JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- 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.
- 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
- 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.
- Association of APOE with tau-tangle pathology with and without beta-amyloid(2016) FARFEL, Jose M.; YU, Lei; JAGER, Philip L. De; SCHNEIDER, Julie A.; BENNETT, David A.This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without beta-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting beta-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE epsilon 4 and epsilon 2 to PHF-tau-tangle density in persons with beta-amyloid relative to persons without beta-amyloid. We found an interaction between APOE epsilon 4 carriers and presence of beta-amyloid (beta = -0.968, p = 0.013) such that the association of APOE epsilon 4 with PHF-tau tangles was much stronger in brains with beta-amyloid. Stratified analysis shows that the association of APOE epsilon 4 with PHF-tau tangles was considerably stronger among those with beta-amyloid (beta = 0.757, p = 1.1 x 10(-15)) compared to those without beta-amyloid which was not significant (beta = -0.201, p = 0.424). Separately, APOE epsilon 2 was associated with fewer tangles in brains with beta-amyloid (beta = -0.425, p = 7.6 x 10(-4)) compared to those without beta-amyloid which was not significant (beta = -0.102, p = 0.506). Thus, the presence of APOE epsilon 4 and epsilon 2 alleles was not associated with PHF-tau tangles in the absence of beta-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of beta-amyloid may reflect a pathologic process distinct from Alzheimer's disease.
- Lower mitochondrial DNA content but not increased mutagenesis associates with decreased base excision repair activity in brains of AD subjects(2019) SOLTYS, Daniela T.; PEREIRA, Carolina P. M.; ROWIES, Fernanda T.; FARFEL, Jose M.; GRINBERG, Lea T.; SUEMOTO, Claudia K.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; ERICSON, Nolan G.; BIELAS, Jason H.; SOUZA-PINTO, Nadja C.Accumulation of oxidative mitochondrial DNA (mtDNA) damage and impaired base excision repair (BER) in brains have been associated with Alzheimer's disease (AD). However, it is still not clear how these affect mtDNA stability, as reported levels of mtDNA mutations in AD are conflicting. Thus, we investigated whether alterations in BER correlate with mtDNA instability in AD using postmortem brain samples from cognitively normal AD subjects and individuals who show neuropathological features of AD, but remained cognitively normal (high-pathology control). To date, no data on DNA repair and mtDNA stability are available for these individuals. BER activities, mtDNA mutations, and mtDNA copy number were measured in the nuclear and mitochondrial extracts. Significantly lower uracil DNA glycosylase activity was detected in nuclear and mitochondrial extracts from AD subjects, while apurinic/ apyrimidinic endonuclease activity was similar in all groups. Although mtDNA mutation frequency was similar in all groups, mtDNA copy number was significantly decreased in the temporal cortex of AD brains but not of high-pathology control subjects. Our results show that lower mitochondrial uracil DNA glycosylase activity does not result in increased mutagenesis, but rather in depletion of mtDNA in earlyaffected brain regions during AD development.
- Depression and cardiovascular risk factors: evidence from a large postmortem sample(2013) SUEMOTO, Claudia K.; DAMICO, Marcio V.; FERRETTI, Renata E. L.; GRINBERG, Lea T.; FARFEL, Jose Marcelo; LEITE, Renata E. P.; NITRINI, Ricardo; LAFER, Beny; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.Objectives We aimed to investigate the association of depression with cardiovascular risk factors and diseases (CVRFD) in a large population-based sample. Methods This cross-sectional study included 1012 deceased individuals greater than 50years of age from a general autopsy service located in SAo Paulo, Brazil. Demographics, socioeconomic profile, and CVRFD information were collected by caregivers from the deceased individuals from the Brain Bank of the Brazilian Aging Brain Study Group. Depression diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Mental Disorders was the main outcome. Results Depression was associated with female gender (odds ratio (OR)=1.86; 95% confidence interval (CI)=1.282.71, p=0.001), widowhood (OR=1.54; 95% CI=1.032.32, p=0.04), physical inactivity (OR=1.61; 95% CI=1.152.26, p=0.006), and smoking (OR=2.03; 95% CI=1.402.95, p<0.001) after multivariate logistic regression analysis. Other CVRFD were not associated with the presence of depression. Conclusions In our cross-sectional study, sedentary individuals and smokers showed a higher chance of depression during lifetime. Measures to control these common risk factors could decrease the incidence of depression.
- APOE and cerebral amyloid angiopathy in community-dwelling older persons(2015) YU, Lei; BOYLE, Patricia A.; NAG, Sukriti; LEURGANS, Sue; BUCHMAN, Aron S.; WILSON, Robert S.; ARVANITAKIS, Zoe; FARFEL, Jose M.; JAGER, Philip L. De; BENNETT, David A.; SCHNEIDER, Julie A.Both cerebral amyloid angiopathy and Alzheimer's disease pathology involve abnormal beta-amyloid processing. We aim to elucidate the relationship of the apolipoprotein E (APOE) genotypes with amyloid angiopathy in the presence of variable amounts of Alzheimer's pathology. Data came from 1062 autopsied subjects from 2 community-based studies of aging. Common neuropathologies including Alzheimer's disease and amyloid angiopathy were assessed using uniform methods. APOE was genotyped by sequencing the 2 polymorphisms in codons 112 and 158 of exon 4. We examined the associations of APOE with amyloid angiopathy using ordinal logistic regression analyses, controlling for demographics and subsequently Alzheimer's and other common pathologies. Moderate to severe amyloid angiopathy was identified in 35.2% (n = 374) of the subjects; 15.3% (n = 162) of the subjects were APOE epsilon 2 carriers; and 26.1% (n = 277) epsilon 4 carriers. Adjusting for demographics, the presence of epsilon 4 allele, but not epsilon 2, was associated with more severe amyloid angiopathy. After further adjustment for Alzheimer's pathology, both epsilon 2 (odds ratio 1.707, 95% confidence interval 1.236-2.358, p = 0.001) and epsilon 4 (odds ratio 2.284, 95% confidence interval 1.730-3.014, p < 0.001) were independently associated with amyloid angiopathy. The results were confirmed by path analysis. Furthermore, APOE epsilon 4 carriers, but not epsilon 2 carriers, were more likely to have capillary amyloid angiopathy. Accounting for capillary involvement did not alter the APOE associations with amyloid angiopathy. We conclude that both APOE epsilon 2 and epsilon 4 alleles are associated with more severe cerebral amyloid angiopathy, and the direct effect of epsilon 2 is masked by the allele's negative association with comorbid Alzheimer's pathology. APOE epsilon 4, but not epsilon 2, is associated with capillary amyloid angiopathy.
conferenceObject Prognostic assessment of hospitalized older adults with community-acquired pneumonia: a geriatric approach.(2015) MANDEL, S. A.; AVELINO-SILVA, T. J.; FARFEL, J. M.; JACOB-FILHO, W.- Factors associated with morphometric brain changes in cognitively normal aging(2015) FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie; FARFEL, José Marcelo; LEITE, Renata Elaine Paraiso; GRINBERG, Lea Tenenholz; PASQUALUCCI, Carlos Augusto; NITRINI, RicardoOBJECTIVE: Cognitive impairment is associated with reductions in brain weight and volume. The factors related to morphometric brain changes in cognitively normal aging remain unknown. We aimed to identify which clinical factors are associated with morphometric brain changes in cognitively normal aging. METHODS: A cross-sectional study of 414 subjects, ≥50 years old submitted to clinical assessment and brain autopsy, after informed consent, was carried out at the São Paulo Autopsy Service, Brazil. Data on cognitive and functional evaluations were collected through structured interview applied to the next-of-kin. Brain weight (g) and volume (mL) measurements were obtained and adjusted for head circumference (cm). Associations between brain weight/volume and related factors were obtained through univariate and multivariate analysis. RESULTS: Participants were predominantly male (60.4%), Caucasian (69%), with mean age of 67.1 ± 10.9 years. Mean brain weight was 1219.2 ± 140.9 g, and mean brain volume was 1217.1 ± 152.3 mL. Head circumference was independently associated with low brain weight (p<0.001) and volume (p<0.001). Total and adjusted brain weight and volume decreased in some conditions. Female gender (p<0.001), hypertension (p<0.009), coronary artery disease (p<0.013) and walking assistance (p<0.011) were associated with lower adjusted brain weight while schooling was associated with higher adjusted brain weight (p<0.003). Female gender (p<0.001), age (p<0.001) and hypertension (p<0.011) were associated with low adjusted brain volume. CONCLUSION: Morphometric brain changes occur despite the absence of cognitive impairment and were predominantly associated with age, female gender, mobility impairment and cardiovascular conditions. Schooling may be a protective factor.