Artigos e Materiais de Revistas Científicas - LIM/22
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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.
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- Advances in diffuse glial tumors diagnosis(2023) GODOY, Luis Filipe de Souza; PAES, Vitor Ribeiro; AYRES, Aline Sgnolf; BANDEIRA, Gabriela Alencar; MORENO, Raquel Andrade; HIRATA, Fabiana de Campos Cordeiro; SILVA, Frederico Adolfo Benevides; NASCIMENTO, Felipe; CAMPOS NETO, Guilherme de Carvalho; GENTIL, Andre Felix; LUCATO, Leandro Tavares; AMARO JUNIOR, Edson; YOUNG, Robert J.; MALHEIROS, Suzana Maria FleuryIn recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.
- Malignant neoplasm of breast in Brazilian women: A cross-sectional study from 2008 to 2019(2023) JUSTO, Alberto Fernando O.; COLLACO, Rita de Cassia; LESCANO, Caroline Honaiser; OLIVEIRA, Ivan Pires deObjective: Breast cancer is the most lethal malignancy for women worldwide. Developed countries, such as Portugal, Spain, and the United States, have declining mortality rates due to breast cancer; however, in developing countries, the epidemiological reports are scarce. In this context, the aims of this study are to describe and discuss the female breast cancer profile of hospitalization and mortality according to age and geographic region in Brazil from 2008 to 2019.Methods: Data were obtained from the National Health System Department of Informatics (DATASUS), maintained by the Brazilian Ministry of Health, which includes the registers of hospitalization and mortality by malignant neoplasm of breast (code C50, ICD-10). Proportional rates of hospitalization and deaths were estimated per 100,000 inhabitants according to respective subjects' age, region, and year of the occurrence.Results: From 2008 to 2019, 643,822 hospital admissions due to malignant neoplasm of breast were reported in Brazil, of which the South and Southeast regions were the most prevalent. Higher hospitalization rates were seen in subjects aged 50-79-years-old. Regarding mortality, 53,480 deaths by breast cancer were reported; similarly to hospitalization, the Southeast and South were the most affected regions. Mortality rates have increased over time in different magnitudes depending on subjects' age.Conclusion: We have shown an increase in morbidity and mortality over time, which is dependent on patients' age and region. The results presented here may contribute to the ongoing discussion about the role and future perspectives of the Brazilian health care system, especially regarding to the strategies for the prevention, control, and treatment of breast cancer.
- Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART(2023) EHRENBERG, Alexander J.; KELBERMAN, Michael A.; LIU, Kathy Y.; DAHL, Martin J.; WEINSHENKER, David; FALGAS, Neus; DUTT, Shubir; MATHER, Mara; LUDWIG, Mareike; BETTS, Matthew J.; WINER, Joseph R.; TEIPEL, Stefan; WEIGAND, Alexandra J.; ESCHENKO, Oxana; HAEMMERER, Dorothea; LEIMAN, Marina; COUNTS, Scott E.; SHINE, James M.; ROBERTSON, Ian H.; LEVEY, Allan I.; LANCINI, Elisa; SON, Gowoon; SCHNEIDER, Chrisoph; EGROO, Maxime Van; LIGUORI, Claudio; WANG, Qin; VAZEY, Elena M.; RODRIGUEZ-PORCEL, Federico; HAAG, Lena; BONDI, Mark W.; VANNESTE, Sven; FREEZE, Whitney M.; YI, Yeo-Jin; MALDINOV, Mihovil; GATCHEL, Jennifer; SATPATI, Abhijit; BABILONI, Claudio; KREMEN, William S.; HOWARD, Robert; JACOBS, Heidi I. L.; GRINBERG, Lea T.The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HighlightsNeuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages.Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration.Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia.Biomarkers of neuromodulatory integrity would be value-creating for dementia care.Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.
- Neuronal and glial vulnerability of the suprachiasmatic nucleus in tauopathies: evidence from human studies and animal models(2024) SON, Gowoon; NEYLAN, Thomas C.; GRINBERG, Lea T.Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.
- Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample(2023) PARADELA, Regina Silva; JUSTO, Alberto Fernando Oliveira; PAES, Vitor Ribeiro; 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 epsilon 4 allele (APOE-epsilon 4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-epsilon 4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.Methods: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-epsilon 4 carriers (at least one epsilon 4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-epsilon 4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).Results: We included 648 participants (mean age 75 +/- 12 years old, mean education 4.4 +/- 3.7 years, 52% women, 69% White, and 28% APOE-epsilon 4 carriers). The association between APOE-epsilon 4 and cognitive abilities was mediated by neurofibrillary tangles (beta = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (beta = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-epsilon 4 to cognition.Conclusion: The association between APOE-epsilon 4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-epsilon 4 and cognition.
- Aren't you forgetting something? Cognitive screening beyond delirium in the emergency department(2023) MORAES, Gabriel Stanziola de; CURIATI, Pedro K.; AVELINO-SILVA, Thiago Junqueira; MORINAGA, Christian V.; APOLINARIO, Daniel; SUEMOTO, Claudia Kimie; ALIBERTI, Marlon Juliano Romero
- Untangle the relationship of muscle mass and bone mineral content on handgrip strength: Results of ELSA-Brasil(2023) TAVARES, Nayranne Hivina Carvalho; RODRIGUES, Brena Custodio; ARRUDA, Soraia P. M.; SZLEJF, Claudia; SUEMOTO, Claudia Kimie; GRIEP, Rosane Harter; DINIZ, Maria de F. H. S.; GIATTI, Luana; BARRETO, Sandhi M.; FORTUNATO, LarissaThe study aims to investigate the independent association of muscle mass (MM) and bone mineral content (BMC) in the performance of the handgrip strength (HGS) test and whether there is effect modification by sex and age. In 12,491 participants from the ELSA-Brasil we estimated the associations between MM, BMC and HGS using linear regression models. All the analyses were performed for total population, also stratified for sex and age. For total population an interaction term was included between each explanatory variable of interest with sex and age to verify the presence of effect modification. We observed that the higher quintiles of MM and BMC were associated to an increasing in the mean of HGS compared to the first quintile, with greater magnitudes in men compared to women, also adults compared to elderly. When we estimated the independent effect of each exposure of interest, MM showed stronger effect in HGS in women, men and adults then BMC. In conclusion, we observed that higher amounts of MM and BMC are associated with higher HGS, regardless of sociodemographic characteristics, health conditions and lifestyle, with this effect being greater in men and adults.
- 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.
- Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study(2024) BICALHO, Maria Aparecida Camargos; ALIBERTI, Marlon Juliano Romero; DELFINO-PEREIRA, Polianna; CHAGAS, Victor Schulthais; ROSA, Patryk Marques da Silva; PIRES, Magda Carvalho; RAMOS, Lucas Emanuel Ferreira; BEZERRA, Adriana Falangola Benjamin; FERES, Ana Beatriz de Castro; GOMES, Angelica Gomides dos Reis; BHERING, Angelinda Rezende; PESSOA, Bruno Porto; SILVA, Carla Thais Candida Alves da; CIMINI, Christiane Correa Rodrigues; SUEMOTO, Claudia Kimie; DIAS, Cristiana Andrade Coelho; CARAZAI, Daniela dos Reis; PONCE, Daniela; RIOS, Danyelle Romana Alves; MANENTI, Euler; ANSCHAU, Fernando; BATISTA, Joanna d'Arc Lyra; ALVARENGA, Joice Coutinho de; VIGUINI, Julia Avancini; ZANELLATO, Julia Mariot; RUGOLO, Juliana Machado; RUSCHEL, Karen Brasil; NASCIMENTO, Leticia do; MENEZES, Luanna Silva Monteiro; OLIVEIRA, Lucas Moyses Carvalho de; CASTRO, Luis Cesar de; NASI, Luiz Antonio; CARNEIRO, Marcelo; FERREIRA, Maria Angelica Pires; GODOY, Mariana Frizzo de; GUIMARAES-JUNIOR, Milton Henriques; OLIVEIRA, Neimy Ramos de; ZIEGELMANN, Patricia Klarmann; PORTO, Paula Fonseca; MENDES, Paulo Mascarenhas; PARAISO, Pedro Gibson; REIS, Priscilla Pereira dos; FRANCISCO, Saionara Cristina; ARAUJO, Silvia Ferreira; AVELINO-SILVA, Thiago Junqueira; MARCOLINO, Milena SorianoBackground Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia.Methods This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged >= 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events.Results Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups.Conclusion Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.
- Advancing cognitive assessment in telemedicine: Validity and reliability of the telephone 10-point cognitive screener(2023) RICO, Bruno Marcondes Hottum; ALIBERTI, Marlon Juliano Romero; SILVA, Natalia Oliveira Trajano da; BUSSE, Alexandre Leopold; SUEMOTO, Claudia Kimie; AVELINO-SILVA, Thiago Junqueira; MAGALDI, Regina Miksian; APOLINARIO, Daniel
- Content validity evidence of the Brazilian version of the Cognitive Symptom Checklist-Work-21(2023) ROCHA, Elaine Cristina Lopes da; SOUSA, Kayo Henrique Jardel Feitosa; LUCCHESI, Paola Alves de Oliveira; FARIA, Magda Guimaraes de Araujo; BALBINOTTI, Marcos Alencar Abaide; REBUSTINI, Flavio; FERRETTI-REBUSTINI, Renata Eloah de Lucena; GALLASCH, Cristiane HelenaObjective: to cross-culturally adapt and assess the content validity evidence of the Cognitive Symptom Checklist-Work-21 for the Brazilian context. Method: a psychometric study of cross-cultural adaptation, covering the stages of translation, reconciliation, back-translation, intercultural equivalence assessment and content validity evidence analysis, considering Content Validity Ratio parameters in breast cancer survivors. Results: the translations were equivalent to the original version. Colloquial expressions were modified, tense, verbal adjusted, and two items containing multiple commands were separated. The final version now contains 22 items, presenting semantic, conceptual, idiomatic and experimental equivalences. The pre-test indicated good understanding and ease in the response process. Conclusion: the final version was defined as ""Lista de verificacao de sintomas cognitivos relacionados ao trabalho -22 itens"", showing good linguistic equivalence and strong evidence of content validity in the Brazilian context.
- The applicability of the ""surprise question"" as a prognostic tool in patients with severe chronic comorbidities in a university teaching outpatient setting(2023) LIN, C. A.; PIRES, P. P.; FREITAS, L. V.; REIS, P. V. S.; SILVA, F. D.; HERBST, L. G.; NUNES, R.; LIN, C. J.; NUNES, M. P. T.Background Life expectancy in recent decades has increased the prevalence of chronic diseases in the population, requiring an approach to new health topics, such as discussions on quality of life and expectations about death and dying. The concept of advance directives (ADs) gives individuals the opportunity to make known their decisions about the treatments they would like to receive at the end of life. Despite the recognition of relevance in clinical practice, the applicability of the concept presents challenges, including establishing the appropriate prognosis for each patient and the ideal time to approach the patient. Some prognostic tools were developed, such as the surprise question (SQ): ""Would you be surprised if your patient died in 12 months?"", which is used in some clinical settings to predict patient deaths and to make decisions regarding ADs. The main objective of the present study was to evaluate the behavior of second-year resident physicians (PGY-2) when the SQ was applied. Method In our observational study, from July 1, 2016, to February 28, 2017, (PGY-2) in the Internal Medicine Residency Program (IMRP) applied SQ to all patients with multiple and varied chronic no communicable comorbidities, who were followed up at the general medicine outpatient clinic (GMOC) of a tertiary university hospital in Sao Paulo- Brazil. The frequency of the outcome (death or non-death within 12 months) was analyzed by correlating it with the clinical data (impact of the studied variables). Results Eight hundred forty patients entered the study. Fitfty-two of them (6.2%) died within one year. PGY-2 predicted that two hundred and fourteen patients (25.5% of total) would die within a year (answer No to SQ), of which, 32 (14.9%) did so. The correct residents' prognosis for the subgroup of 626 patients (answer ""Yes"" to SQ) was NPV = 96.8% (CI = 95.4%-98.2%) and PPV = 14.9% (CI 10.1%-19, 6%). Answering ""Yes"" to SQ correlated negatively to addressing AD while the outcomes death and the answer No to SQ were positively correlated, according to the number of comorbidities. Conclusion The SQ, in addition to care, contributed to health education, communication and care planning shared by the doctor and patient.
- Alzheimer's disease phenotypes show different sleep architecture(2023) FALGAS, Neus; WALSH, Christine M.; YACK, Leslie; SIMON, Alexander J.; ALLEN, Isabel E.; KRAMER, Joel H.; ROSEN, Howard J.; JOIE, Renaud La; RABINOVICI, Gil; MILLER, Bruce; SPINA, Salvatore; SEELEY, William W.; RANASINGHE, Kamalini; VOSSEL, Keith; NEYLAN, Thomas C.; GRINBERG, Lea T.IntroductionSleep-wake disturbances are a prominent feature of Alzheimer's disease (AD). Atypical (non-amnestic) AD syndromes have different patterns of cortical vulnerability to AD. We hypothesized that atypical AD also shows differential vulnerability in subcortical nuclei that will manifest as different patterns of sleep dysfunction. MethodsOvernight electroencephalography monitoring was performed on 48 subjects, including 15 amnestic, 19 atypical AD, and 14 controls. AD was defined based on neuropathological or biomarker confirmation. We compared sleep architecture by visual scoring and spectral power analysis in each group. ResultsOverall, AD cases showed increased sleep fragmentation and N1 sleep compared to controls. Compared to atypical AD groups, typical AD showed worse N3 sleep dysfunction and relatively preserved rapid eye movement (REM) sleep. DiscussionResults suggest differing effects of amnestic and atypical AD variants on slow wave versus REM sleep, respectively, corroborating the hypothesis of differential selective vulnerability patterns of the subcortical nuclei within variants. Optimal symptomatic treatment for sleep dysfunction in clinical phenotypes may differ. HighlightsAlzheimer's disease (AD) variants show distinct patterns of sleep impairment.Amnestic/typical AD has worse N3 slow wave sleep (SWS) impairment compared to atypical AD.Atypical AD shows more rapid eye movement deficits than typical AD.Selective vulnerability patterns in subcortical areas may underlie sleep differences.Relatively preserved SWS may explain better memory scores in atypical versus typical AD.
- The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States(2023) SIMON, Sharon Sanz; BRUCKI, Sonia Maria Dozzi; FONSECA, Luciana Mascarenhas; BECKER, Jacqueline; CAPPI, Carolina; MARQUES, Andrea Horvath; HEYN, Patricia C.; GONCALVES, Priscila Dib; MARTINS, Silvia S.; BUSATTO, Geraldo; SUEMOTO, Claudia Kimie; NITRINI, Ricardo; CARAMELLI, Paulo; YASSUDA, Monica Sanches; MIOTTO, Eliane Correa; GRINBERG, Lea Tenenholz; RENTERIA, Miguel Arce; ALEGRIA, Margarita; STERN, Yaakov; RIVERA-MINDT, Monica; BERTOLA, LaissIntroduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities. It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population.Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles.Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials.Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities.
- The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States ( vol 9, e12425, 2023)(2023) SIMON, Sharon Sanz; BRUCKI, Sonia Maria Dozzi; FONSECA, Luciana Mascarenhas; BECKER, Jacqueline; CAPPI, Carolina; MARQUES, Andrea Horvath; HEYN, Patricia C.; GONCALVES, Priscila Dib; MARTINS, Silvia S.; BUSATTO, Geraldo; BERTOLA, Laiss; SUEMOTO, Claudia Kimie; NITRINI, Ricardo; CARAMELLI, Paulo; YASSUDA, Monica Sanches; MIOTTO, Eliane Correa; GRINBERG, Lea Tenenholz; RENTERIA, Miguel Arce; ALEGRIA, Margarita; STERN, Yaakov; RIVERA-MINDT, Monica
- Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice(2023) RIBEIRO, Felipe C.; COZACHENCO, Danielle; HEIMFARTH, Luana; FORTUNA, Juliana T. S.; FREITAS, Guilherme B. de; SOUSA, Jorge M. de; ALVES-LEON, Soniza V.; LEITE, Renata E. P.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; FELICE, Fernanda G. De; LOURENCO, Mychael V.; FERREIRA, Sergio T.The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in post-mortem AD hippocampi compared to controls. Using several experimental models, we show that amyloid-beta oligomers (A beta Os) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1 Delta E9 mice. Reduced synaptic proteasome activity instigated by A beta Os is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks A beta O-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in AD. A study involving several research models suggests that the function and synaptic localization of proteasomes, intracellular machineries involved in protein degradation, are impaired in the brains affected by Alzheimer's disease.
- Association between carotid intima-media thickness and cognitive decline differs by race(2023) FERREIRA, Naomi Vidal; BERTOLA, Laiss; SANTOS, Itamar S.; GOULART, Alessandra C.; BITTENCOURT, Marcio S.; BARRETO, Sandhi Maria; GIATTI, Luana; CARAMELLI, Paulo; PEREIRA, Alexandre; LOTUFO, Paulo Andrade; BENSENOR, Isabela M.; SUEMOTO, Claudia KimieIntroductionCommon carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis and is associated with cognitive decline. Although carotid atherosclerosis is more frequent in White than in Black participants, little is known whether race modifies the association between cIMT and cognitive decline. MethodsIn this longitudinal analysis of the ELSA-Brasil, we assessed cIMT using ultrasound and cognitive performance using different domain tests. We used linear mixed models, interaction analysis, and race stratified analyses. ResultsBaseline high IMT values were associated with memory (p < 0.001), verbal fluency (p < 0.001), TMT-B (p < 0.001)), and global cognitive decline (p < 0.001). Race was an effect modifier in the association between IMT and global cognitive decline (0.043), with stronger association in White (p < 0.001) than in Black (p = 0.009) participants. DiscussionBaseline IMT was associated with global and domain-specific cognitive decline and race modified this relationship, with stronger associations in White participants. HighlightsCarotid intima-media thickness (cIMT) was associated with cognitive decline.cIMT and cognitive decline association was stronger in White than in Black participants.We used inverse probability weighting to address attrition bias.
- The action of phosphodiesterase-5 inhibitors on β-amyloid pathology and cognition in experimental Alzheimer's disease: A systematic review (vol 320, 121570, 2023)(2023) JUSTO, Alberto Fernando Oliveira; TOSCANO, Eliana Cristina de Brito; FARIAS-ITAO, Daniela Souza; SUEMOTO, Claudia Kimie
- 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.
- Education and cognitive function among older adults in Brazil and Mexico(2023) GONCALVES, Natalia Gomes; AVILA, Jaqueline Contrera; BERTOLA, Laiss; OBREGON, Alejandra Michaels; FERRI, Cleusa Pinheiro; WONG, Rebeca; SUEMOTO, Claudia KimieEducation is protective against cognitive impairment. We used nationally representative data from Mexico and Brazil to assess the association between education and cognitive function. The sample included adults & GE; 50 years from the Brazilian Longitudinal Study of Aging (ELSI) and the Mexican Health and Aging Study (MHAS). Participants were classified as cognitively impaired or not impaired. We used logistic regression models to estimate the association between education and cognitive function. Education level was higher in MHAS than in ELSI. Participants with at least 1 year of education were less likely to have cognitive impairment than those with no formal education in both cohorts. Men in ELSI had higher odds for cognitive impairment compared to men in MHAS. In both cohorts, higher educational level was associated with lower odds of cognitive impairment compared to no formal education. Sex was an effect modifier in MHAS but not in ELSI.HIGHLIGHTSCognitive test batteries were harmonized using a regression-based approach.Even very low levels of education were associated with reduced odds of cognitive impairment compared to no formal education.Brazilians were more likely to have cognitive impairment than Mexicans given the same education level.The differences in the association of education with cognition between Brazil and Mexico were only observed among men.