RICARDO NITRINI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
31 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 31
- The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex(2023) CASTRO-FONSECA, Emily; MORAIS, Viviane; SILVA, Camila G. da; WOLLNER, Juliana; FREITAS, Jaqueline; MELLO-NETO, Arthur F.; OLIVEIRA, Luiz E.; OLIVEIRA, Vilson C. de; LEITE, Renata E. P.; ALHO, Ana T.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; TOVAR-MOLL, Fernanda; LENT, RobertoThe human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has similar to 10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.
- Neuropathological correlates of neuropsychiatric symptoms in dementia(2023) GIBSON, Lucy L.; GRINBERG, Lea T.; FFYTCHE, Dominic; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; AARSLAND, Dag; SUEMOTO, Claudia K.Introduction Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. Methods In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). Results Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. Discussion LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.
- Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: a Neuropathological and Cognitive Study(2023) TOSCANO, Eliana C. B.; VIEIRA, Erica L. M.; GRINBERG, Lea T.; ROCHA, Natalia P.; BRANT, Joseane A. S.; PARADELA, Regina S.; GIANNETTI, Alexandre V.; SUEMOTO, Claudia K.; LEITE, Renata E. P.; NITRINI, Ricardo; RACHID, Milene A.; TEIXEIRA, Antonio L.Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age-and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid beta (A beta), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas A beta deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.
- Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome(2024) PARMERA, Jacy Bezerra; CARNEIRO, Camila de Godoi; ALMEIDA, Isabel Junqueira de; OLIVEIRA, Marcos Castello Barbosa de; BARBOSA, Pedro Melo; STUDART-NETO, Adalberto; ONO, Carla Rachel; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; BARBOSA, Egberto Reis; BRUCKI, Sonia Maria Dozzi; COUTINHO, Artur MartinsBackgroundCorticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category ""probable 4R-tauopathy"" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD).ObjectivesTo investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns.MethodsThirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18F]fluorodeoxyglucose and [11C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group.ResultsEleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata.ConclusionsThe 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.
- Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization(2023) CRIVELLI, Lucia; CALANDRI, Ismael Luis; SUEMOTO, Claudia Kimie; SALINAS, Rosa Maria; VELILLA, Lina Marcela; YASSUDA, Monica Sanches; CARAMELLI, Paulo; LOPERA, Francisco; NITRINI, Ricardo; SEVLEVER, Gustavo Emilio; SOSA, Ana Luisa; ACOSTA, Daisy; BAIETTI, Ana Maria Charamelo; CUSICANQUI, Maria Isabel; CUSTODIO, Nilton; SIMONE, Sergio Dansilio De; DERIO, Carolina Delgado; DUQUE-PENAILILLO, Lissette; DURAN, Juan Carlos; JIMENEZ-VELAZQUEZ, Ivonne Z.; LEON-SALAS, Jorge Mario; BERGAMO, Yanina; CLARENS, Maria Florencia; DAMIAN, Andres; DEMEY, Ignacio; HELOU, Maria Belen; MARQUEZ, Carlos; MARTIN, Maria Eugenia; MARTIN, Maria da Graca Morais; QUERZE, Diego; SURACE, Ezequiel Ignacio; ACOSTA-EGEA, Sabrina; AGUIRRE-SALVADOR, Esteban; SOUZA, Leonardo Cruz de; CANCADO, Gustavo Henrique da Cunha Peixoto; BRUCKI, Sonia Maria Dozzi; FRIEDLAENDER, Clarisse Vasconcelos; GOMES, Karina Braga; GUTIERREZ, Myriam; RIOS, Carlos Laforcada; GALINDO, Joyce Graciela Martinez; MONTESINOS, Rosa; NUNEZ-HERRERA, Alberto; OSPINA-HENAO, Sebastian; RODRIGUEZ, Guillermina; MASSON, Victoria Ruiz; SANCHEZ, Monica; SCHENK, Christian E.; SOTO, Ligia; BARBOSA, Maira Tonidandel; TOSATTI, Jessica Abdo Goncalves; VICUNA, Yosselin; ESPELAND, Mark; HAKANSSON, Krister; KIVIPELTO, Miia; BAKER, Laura; SNYDER, Heather; CARRILLO, Maria; ALLEGRI, Ricardo FranciscoINTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.
- Modified Brief Cognitive Screening Battery - Indonesian Version: cross-cultural adaptation and normative data based on demographic factors in North Sumatra, Indonesia(2024) FITRI, Fasihah Irfani; NACI, Lorina; TURANA, Yuda; RAMBE, Aldy Safruddin; NAZRIANI, Dina; NITRINI, Ricardo; CARAMELLI, PauloIntroductionKey component of early detection of dementia is a brief and culturally appropriate cognitive screening tool. This study aimed to perform a cultural adaptation of the Brief Cognitive Screening Battery (BCSB) and to obtain normative data from the older adult population.MethodsCross-cultural adaptation process to develop BCSB-INA was performed. This was followed by a feasibility study from community dwelling older adults from several urban and rural areas in North Sumatra, Indonesia.ResultsThe BCSB-INA was generally well understood and showed not much discrepancy in translation from the original version. There were differences in semantic and phonemic fluency and CDT based on years of education, but no difference was found on other domain, including the delayed recall of the FMT. The battery was more influenced by age than education.DiscussionThe BCSB-INA is culturally appropriate and feasible to be used in population with heterogenous educational background in Indonesia.
- Apolipoprotein E 62 allele is associated with lower risk of carotid artery obstruction in a population-based autopsy study(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 KimieIntroduction: Apolipoprotein E (APOE) 64 allele has been associated with higher carotid atherosclerosis risk, while the APOE-62 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric measurements of carotid atherosclerosis in an autopsy study with an admixed sample.Methods: We measured the intima-media thickness (IMT) and stenosis of the common (CCA) and internal carotid (ICA) arteries. The APOE polymorphisms were determined by real-time polymerase chain reaction. Participants were classified into three groups according to the APOE alleles (62, 63, and 64). We evaluated the association between APOE groups and carotid atherosclerosis using adjusted regression models and included interaction terms of APOE alleles with age, sex, and race. Results: We evaluated 1,850 carotid artery samples from 185 participants (mean age=75 & PLUSMN;12 years old, 55% female, and 71% White). The APOE-62 group (n=17) had a lower carotid obstruction and a lower number of severe stenoses (& GE; 70%). Having at least one 64 allele (n=51) was not associated with carotid atherosclerosis. APOE alleles were also not associated with carotid IMT. Age, sex, and race did not modify these relationships.Conclusion: APOE-62 carriers had a lower percentage of carotid obstruction and less severe stenosis. APOE-64 was not related to a higher risk of carotid atherosclerosis in this cross-sectional population-based autopsy study.
- Current clinical and research practices on frontotemporal dementia in Brazil: a national survey(2023) SOUZA, Leonardo Cruz de; BRUCKI, Sonia Maria Dozzi; SCHILLING, Lucas Porcello; SILVA, Leticia Costa da; TAKADA, Leonel Tadao; BAHIA, Valeria Santoro; BARBOSA, Breno Jose Alencar Pires; BALTHAZAR, Marcio Luiz Figueredo; FROTA, Norberto Anizio Ferreira; NITRINI, Ricardo; CARAMELLI, Paulo; SMID, JerusaBackground Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care.Objective The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil.Methods We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology ( n = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 ( n = 187). The invitation was also diffused through social media.Results 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) ( n = 211), bipolar disorder ( n = 117) and dementia with Lewy bodies ( n = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively.Conclusions The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil.
- Risk factors for dementia in Brazil: Differences by region and race(2023) SUEMOTO, Claudia K.; MUKADAM, Naaheed; BRUCKI, Sonia M. D.; CARAMELLI, Paulo; NITRINI, Ricardo; LAKS, Jerson; LIVINGSTON, Gill; FERRI, Cleusa P.Introduction Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. Methods We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. Results The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. Discussion Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.
- Predicting Dementia Due to Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia Using Algorithms with the Addenbrooke's Cognitive Examination-Revised Subscores Combined with Sociodemographic Factors(2023) AMARAL-CARVALHO, Viviane; LIMA-SILVA, Thais Bento; MARIANO, Luciano Inacio; SOUZA, Leonardo Cruz de; GUIMARAES, Henrique Cerqueira; BAHIA, Valeria Santoro; NITRINI, Ricardo; BARBOSA, Maira Tonidandel; YASSUDA, Monica Sanches; CARAMELLI, PauloBackground: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders.Objective: The objectibe of this study is to investigate the value of the ACE-R combined with sociodemographic factors in the differential diagnosis between AD and bvFTD.Methods The ACE-R was administered to 102 patients with mild dementia due to probable AD, 37 with mild bvFTD, and 135 controls. Performances of patients and controls were analyzed by logistic regression and by ROC curves to refine the diagnostic accuracy of the ACE-R in AD and bvFTD.Results: The ACE-R subscores Attention and Orientation, Fluency, and Memory, in combination with schooling differentiated AD from controls with an area under the ROC curve (AUC) of 0.936 (86% sensitivity and 87% specificity). The ACE-R subscores Attention and Orientation, Fluency, and Language, in combination with sex (male), age, and schooling, discriminated bvFTD from controls with an AUC of 0.908 (81% sensitivity and 95% specificity). In the differentiation between AD and bvFTD, the ACE-R subscores Attention and Orientation, Fluency, and Language, together with age, displayed an AUC of 0.865 (78% sensitivity and 85% specificity).Conclusion: The combination of ACE-R scores with sociodemographic data allowed good differentiation between AD and bvFTD in the study sample.