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
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- Very low levels of education and cognitive reserve A clinicopathologic study(2013) FARFEL, Jose Marcelo; NITRINI, Ricardo; SUEMOTO, Claudia Kimie; GRINBERG, Lea Tenenholz; FERRETTI, Renata Eloah Lucena; LEITE, Renata Elaine Paraizo; TAMPELLINI, Edilaine; LIMA, Luzia; FARIAS, Daniela Souza; NEVES, Ricardo Caires; RODRIGUEZ, Roberta Diehl; MENEZES, Paulo Rossi; FREGNI, Felipe; BENNETT, David A.; PASQUALUCCI, Carlos Augusto; JACOB FILHO, WilsonObjective: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. Methods: In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition. Results: Mean education was 3.9 +/- 3.5 years. Formal education was associated with a lower CDR sum of boxes (beta = -0.197; 95% confidence interval -0.343, -0.052; p = 0.008), after adjustment for sociodemographic variables and neuropathologic indices. Furthermore, education modified the relationship of lacunar infarcts with cognitive abilities (p = 0.04). Conclusions: Even a few years of formal education contributes to cognitive reserve.
article 48 Citação(ões) na Scopus Relation of genomic variants for Alzheimer disease dementia to common neuropathologies(2016) FARFEL, Jose M.; YU, Lei; BUCHMAN, Aron S.; SCHNEIDER, Julie A.; JAGER, Philip L. De; BENNETT, David A.Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in largescale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 X 10(-8)) for pathologic AD for all variants. Results: APOE epsilon 4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 X 10(-13)), while epsilon 2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 X 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies.- APOE epsilon 2 epsilon 4 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults(2018) OVEISGHARAN, Shahram; BUCHMAN, Aron S.; YU, Lei; FARFEL, Jose; HACHINSKI, Vladimir; GAITERI, Chris; JAGER, Philip L. De; SCHNEIDER, Julie A.; BENNETT, David A.Objective To examine the association of the APOE epsilon 2 epsilon 4 genotype with incident Alzheimer disease (AD), mild cognitive impairment (MCI), cognitive decline, and AD pathology in older adults. Methods We used data from 2,151 older adults of European ancestry who were free of dementia at baseline and underwent structured annual clinical evaluation in a longitudinal study for incident AD and MCI, and cognitive decline. Postmortem examination in decedents documented pathologic AD and quantified ss-amyloid and neurofibrillary tangles. Participants were stratified into 4 groups based on APOE genotyping: epsilon 2 epsilon 4, epsilon 4 (epsilon 4 epsilon 4, epsilon 4 epsilon 3), epsilon 2 (epsilon 2 epsilon 2, epsilon 2 epsilon 3), with epsilon 3 epsilon 3 carriers serving as the reference group. We used Cox proportional hazards models to examine the association of APOE genotype with incident AD and MCI. Linear mixed-effect models were used to examine the association with cognitive decline. Logistic and linear regression models were used to examine AD pathology. All the models controlled for age, sex, and education. Results Of the 2,151 participants included in this study, epsilon 2 epsilon 4 accounted for 2.1%, epsilon 3/4 and 4/4 21.8%, epsilon 2/3 and 2/2 14.0%, and epsilon 3 epsilon 3 62.1%. We did not observe a difference in the risk of AD for epsilon 2 epsilon 4 compared to epsilon 3 epsilon 3. In cases without cognitive impairment at baseline, epsilon 2 epsilon 4 carriers had an increased risk of incident MCI (hazard ratio 2.13, 95% confidence interval 1.34-3.39, p = 0.002) and a faster rate of cognitive decline (estimate -0.047, SE 0.018, p = 0.008) compared to epsilon 3 epsilon 3 carriers. In decedents (n = 1,100), epsilon 2 epsilon 4 showed a 3-fold increased odds of pathologic AD and a higher ss-amyloid load than epsilon 3 epsilon 3. Conclusion APOE epsilon 2 epsilon 4 genotype in older adults is associated with risk of MCI, cognitive decline, and a greater burden of AD pathology, especially ss-amyloid.