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
41 resultados
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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- 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.
- Crash Risk Predictors in Older Drivers: A Cross-Sectional Study Based on a Driving Simulator and Machine Learning Algorithms(2023) SILVA, V. C.; DIAS, A. S.; GREVE, J. M. D.; DAVIS, C. L.; SOARES, A. L. D. S.; BRECH, G. C.; AYAMA, S.; JACOB-FILHO, W.; BUSSE, A. L.; BIASE, M. E. M. de; CANONICA, A. C.; ALONSO, A. C.The ability to drive depends on the motor, visual, and cognitive functions, which are necessary to integrate information and respond appropriately to different situations that occur in traffic. The study aimed to evaluate older drivers in a driving simulator and identify motor, cognitive and visual variables that interfere with safe driving through a cluster analysis, and identify the main predictors of traffic crashes. We analyzed the data of older drivers (n = 100, mean age of 72.5 ± 5.7 years) recruited in a hospital in São Paulo, Brazil. The assessments were divided into three domains: motor, visual, and cognitive. The K-Means algorithm was used to identify clusters of individuals with similar characteristics that may be associated with the risk of a traffic crash. The Random Forest algorithm was used to predict road crash in older drivers and identify the predictors (main risk factors) related to the outcome (number of crashes). The analysis identified two clusters, one with 59 participants and another with 41 drivers. There were no differences in the mean of crashes (1.7 vs. 1.8) and infractions (2.6 vs. 2.0) by cluster. However, the drivers allocated in Cluster 1, when compared to Cluster 2, had higher age, driving time, and braking time (p < 0.05). The random forest performed well (r = 0.98, R2 = 0.81) in predicting road crash. Advanced age and the functional reach test were the factors representing the highest risk of road crash. There were no differences in the number of crashes and infractions per cluster. However, the Random Forest model performed well in predicting the number of crashes.
- Muscle strength, postural balance, and cognition are associated with braking time during driving in older adults(2016) ALONSO, Angelica C.; PETERSON, Mark D.; BUSSE, Alexandre L.; JACOB-FILHO, Wilson; BORGES, Mauricio T. A.; SERRA, Marcos M.; LUNA, Natalia M. S.; MARCHETTI, Paulo H.; GREVE, Julia M. D. A.Background: Despite the well-known declines in driving performance with advancing age, there is little understanding of the specific factors that predict changes in key determinants such as braking time. Objectives: The aims of this study were to determine the extent to which age, muscle strength, cognition and postural balance are associated with braking performance in middle-aged and older adults. Methods: Male and female middle-aged adults (n = 62, age = 39.3 +/- 7.1 years) and older adults (n = 102, age = 70.4 +/- 5.8 years) were evaluated for braking performance, as well as in several motor and cognitive performance tasks. The motor evaluation included isokinetic ankle plantar flexor muscle strength, handgrip strength, and postural balance with and without a cognitive task. The cognitive assessment included the Mini Mental State Examination. Braking performance was measured using a driving simulator. Results: Older adults exhibited 17% slower braking time, lower strength, and poorer performance in the postural balance (p < 0.001). For both older and middle-aged adults, significant correlates of braking time included performance in the postural balance tests, muscle strength, and cognitive function. However, after full model adjustment, only postural balance and cognitive function were significantly associated. Conclusion: Muscle strength, postural balance, and cognition are associated with braking time, and may affect the safety of and driving performance in older adults. These findings may help to inform specific targeted interventions that could preserve driving performance during aging.
- LEARNING TO READ IN OLDER AGE IMPROVES COGNITIVE PERFORMANCE: FINDINGS FROM A PROSPECTIVE OBSERVATIONAL STUDY(2014) SILVA, Eduardo Marques da; APOLINARIO, Daniel; MAGALDI, Regina Miksian; BENNETT, David A.; NITRINI, Ricardo; JACOB FILHO, Wilson; FARFEL, Jose Marcelo
- Direct Measurements of Abdominal Visceral Fat and Cognitive Impairment in Late Life: Findings From an Autopsy Study(2019) NISHIZAWA, Aline; CUELHO, Anderson; FARIAS-ITAO, Daniela S. de; CAMPOS, Fernanda M.; LEITE, Renata E. P.; FERRETTI-REBUSTINI, Renata E. L.; GRINBERG, Lea T.; NITRINI, Ricardo; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.; SUEMOTO, Claudia K.Background: The relationship between cognitive impairment and abdominal visceral is controversial. Moreover, all studies so far used imaging studies to evaluate visceral fat and this association has not been described yet using autopsy material, which allows the direct quantification of abdominal fat. We aimed to investigate the association between direct measurements of abdominal visceral fat and cognitive impairment in an autopsy study. Methods: In this cross-sectional study, we collected information on sociodemographics, cardiovascular risk factors, and cognitive status from subjects aged 50 or older at time of death in a general autopsy service in Brazil. Abdominal visceral fat was obtained in natura by the dissection of perirenal, mesenteric, omental, and mesocolon fat. The associations of total abdominal visceral fat with cognitive impairment [clinical dementia rating (CDR) score >= 0.5] and CDR-sum of boxes (CDR-SB) were evaluated using logistic regression and negative binomial regression models, respectively. All analyses were adjusted for height, age, sex, education, hypertension, diabetes mellitus, stroke, smoking, alcohol use, and physical inactivity. In addition, we compared the discrimination of visceral fat, body mass index (BMI), and waist circumference (WC) measurements in predicting cognitive impairment. Results: We evaluated 234 participants (mean age = 71.2 +/- 12.9 years old, 59% male). Abdominal visceral fat was inversely associated with cognitive impairment (OR = 0.46, CI = 0.30; 0.70, p < 0.0001) and with CDR-SB scores (beta = 0.85, 95% CI = 1.28; 0.43, p < 0.0001). When we compared the area under the ROC curve (AUC), visceral fat (AUC = 0.754), BMI (AUC = 0.729), and WC (AUC = 0.720) showed similar discrimination in predicting cognitive impairment (p = 0.38). Conclusion: In an autopsy study, larger amount of directly measured abdominal visceral fat was associated with lower odds of cognitive impairment in older adults.
- 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, WilsonObjectivesTo 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.
- Apolipoprotein E genotypes were not associated with intracranial atherosclerosis: a population-based autopsy study br(2023) PARADELA, Regina Silva; FARIAS-ITAO, Daniela Souza; LEITE, Renata E. P.; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; NASLAVSKY, Michel Satya; ZATZ, Mayana; NITRINI, Ricardo; JACOB-FILHO, Wilson; SUEMOTO, Claudia KimieBackground: Apolipoprotein E gene (APOE) 64 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study.Methods: We measured the stenosis in the 12 arteries of the Circle of Willis using postmortem morphometric measurements. The APOE polymorphism was determined by real-time polymerase chain reaction. We assessed the association between APOE polymorphism and IAD using regression models adjusted for sociodemographic and clinical variables. We also verified the modifier effect of age, sex, and race on this association. We stratified the analysis by age group to investigate the possibility of attrition bias.Results: In 400 participants (mean age = 73.2 +/- 12.3 years old, 51% female, and 64% White), IAD was evaluated in 4,504 artery segments. APOE- 64 was not associated with IAD nor with the number of artery stenosis compared to non-APOE- 64 carriers. Sociodemographic variables did not modify this relationship. Among participants older than 70 years, there was a trend towards an association between APOE allele 64 and a lower stenosis index in the middle cerebral artery, suggesting attrition bias related to the APOE- 64 effect on mortality.Conclusions: APOE alleles were not associated with IAD in this population-based autopsy study. Lower stenosis in older participants suggests the possibility of attrition bias.
- Similar Microglial Cell Densities across Brain Structures and Mammalian Species: Implications for Brain Tissue Function(2020) SANTOS, Sandra E. Dos; MEDEIROS, Marcelle; PORFIRIO, Jairo; TAVARES, William; PESSOA, Leila; GRINBERG, Lea; LEITE, Renata E. P.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB FILHO, Wilson; NOCTOR, Stephen; SHERWOOD, Chet C.; KAAS, Jon H.; MANGER, Paul R.; HERCULANO-HOUZEL, SuzanaMicroglial cells play essential volume-related actions in the brain that contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Microglia can thus be expected to have similar cell sizes and even distribution both across brain structures and across species with different brain sizes. To test this hypothesis, we determined microglial cell densities (the inverse of cell size) using immunocytochemistry to Ibal in samples of free cell nuclei prepared with the isotropic fractionator from brain structures of 33 mammalian species belonging to males and females of five different clades. We found that microglial cells constitute similar to 7% of non-neuronal cells in different brain structures as well as in the whole brain of all mammalian species examined. Further, they vary little in cell density compared with neuronal cell densities within the cerebral cortex, across brain structures, across species within the same Glade, and across mammalian clades. As a consequence, we find that one microglial cell services as few as one and as many as 100 neurons in different brain regions and species, depending on the local neuronal density. We thus conclude that the addition of microglial cells to mammalian brains is governed by mechanisms that constrain the size of these cells and have remained conserved over 200 million years of mammalian evolution. We discuss the probable consequences of such constrained size for brain function in health and disease.
- Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?(2019) GODOY, Maria Dantas Costa Lima; FORNAZIERI, Marco Aurelio; DOTY, Richard L.; PINNA, Fabio de Rezende; FARFEL, Jose Marcelo; SANTOS, Glaucia Bento dos; MOLINA, Mariana; FERRETTI-REBUSTINI, Renata E. L.; LEITE, Renata E. P.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASCRALUCCI, Carlos A. G.; VOEGELS, Richard Louis; NITRINI, Ricardo; JACOB FILHO, WilsonObjectives: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with ""silent"" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.