WILSON JACOB FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
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- Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis(2018) NASCIMENTO, C.; ALHO, A. T. Di Lorenzo; AMARAL, C. Bazan Conceicao; LEITE, R. E. P.; NITRINI, R.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; HOKKANEN, S. R. K.; HUNTER, S.; KEAGE, H.; KOVACS, G. G.; GRINBERG, L. T.; SUEMOTO, C. K.ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
- Persistent pain and cognitive decline in older adults: a systematic review and meta-analysis from longitudinal studies(2020) AGUIAR, Gabriella Pequeno Costa Gomes de; SARAIVA, Marcos Daniel; KHAZAAL, Eugenia Jatene Bou; ANDRADE, Daniel Ciampi de; JACOB-FILHO, Wilson; SUEMOTO, Claudia KimieBoth persistent pain and cognitive decline prevalence increase with advancing age and are associated with functional decline. However, the association of pain and cognitive decline has not been evaluated yet by a systematic assessment of longitudinal studies. We aimed to assess the association of persistent pain as a risk factor for cognitive decline in community older adults, using data from longitudinal studies in a systematic review and meta-analysis. Publications were identified using a systematic search on PubMed, EMBASE, and Cochrane Library databases from inception to June 2019. Because heterogeneity across studies was high, we used random-effects meta-analysis to calculate the pooled relative risk (RR) for the association between persistent pain and cognitive decline incidence. We investigated sources of heterogeneity among studies using meta-regression and stratified analyses. We included 10 prospective longitudinal studies with 57,495 participants with a mean age at the baseline ranging from 61.8 to 88.4 years and mean follow-up times ranging from 2.75 to 11.8 years. Persistent pain at baseline was not associated with the development of cognitive decline during the follow-up (pooled RR = 1.05, 95% confidence interval = 0.92-1.21). In sensitivity analyses, only length of follow-up time <= 4.5 years was associated with a higher risk of cognitive impairment (pooled RR = 1.19, 95% confidence interval = 1.10-1.28). Persistent pain was not associated with the incidence of cognitive decline.
- Review of Decision-Making in Game Tasks in Elderly Participants with Alzheimer Disease and Mild Cognitive Impairment(2017) SIQUEIRA, Alaise Silva Santos de; YOKOMIZO, Juliana Emy; JACOB-FILHO, Wilson; YASSUDA, Monica Sanches; APRAHAMIAN, IvanBackground: Changes in decision-making (DM) have recently been investigated in patients with Alzheimer disease (AD) or mild cognitive impairment (MCI). DM is highly relevant to everyday functioning and autonomy. It relies on several cognitive abilities, such as semantic and episodic memory, as well as aspects of executive functioning. We conducted a systematic review of DM in older adults with MCI and AD. Summary: Only 5 studies whose main objective was to evaluate the DM performance were selected. The results extracted indicated that DM in ambiguity and in at-risk situations are both impaired in probable AD patients. MCI patients have difficulty making advantageous decisions under ambiguity and at risk, similar to patients with probable AD but they are less impaired. Key Messages: DM deficits may be a predictor of cognitive impairment and conversion to dementia and its potential clinical value should be further explored in longitudinal studies involving direct comparison between MCI and AD patients. (C) 2017 S. Karger AG, Basel.
- 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.