by the 3 instruments. In addition, we compared the accuracy of these instruments for predicting the outcomes. Results: Prevalence of frailty ranged from 37% (using FRAIL) to 51% (using CHS). After 1 year of follow-up, disability occurred in 33% of the sample, hospitalization in 40%, fall in 44%, and death in 16%. Frailty, as defined by the 3 instruments was associated with all outcomes, whereas prefrailty was associated with disability, using the SOF and FRAIL instruments, and with hospitalization using the CHS and SOF instruments. The accuracy of frailty to predict different outcomes was poor to moderate with area under the curve varying from 0.57 (for fall, with frailty defined by SOF and FRAIL) to 0.69 (for disability, with frailty defined by CHS). Conclusions: In acutely ill patients from a low-middle income country GDH acute care unit, the CHS, SOF, and FRAIL instruments showed similar performance in predicting adverse outcomes. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
  • article 20 Citação(ões) na Scopus
    Targeted Geriatric Assessment for Fast-Paced Healthcare Settings: Development, Validity, and Reliability
    (2018) ALIBERTI, Marlon J. R.; APOLINARIO, Daniel; SUEMOTO, Claudia K.; MELO, Juliana A.; FORTES-FILHO, Sileno Q.; SARAIVA, Marcos D.; TRINDADE, Carolina B.; COVINSKY, Kenneth E.; JACOB-FILHO, Wilson
    ObjectivesTo develop and examine the validity and reliability of a targeted geriatric assessment (TaGA) for busy healthcare settings. DesignThe TaGA was developed through the consensus of experts (Delphi technique), and we investigated its construct validity and reliability in a cross-sectional study. SettingGeriatric day hospital specializing in acute care in Brazil. ParticipantsOlder adults (N = 534) aged 79.5 8.4, 63% female, consecutively admitted to the geriatric day hospital. MeasurementsThe Frailty Index (FI), Physical Frailty Phenotype, and Identification of Seniors at Risk (ISAR) were used to explore the TaGA's validity. External scales were used to investigate the validity of each matched TaGA domain. The interrater reliability and time to complete the instrument were tested in a 53-person subsample. ResultsIn 3 rounds of opinion, experts achieved consensus that the TaGA should include 10 domains (social support, recent hospital admissions, falls, number of medications, basic activities of daily living, cognitive performance, self-rated health, depressive symptoms, nutritional status, gait speed). They arrived at sufficient agreement on specific tools to assess each domain. A single numerical score from 0 to 1 expressed the cumulative deficits across the 10 domains. The TaGA score was highly correlated with the FI (Spearman coefficient = 0.79, 95% confidence interval (CI)=0.76-0.82) and discriminated between frail and nonfrail individuals better than the ISAR (area under the receiver operating characteristic curve 0.84 vs 0.72; P < .001). The TaGA score also had excellent interrater reliability (intraclass correlation coefficient = 0.92, 95% CI=0.87-0.95). Mean TaGA administration time was 9.5 +/- 2.2 minutes. ConclusionThe study presents evidence supporting the TaGA's validity and reliability. This instrument may be a practical and efficient approach to screening geriatric syndromes in fast-paced healthcare settings. Future research should investigate its predictive value and effect on care.
  • article 47 Citação(ões) na Scopus
    Feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus (TM) for frail older adults: A randomized feasibility clinical trial
    (2018) GOMES, Gisele Cristine Vieira; SIMOES, Maria do Socorro; LIN, Sumika Mori; BACHA, Jessica Maria Ribeiro; VIVEIRO, Larissa Alamino Pereira; VARISE, Eliana Maria; CARVAS JUNIOR, Nelson; LANGE, Belinda; JACOB FILHO, Wilson; POMPEU, Jose Eduardo
    Background: Recently, interactive video games (IVGs) have been used as a health-care intervention that provides both exercise and cognitive stimulation. Several studies have shown that IVGs can improve postural control, gait, cognition, and functional independence in elderly people and patients with neurological disease. However, there is a lack of evidence about the effects of IVGs on frail and pre-frail elderly people. The aim of this study was to evaluate the feasibility, safety, and acceptability of playing Nintendo Wii Fit Plus (TM) (NWFP) interactive video games, and the functional outcomes (postural control, gait, cognition, mood, and fear of falling) in frail and pre-frail older adults. Methods: This study is a randomized controlled, parallel-group, feasibility trial. Participants were frail and pre-frail older adults randomly assigned to the experimental group (EG, n = 15) or control group (CG, n = 15). Participants in the EG performed 14 training sessions, lasting 50 min each, twice a week. In each training session, participants played five of 10 selected games, with two attempts at each game. Participants in the CG received general advice regarding the importance of physical activity. All participants were assessed on three occasions by a blinded physical therapist: before and after intervention, and 30 days after the end of the intervention (follow-up). We assessed the feasibility (score of participants in the games), acceptability (game satisfaction questionnaire), safety (adverse events during training sessions), and functional outcomes: (1) postural control (Mini-BESTest); (2) gait (Functional Gait Assessment); (3) cognition (Montreal Cognitive Assessment); (4) mood (GDS-15); and (5) fear of falling (FES-I). Results: Participants in the EG improved their scores in all 10 games, reported that they understood and enjoyed the tasks of the games, and presented few adverse events during the practice. There was a significant improvement in the Mini-BESTest and Functional Gait Assessment in the EG when compared with the CG (p < 0.05). Conclusion: The use of NWFP was feasible, acceptable, and safe for frail older adults and improved their postural control and gait. There were no effects on cognition, mood, or fear of falling. This trial was registered in the Brazilian Registry of Clinical Trials (RBR-823rst) on 11 June 2016.
  • article 8 Citação(ões) na Scopus
    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, Beny
    ObjectiveWe 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.
  • article 62 Citação(ões) na Scopus
    Persistent pain is a risk factor for frailty: a systematic review and meta-analysis from prospective longitudinal studies
    (2018) SARAIVA, Marcos Daniel; SUZUKI, Gisele Sayuri; LIN, Sumika Mori; ANDRADE, Daniel Ciampi de; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie
    Background: pain is prevalent in frail older adults; however, the association of pain and frailty has not been evaluated yet by a systematic assessment of prospective longitudinal studies. Objective: we aimed to assess the association of persistent pain as a risk factor for frailty incidence, using data from longitudinal studies in a systematic review and meta-analysis. Methods: publications were identified using a systematic search on PubMed, Embase, Cochrane Library and clinicaltrials. gov databases from inception to October 2017. Since heterogeneity across studies was high, we used random-effects metaanalysis to calculate the pooled relative risk for the association between persistent pain and the incidence of frailty. We investigated sources of heterogeneity among studies using meta-regression and stratified analyses. Results: we included five prospective longitudinal studies with 13,120 participants (46% women, mean age from 59 to 85 years old). Participants with persistent pain at baseline had twice the risk of developing frailty during the follow-up (pooled RR = 2.22, 95% CI = 1.14-4.29). No variables were related to study heterogeneity in sensitivity analyses. Conclusion: persistent pain was a risk factor for the development of frailty in a meta-analysis of longitudinal studies. Better understanding of the association between pain and frailty with proper evaluation of potential confounders could allow the development of targeted interventions.
  • article 126 Citação(ões) na Scopus
    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.