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
18 resultados
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bookPart Decisão terapêutica baseada em comorbidades e funcionalidade(2017) JACOB-FILHO, Wilson; JúNIOR, Luiz Antonio Gil- Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease(2017) EHRENBERG, A. J.; NGUY, A. K.; THEOFILAS, P.; DUNLOP, S.; SUEMOTO, C. K.; ALHO, A. T. Di Lorenzo; LEITE, R. P.; RODRIGUEZ, R. Diehl; MEJIA, M. B.; RUEB, U.; FARFEL, J. M.; FERRETTI-REBUSTINI, R. E. de Lucena; NASCIMENTO, C. F.; NITRINI, R.; PASQUALLUCCI, C. A.; JACOB-FILHO, W.; MILLER, B.; SEELEY, W. W.; HEINSEN, H.; GRINBERG, L. T.AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-m-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9x between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
conferenceObject THE DOWREGULATION EXPRESSION OF PROLINE OXIDASE GENE IMBALANCE GLUTAMATE IN BRAINS OF THE SUBJECTS WITH OBSESSIVE COMPULSIVE DISORDER A POST MORTEM STUDY(2017) OLIVEIRA, Katia de; LISBOA, Bianca Cristina Garcia; CARREIRA, Luzia Lima; GOUVEIA, Gisele Rodrigues; MORETTO, Ariane Cristine; NEVES, Ricardo de Caires; PASQUA-LUCCI, Carlos Augusto; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; LAFER, Beny; MIGUEL, Euripedes Constantino; SHAVITT, Roseli Gedanke; HOEXTER, Marcelo Queiroz; PEREIRA, Carlos Alberto de Bragranca; BRENTANI, Helena- Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery(2017) THEOFILAS, Panos; EHRENBERG, Alexander J.; DUNLOP, Sara; ALHO, Ana T. Di Lorenzo; NGUY, Austin; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; MEJIA, Maria B.; SUEMOTO, Claudia K.; FERRETTI-REBUSTINI, Renata Eloah De Lucena; POLICHISO, Livia; NASCIMENTO, Camila F.; SEELEY, William W.; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; RUEB, Udo; NEUHAUS, John; HEINSEN, Helmut; GRINBERG, Lea T.Introduction: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). Methods: The methods include unbiased stereologiCal analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. Results: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC. Discussion: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.
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- Association between delirium superimposed on dementia and mortality in hospitalized older adults: A prospective cohort study(2017) AVELINO-SILVA, Thiago J.; CAMPORA, Flavia; CURIATI, Jose A. E.; JACOB-FILHO, WilsonBackground Hospitalized older adults with preexisting dementia have increased risk of having delirium, but little is known regarding the effect of delirium superimposed on dementia (DSD) on the outcomes of these patients. Our aim was to investigate the association between DSD and hospital mortality and 12-mo mortality in hospitalized older adults. Methods and findings This was a prospective cohort study completed in the geriatric ward of a university hospital in Sao Paulo, Brazil. We included 1,409 hospitalizations of acutely ill patients aged 60 y and over from January 2009 to June 2015. Main variables and measures included dementia and dementia severity (Informant Questionnaire on Cognitive Decline in the Elderly, Clinical Dementia Rating) and delirium (Confusion Assessment Method). Primary outcomes were time to death in the hospital and time to death in 12 mo (for the discharged sample). Comprehensive geriatric assessment was performed at admission, and additional clinical data were documented upon death or discharge. Cases were categorized into four groups (no delirium or dementia, dementia alone, delirium alone, and DSD). The no delirium/dementia group was defined as the referent category for comparisons, and multivariate analyses were performed using Cox proportional hazards models adjusted for possible confounders (sociodemographic information, medical history and physical examination data, functional and nutritional status, polypharmacy, and laboratory covariates). Overall, 61% were women and 39% had dementia, with a mean age of 80 y. Dementia alone was observed in 13% of the cases, with delirium alone in 21% and DSD in 26% of the cases. In-hospital mortality was 8% for patients without delirium or dementia, 12% for patients with dementia alone, 29% for patients with delirium alone, and 32% for DSD patients (Pearson Chi-square = 112, p < 0.001). DSD and delirium alone were independently associated with in-hospital mortality, with respective hazard ratios (HRs) of 2.14 (95% CI = 1.33-3.45, p = 0.002) and 2.72 (95% CI = 1.77-4.18, p < 0.001). Dementia alone did not have a significant statistical association with in-hospital mortality (HR = 1.69, 95% CI = 0.72-2.30, p = 0.385). Finally, while 24% of the patients died after discharge, 12-mo mortality was not associated with dementia or delirium in any of the diagnostic groups (DSD: HR = 1.15, 95% CI = 0.79-1.68, p = 0.463; delirium alone: HR = 1.05, 95% CI = 0.71-1.54, p = 0.810; dementia alone: HR = 1.19, 95% CI = 0.79-1.78, p = 0.399). Limitations to this study include not exploring the effects of the duration and severity of delirium on the outcomes. Conclusions DSD and delirium alone were independently associated with a worse prognosis in hospitalized older adults. Health care professionals should recognize the importance of delirium as a predictor of hospital mortality regardless of the coexistence with dementia.
- Screening for Frailty With the FRAIL Scale: A Comparison With the Phenotype Criteria(2017) APRAHAMIAN, Ivan; CEZAR, Natalia Oiring de Castro; IZBICKI, Rafael; LIN, Sumika Mori; PAULO, Debora Lee Vianna; FATTORI, Andre; BIELLA, Marina Maria; JACOB FILHO, Wilson; YASSUDA, Monica SanchesBackground: Reliable and valid frailty screening instruments are lacking. The aim of the present study was to compare the diagnostic properties of the FRAIL-BR with Fried's frailty phenotype (CHS), which has not been done. Methods: Cross-sectional observational study of 124 older adults aged 60 or older from 2 university-based geriatric outpatient units in the state of Sao Paulo, Brazil. In ROC analyses, we evaluated different cutoff points and AUC areas of the FRAIL-BR compared with the CHS criteria. Also, components of both diagnostic strategies had head-to-head comparisons whenever possible. Results: The sample was composed mostly of overweight (mean BMI = 29.5 kg/m(2)) women (83%) with mean age of 78.6 (+/- 7.1) years. Prevalence of frailty varied according to the FRAIL-BR (23.3%) and the CHS criteria (14.5%) (P = .04). A cutoff of 3 points in the FRAIL-BR presented a sensitivity of 28% and specificity of 90% (P = .049). A cutoff of 2 points resulted in a sensitivity of 54% and specificity of 73% (P = .01). Comparisons of 4 FRAIL-BR items (ie, weight loss, aerobic capacity, fatigue, and physical resistance) to the respective CHS components showed an independent diagnostic property of all measures, with the exception for weight loss. Conclusion: The FRAIL scale can be used as a screening instrument for frailty (time and cost-effective). (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
conferenceObject Increased levels of TDP-43 protein in postmortem brain tissue of bipolar disorder subjects(2017) NASCIMENTO, C.; KIM, H. Kyunghee; OLIVEIRA, K. Cristina de; MORETTO, A. C.; BRENTANI, H. P.; ANDREAZZA, A.; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. E. D. L.; SUEMOTO, C. Kimie; PASQUALUCCI, C. Augusto; NITRINI, R.; FARFEL, J. M.; JACOB-FILHO, W.; NUNES, P. Villela; LAFER, B.- Predictors of Enteral Tube Feeding in Hospitalized Older Adults(2017) CRENITTE, Milton Roberto Furst; AVELINO-SILVA, Thiago Junqueira; APOLINARIO, Daniel; CURIATI, Jose Antonio Esper; CAMPORA, Flavia; JACOB-FILHO, WilsonBackground: Despite general recognition that enteral tube feeding (ETF) is frequently employed in long-term care facilities and patients with dementia, remarkably little research has determined which factors are associated with its use in acutely ill older adults. In this study, we aimed to investigate determinants of ETF introduction in hospitalized older adults. Methods: We examined a retrospective cohort of acutely ill patients, aged 60 years and older, admitted to a university hospital's geriatric ward from 2014-2015, in SAo Paulo, Brazil. The main outcome was the introduction of ETF during hospitalization. Predictors of interest included age, sex, referring unit, comorbidity burden, functional status, malnutrition, depression, dementia severity, and delirium. Multivariate analysis was performed using backward stepwise logistic regression. Results: A total of 214 cases were included. Mean age was 81 years, and 63% were women. Malnutrition was detected in 47% of the cases, dementia in 46%, and delirium in 36%. ETF was initiated in 44 (21%) admissions. Independent predictors of ETF were delirium (odds ratio [OR], 4.83; 95% CI, 2.12-11.01; P < .001) and total functional dependency (OR, 8.95; 95% CI, 2.87-27.88; P < .001). Malnutrition was not independently associated with ETF. Conclusion: One in five acutely ill older adults used ETF while hospitalized. Delirium and functional dependency were independent predictors of its introduction. Risks and benefits of enteral nutrition in this particular context need to be further explored.
- Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study(2017) SUEMOTO, Claudia K.; FERRETTI-REBUSTINI, Renata E. L.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; SOTERIO, Luciana; BRUCKI, Sonia M. D.; SPERA, Raphael R.; CIPPICIANI, Tarcila M.; FARFEL, Jose M.; CHIAVEGATTO FILHO, Alexandre; NASLAYSKY, Michel Satya; ZATZ, Mayana; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; NITRINI, Ricardo; GRINBERG, Lea T.Background Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. Methods and findings In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (beta = 1.33, 95% CI 1.20-1.46), IQCODE (beta = 0.14, 95% CI 0.13-0.16), and NPI (beta = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. Conclusions NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.