LEA TENENHOLZ GRINBERG
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, 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
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Chronic Traumatic Encephalopathy Presenting as Alzheimer's Disease in a Retired Soccer Player(2016) GRINBERG, Lea T.; ANGHINAH, Renato; NASCIMENTO, Camila Fernandes; AMARO JR., Edson; LEITE, Renata P.; MARTIN, Maria da Graca M.; NASLAVSKY, Michel S.; TAKADA, Leonel T.; JACOB FILHO, Wilson; PASQUALUCCI, Carlos A.; NITRINI, RicardoThe relationship between soccer and chronic traumatic encephalopathy (CTE) is not well established. We report clinicopathological correlations in an 83-year-old retired center-back soccer player, with no history of concussion, manifesting typical Alzheimer-type dementia. Examination revealed mixed pathology including widespread CTE, moderate Alzheimer's disease, hippocampal sclerosis, and TDP-43 proteinopathy. This case adds to a few CTE cases described in soccer players. Furthermore, it corroborates that CTE may present clinically as typical Alzheimer-type dementia. Further studies investigating the extent to which soccer is a risk for CTE are needed.
- Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease(2018) EHRENBERG, Alexander J.; SUEMOTO, Claudia K.; RESENDE, Elisa de Paula Franca; PETERSEN, Cathrine; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; FERRETTI-REBUSTINI, Renata Eloah de Lucena; YOU, Michelle; OH, Jun; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; KRAMER, Joel H.; GATCHEL, Jennifer R.; GRINBERG, Lea T.Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-beta pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of Sao Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-beta burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-beta pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.
- Subregional Basal Forebrain Atrophy in Alzheimer's Disease: A Multicenter Study(2014) KILIMANN, Ingo; GROTHE, Michel; HEINSEN, Helmut; ALHO, Eduardo Joaquim Lopez; GRINBERG, Lea; AMARO, Edson; SANTOS, Glaucia Aparecida Bento dos; SILVA, Rafael Emidio da; MITCHELL, Alex J.; FRISONI, Giovanni B.; BOKDE, Arun L. W.; FELLGIEBEL, Andreas; FILIPPI, Massimo; HAMPELL, Harald; KLOEPPEL, Stefan; TEIPEL, Stefan J.Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD.
- Neuropsychiatric Inventory in Community-Dwelling Older Adults with Mild Cognitive Impairment and Dementia(2019) NUNES, Paula Villela; SCHWARZER, Monise Caroline; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; RODRIGUEZ, Roberta Diehl; NASCIMENTO, Camila Fernandes; OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; LAFER, Beny; SUEMOTO, Claudia KimieBackground: Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. Objective: To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia. Methods: We included 1,565 participants (mean age = 72.7 +/- 12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia. Results: Participants were cognitively normal (CDR = 0; n = 1,062), MCI (CDR = 0.5; n = 145), or dementia (CDR >= 1.0, n = 358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUC = 0.755). Poor discrimination (AUC = 0.563) was found for the comparison of MCI and those cognitively normal. Conclusions: We found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores >= to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.
- Diabetes is Not Associated with Alzheimer's Disease Neuropathology(2017) MATIOLI, Maria Niures Pimentel dos Santos; SUEMOTO, Claudia Kimie; RODRIGUEZ, Roberta Diehl; FARIAS, Daniela Souza; SILVA, Magnolia Moreira da; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah Lucena; FARFEL, Jose Marcelo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; ARVANITAKIS, Zoe; NASLAYSKY, Michel Satya; ZATZ, Mayana; GRINBERG, Lea Tenenholz; NITRINI, RicardoBackground: Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low-and middle-income countries. Objective: To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. Methods: In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations. Results: Among 1,037 subjects (mean age = 74.4 +/- 11.5 y; mean education = 4.0 +/- 3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81-1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68-1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele epsilon 4 on the association between diabetes mellitus and BB scores. Conclusion: No evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele epsilon 4 carriers, had higher odds of accumulation of neurofibrillary tangles.
- Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer's Disease Pathogenesis(2015) THEOFILAS, Panos; DUNLOP, Sara; HEINSEN, Helmut; GRINBERG, Lea TenenholzPharmacological interventions in Alzheimer's disease (AD) are likely to be more efficacious if administered early in the course of the disease, foregoing the spread of irreversible changes in the brain. Research findings underline an early vulnerability of the isodendritic core (IC) network to AD neurofibrillary lesions. The IC constitutes a phylogenetically conserved subcortical system including the locus coeruleus in pons, dorsal raphe nucleus, and substantia nigra in the midbrain, and nucleus basalis of Meynert in basal forebrain. Through their ascending projections to the cortex, the IC neurons regulate homeostasis and behavior by synthesizing aminergic and cholinergic neurotransmitters. Here we reviewed the evidence demonstrating that neurons of the IC system show neurofibrillary tangles in the earliest stages of AD, prior to cortical pathology, and how this involvement may explain pre-amnestic symptoms, including depression, agitation, and sleep disturbances in AD patients. In fact, clinical and animal studies show a significant reduction of AD cognitive and behavioral symptoms following replenishment of neurotransmitters associated with the IC network. Therefore, the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in AD.