CARLOS AUGUSTO GONCALVES PASQUALUCCI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
11 resultados
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- Education, but not occupation, is associated with cognitive impairment: The role of cognitive reserve in a sample from a low-to-middle-income country(2022) SUEMOTO, Claudia K.; BERTOLA, Laiss; GRINBERG, Lea T.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; SANTANA, Pedro H.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; NITRINI, RicardoIntroduction Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. Methods In this cross-sectional study, cognitive function was assessed by the Clinical Dementia Rating sum of boxes (CDR-SOB). We investigated the association of occupation complexity and education with CDR-SOB using adjusted linear regression models for age, sex, and neuropathological lesions. Results In 1023 participants, 77% had < 5 years of education, and 56% unskilled occupations. Compared to the group without education, those with formal education had lower CDR-SOB (1-4 years: beta= -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; >= 5 years: beta= -1.42, 95% CI = -2.47; -0.38, P = .008). Occupation complexity and demands were unrelated to cognition. Discussion Education, but not occupation, was related to better cognitive abilities independent of the presence of neuropathological insults.
- Neuropsychiatric symptoms in community-dwelling older Brazilians with mild cognitive impairment and dementia(2022) SUEMOTO, Claudia Kimie; NUNES, Paula Villela; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; RODRIGUEZ, Roberta Diehl; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson
- Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study(2022) NASCIMENTO, Camila; V, Paula Nunes; KIM, Helena K.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; OLIVEIRA, Katia Cristina De; BRENTANI, Helena P.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; SUEMOTO, Claudia K.; LAFER, BenyBipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.
- Macrophage Polarization in the Perivascular Fat Was Associated With Coronary Atherosclerosis(2022) FARIAS-ITAO, Daniela Souza; PASQUALUCCI, Carlos Augusto; ANDRADE, Renato Araujo de; SILVA, Luiz Fernando Ferraz da; YAHAGI-ESTEVAM, Maristella; LAGE, Silvia Helena Gelas; LEITE, Renata Elaine Paraizo; CAMPO, Alexandre Brincalepe; SUEMOTO, Claudia KimieBackground Inflammation of the perivascular adipose tissue (PvAT) may be related to atherosclerosis; however, the association of polarized macrophages in the pericoronary PvAT with measurements of atherosclerosis components in humans has not been fully investigated. Methods and Results Coronary arteries were dissected with surrounding PvAT. We evaluated the percentage of arterial obstruction, intima-media thickness, fibrous cap thickness, plaque components, and the number of vasa vasorum. The number of proinflammatory (M1) and anti-inflammatory (M2) macrophages in the periplaque and control PvAT were evaluated using immunohistochemistry. Regression models adjusted for sociodemographic and clinical variables were used. In 319 segments from 82 individuals, we found a correlation of the M1/M2 macrophage density ratio with an increase in arterial obstruction (P=0.02) and lipid content (P=0.01), and a decrease in smooth muscle cells (P=0.02). M1 and the ratio of M1/M2 macrophages were associated with an increased risk of thrombosis (P=0.03). In plaques with thrombosis, M1 macrophages were correlated with a decrease in fibrous cap thickness (P=0.006), an increase in lipid content (P=0.008), and the number of vasa vasorum in the adventitia layer (P=0.001). M2 macrophages were correlated with increased arterial obstruction (P=0.01), calcification (P=0.02), necrosis (P=0.03) only in plaques without thrombosis, and decrease of the number of vasa vasorum in plaques with thrombosis (P=0.003). Conclusions M1 macrophages in the periplaque PvAT were associated with a higher risk of coronary thrombosis and were correlated with histological components of plaque progression and destabilization. M2 macrophages were correlated with plaque size, calcification, necrotic content, and a decrease in the number of vasa vasorum in the adventitia layer.
- Risk and protective factors for dementia: epidemiological evidence and windows of opportunity(2022) SUEMOTO, C. K.; NITRINI, R.; GRINBERG, L. T.; LEITE, R. E. P.; PASQUALLUCCI, C. A.; BERTOLA, L.; VIDAL-FERREIRA, N.; SZLEFJ, C.; CARAMELLI, P.; BENSENOR, I. M.; LOTUFO, P. A.; ALIBERTI, M. J. R.; FERRI, C. P.; JACOB-FILHO, W.Background: Most people with dementia already live in low- to middle-income countries (LMIC). However, most evidence regarding dementia prevention comes from high-income countries that have different socioeconomic status (SES) and risk factors prevalence than LMIC. In this session, we will present results on risk and protective factors for dementia from the Longitudinal Study of Adult Health (ELSA-Brasil), the Brazilian Longitudinal Study of Aging (ELSI-Brazil), and the Brazilian Biobank for Aging Studies (BAS). Method: The ELSA-Brasil follows 15,105 public servants since 2008-10. The ELSI-Brazil is a nationally representative study with 9,412 adults aged 50 years and older, who were enrolled in 2015-16. The BAS is a neuropathology study that started in 2004 and is the largest brain bank in Latin America with a collection of 1,441 brains. The focus of this presentation will be on the associations of education, SES, and cardiovascular factors with dementia using data from these three studies. Result: In the BAS, 77% of the sample has less than 5 years of education and 56% unskilled occupations. Compared to the group without education, those with formal education had better cognitive performance (1-4 years: β = -0.99, 95%CI = –1.85; –0.14, p = 0.02; ≥5 years: = –1.42, 95% CI = –2.47; –0.38, p = 0.008). On the other hand, occupation complexity and demands were unrelated to cognition. Similarly, we showed that education and early-life SES were the main contributors to cognitive performance in the ELSA-Brasil, while later SES had a lower influence on cognitive scores. Cardiovascular factors are also important contributors to brain health. Ideal vascular health was related to better cognitive function in the ELSA-Brasil. Participants with intermediate (β = 0.064, 95%CI = 0.033; 0.096) and optimal health (β = 0.108, 95%CI = 0.052; 0.164) had better cognitive z-scores. Moreover, carotid artery atherosclerosis evaluated by morphometric measurements was related to cognitive impairment in BAS and with cognitive decline in the ELSA-Brasil after 8 years of follow-up (β = -0.028, 95%CI = -0.036; -0.020, p<0.001). Finally, hypertension was related to worse cognition (β = -0.09; 95%CI = -0.15, -0.04; p = 0.001) in ELSI-Brazil, mainly in non-frail participants. Conclusion: Studies from LMIC regarding dementia risk factors are essential to implement tailored public policies for dementia primary prevention. © 2022 the Alzheimer's Association.
article 0 Citação(ões) na Scopus Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil(2022) NEVES, Beatriz Astolfi; NUNES, Paula Villela; RODRIGUEZ, Roberta Diehl; HAIDAR, Atmis Medeiros; LEITE, Renata Elaine Paraizo; NASCIMENTO, Camila; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; JACOB-FILHO, Wilson; LAFER, Beny; GRINBERG, Lea TenenholzObjective: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. Methods: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. Results: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P= 0.023), AD+VaD (P= 0.046), and DLB (P= 0.043) groups. In addition, VaD (P= 0.041) and AD+VaD (P= 0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. Conclusion: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.- Global and local ancestry modulate APOE association with Alzheimer's neuropathology and cognitive outcomes in an admixed sample(2022) NASLAVSKY, Michel Satya; SUEMOTO, Claudia K.; BRITO, Luciano Abreu; SCLIAR, Marilia Oliveira; FERRETTI-REBUSTINI, Renata Eloah; RODRIGUEZ, Roberta Diehl; LEITE, Renata E. P.; ARAUJO, Nathalia Matta; BORDA, Victor; TARAZONA-SANTOS, Eduardo; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos; NITRINI, Ricardo; YAFFE, Kristine; ZATZ, Mayana; GRINBERG, Lea T.Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE epsilon 4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE epsilon 4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE epsilon 4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE epsilon 4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE epsilon 4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE epsilon 4 risk compared to European ancestry.
- Microcephaly measurement in adults and its association with clinical variables(2022) COSTA, Nicole Rezende da; MANCINE, Livia; SALVINI, Rogerio; TEIXEIRA, Juliana de Melo; RODRIGUEZ, Roberta Diehl; LEITE, Renata Elaine Paraizo; NASCIMENTO, Camila; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; JACOB-FILHO, Wilson; LAFER, Beny; GRINBERG, Lea Tenenholz; SUEMOTO, Claudia Kimie; NUNES, Paula VillelaOBJECTIVE: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS: In our sample of 2,508 adults, the mean head circumference was 55.3 +/- 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) = 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION: Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.
- Identification of two patterns of mitochondrial DNA-copy number variation in postcentral gyrus during aging, influenced by body mass index and type 2 diabetes(2022) SEKIYA, Felipe Seiti; SILVA, Clarisse Pereira Nunes da; OBA-SHINJO, Sueli Mieko; SANTOS-BEZERRA, Daniele Pereira; RAVAGNANI, Felipe Gustavo; PASQUALUCCI, Carlos Augusto; GIL, Saulo; GUALANO, Bruno; BAPTISTA, Mauricio da Silva; CORREA-GIANNELLA, Maria Lucia; MARIE, Suely Kazue NagahashiAimsMitochondrial (mt) DNA replication is strongly associated with oxidative stress, a condition triggered by aging and hyperglycemia, both of which contribute to mitophagy disruption and inflammation. This observational exploratory study evaluated mtDNA-copy number (mtDNA-CN) and expression of genes involved in mitochondriogenesis (PPARGC1A, TFAM, TFB1M, TFB2M), mitophagy (PINK1, PRKN), and inflammatory pathways triggered by hyperglycemia (TXNIP, NLRP3, NFKB1), in the postcentral gyrus of adults and older individuals with and without type 2 diabetes mellitus (T2D).Main methodsQuantitative real-time PCR was employed to evaluate mtDNA-CN and gene expression; tissue autofluorescence, a marker of aging and of cells with damaged organelles, was also quantified.Key findingsNo correlation was found between age and mtDNA-CN, but a direct correlation was observed for cases with mtDNA-CN >1000 (r = 0.41). The mtDNA-CN >1000 group had greater tissue autofluorescence and higher body mass index compared to the mtDNA-CN <1000 group (BMI; 25.7 vs 22.0 kg/m(2), respectively). mtDNA-CN correlated with tissue autofluorescence in the overall sample (r = 0.55) and in the T2D group (r = 0.64). PINK and PRKN expressions were inversely correlated with age. Mitochondriogenesis genes and TXNIP expressions were higher in the T2D group, and correlations among the mitochondriogenesis genes were also stronger in this group, relative to the subgroup with mtDNA-CN >1000.
- Neuropathology of depression in non-demented older adults: A large postmortem study of 741 individuals(2022) NUNES, Paula Villela; SUEMOTO, Claudia Kimie; RODRIGUEZ, Roberta Diehl; LEITE, Renata Elaine Paraizo; NASCIMENTO, Camila; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; JACOB-FILHO, Wilson; GRINBERG, Lea T.; LAFER, BenyAssociations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. Seven hundred forty-one individuals (age at death = 72.2 +/- 11.7 years) from the Biobank for Aging Studies were analyzed. a-MDD was present in 54 (7.3%) participants, LLD in 80 (10.8%), and DS in 168 (22.7%). After adjustment for covariates and compared to controls, a-MDD, LDD and DS were associated with small vessel disease ( p = 0.039, p = 0.003, and p = 0.003 respectively); LLD, and DS were associated with brain infarcts ( p = 0.012, p = 0.018, respectively) and Lewy body disease ( p = 0.043, p = 0.002, respectively). DS was associated with betaamyloid plaque burden ( p = 0.027) and cerebral amyloid angiopathy ( p = 0.035) in cognitively normal individuals (Clinical Dementia Rating scale = 0). Vascular brain pathology was the strongest correlate of clinical depictions of depression in the absence of dementia, corroborating the vascular hypothesis of depression. Lewy body pathology underlay DS. An older adult with DS or LLD should be monitored for possible cognitive decline or neurodegenerative disorders.(c) 2022 Elsevier Inc. All rights reserved.