ABSTRACT
Abstract Introduction: Mild cognitive impairment (MCI) is a prevalent and underdiagnosed condition in chronic kidney disease (CKD), that shares common pathophysiological factors such as chronic inflammation. Objective: To evaluate the association of MCI in CKD stages 1-5 using inflammatory markers and changes by magnetic resonance imaging (MRI). Patients and Methods: Cross-sectional study in adult patients with pre-dialysis CKD. MCI was assessed by the Montreal Cognitive Assessment (MoCA) and the estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration equation. Sociodemographic and clinical data were collected from medical records. The cytokines IL-4, IL-6, IL-17, TNF-α and hs-CRP were determined. Brain MRI was performed in a 1.5 Tesla device, without paramagnetic contrast. A descriptive analysis followed by a comparison of abnormal versus normal MoCA scores among all studied variables. A linear regression analysis was performed using MoCA as a dependent variable, adjusted for confounding factors. Results: Of 111 invited patients, eighty completed the neuropsychological assessment and 56 underwent MRI, and were included in the study. Mean age was 56.3 ± 8.3 years and 51.8% (n = 29) had altered MoCA. When compared to the group with normal MoCA, the group with altered MoCA had higher levels of IL-6 and IL-17. There was no correlation between altered MoCA with eGFR or with MRI abnormalities. Conclusão: MCI assessed by MoCA was prevalent in patients with pre-dialysis CKD, it was associated with inflammation and showed no correlation with MRI changes.
Resumo Introdução: O comprometimento cognitivo leve (CCL) é prevalente e subdiagnosticado na doença renal crônica (DRC), condição com a qual compartilha fatores fisiopatológicos como a inflamação crônica. Objetivo: Avaliar a associação do CCL na DRC estágios 1 a 5, com marcadores inflamatórios e alterações de exames de imagem por ressonância magnética (RM). Pacientes e métodos: Estudo transversal em pacientes adultos, com DRC pré-dialítica. CCL foi avaliado pelo Montreal Cognitive Assessment (MoCA) e a taxa de filtração glomerular estimada (TFGe), pela equação do CKD-EPI. Dados sociodemográficos e clínicos foram coletados nos prontuários médicos. Dosadas citocinas IL-4, IL-6, IL-17, o TNF-α e PCR-us. A RM do encéfalo foi realizada em aparelho de 1,5 Tesla, sem contraste. Realizada análise descritiva seguida por comparação de pontuações do MoCA anormais versus normais entre todas as variáveis estudadas. A regressão linear foi realizada usando MoCA como uma variável dependente, ajustada para fatores de confusão. Resultados: De 111 pacientes convidados, oitenta completaram a avaliação neuropsicológica, 56 realizaram RM, tendo sido incluídos no estudo. A média de idade foi de 56,3 ± 8,3 anos e 51,8% (n = 29) apresentavam MoCA alterado. Quando comparado ao grupo MoCA normal, o grupo MoCA alterado apresentou níveis mais elevados de IL-6 e IL-17. Não houve correlação entre MoCA alterado com TFGe nem com anormalidades na RM. Nos modelos ajustados, a IL-6 foi preditor independente do MoCA alterado Conclusão: O CCL avaliado pelo MoCA foi prevalente em pacientes com DRC pré-dialítica, associou-se com inflamação e não apresentou correlação com alterações da RM.
ABSTRACT
INTRODUCTION: Mild cognitive impairment (MCI) is a prevalent and underdiagnosed condition in chronic kidney disease (CKD), that shares common pathophysiological factors such as chronic inflammation. OBJECTIVE: To evaluate the association of MCI in CKD stages 1-5 using inflammatory markers and changes by magnetic resonance imaging (MRI). PATIENTS AND METHODS: Cross-sectional study in adult patients with pre-dialysis CKD. MCI was assessed by the Montreal Cognitive Assessment (MoCA) and the estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration equation. Sociodemographic and clinical data were collected from medical records. The cytokines IL-4, IL-6, IL-17, TNF-α and hs-CRP were determined. Brain MRI was performed in a 1.5 Tesla device, without paramagnetic contrast. A descriptive analysis followed by a comparison of abnormal versus normal MoCA scores among all studied variables. A linear regression analysis was performed using MoCA as a dependent variable, adjusted for confounding factors. RESULTS: Of 111 invited patients, eighty completed the neuropsychological assessment and 56 underwent MRI, and were included in the study. Mean age was 56.3 ± 8.3 years and 51.8% (n = 29) had altered MoCA. When compared to the group with normal MoCA, the group with altered MoCA had higher levels of IL-6 and IL-17. There was no correlation between altered MoCA with eGFR or with MRI abnormalities. CONCLUSÃO: MCI assessed by MoCA was prevalent in patients with pre-dialysis CKD, it was associated with inflammation and showed no correlation with MRI changes.
Subject(s)
Cognitive Dysfunction , Renal Insufficiency, Chronic , Adult , C-Reactive Protein , Cognitive Dysfunction/epidemiology , Cross-Sectional Studies , Dialysis , Humans , Inflammation/complications , Interleukin-17 , Interleukin-4 , Interleukin-6 , Magnetic Resonance Imaging , Middle Aged , Neuropsychological Tests , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/psychology , Tumor Necrosis Factor-alphaABSTRACT
Multiple sclerosis is a chronic inflammatory and autoimmune disease of the central nervous system that affects more than 2.5 million people worldwide. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. Parthenolide, a natural sesquiterpene lactone found in Tanacetum parthenium L., is known for its strong anti-inflammatory activity. Herein, we have investigated the in vitro immunomodulatory effects of parthenolide on cytokine production and nitric oxide in cultured cells from myelin oligodendrocyte glycoprotein 35-55 amino acid peptide mice. Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide, and parthenolide was isolated from T. parthenium. Splenocytes and peritoneal cells were obtained from experimental autoimmune encephalomyelitis-induced mice and incubated with parthenolide (1, 5, and 20 µM). After in vitro treatment with parthenolide, supernatants were collected, and nitric oxide and cytokines were measured. The results suggested that parthenolide may regulate the activity of Th17 and Th1 cells, mainly by decreasing IL-17, TNF-α, and interferon gamma production. This modulation may be related to the lower levels of IL-12p40 and IL-6 after treatment with parthenolide. It was shown, for the first time, that parthenolide presents in vitro immunomodulatory effects on inflammatory mediators produced by cells from experimental autoimmune encephalomyelitis-induced mice.
