阿尔茨海默病、血管性痴呆和轻度认知障碍患者认知功能下降与促炎细胞因子水平的关系

O. Chyniak, O. Dubenko, Olexander Potapov
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A significant positive correlation was established between IL-23 and individual sections of the ADAS-cog scale in patients with MCD (r = 0.423; p = 0.020), namely with «word recognition tasks» (r = 0.466; p = 0.030), «understanding» (r = 0.306; p = 0.059) as well as «strike out numbers» (r = 0.301; p = 0.061). A weak positive correlation was found between the serum concentration of IL-23 and ADAS-cog scores in patients with VD (r = 0.497; p = 0.045). Moderate positive correlation was observed for IL-23 with «concentration and distraction» (r = 0.558; p = 0.040). An inverse correlation was established between the serum levels of IL-23 and MoCA scores in patients with VD (r = −0.510; р = 0.060), especially with «language» (r = −0.538; p = 0.047) and «executive functioning» (r = −0.485; p = 0.079). However, no other significant correlations were found between the serum concentration of IL-17 and neurocognitive domains in patients with MCD and VD.\nCorrelation analysis confirmed the relationship between the severity of cognitive impairment and the level of proinflammatory markers, suggesting that inflammation can lead to cognitive decline in AD patients. The results of the study indicated that IL-23 may have a more complex relationship with the progression of this disease which gives reason to consider IL-23 as a marker of inflammatory activity.\nLevels of detectable proinflammatory cytokines (IL-17 and IL-23) were significantly higher in patients with AD vs. patients with VD and MCD. Such more pronounced changes in the production of interleukin 23 in patients with AD may indicate the activity of the inflammatory process. The level of IL-23 in all examined patients with Alzheimer's disease had high correlations with indicators of neurocognitive scales, which indicated its important role in the pathogenesis of this disease. There were no other significant correlations between the serum concentration of IL-17 and neurocognitive domains in patients with MCD and VD.","PeriodicalId":315243,"journal":{"name":"Eastern Ukrainian Medical Journal","volume":"75 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"THE RELATIONSHIP BETWEEN DECREASED COGNITIVE FUNCTIONS AND THE LEVEL OF PROINFLAMMATORY CYTOKINES IN PATIENTS WITH ALZHEIMER’S DISEASE, VASCULAR DEMENTIA, AND MILD COGNITIVE DISORDER\",\"authors\":\"O. Chyniak, O. 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引用次数: 1

摘要

阿尔茨海默病(Alzheimer's disease, AD)是一种导致痴呆症状的退行性疾病[1,2]。阿尔茨海默病的组织病理学征象是大脑中的淀粉样斑块,主要由淀粉样β-肽-40 (Aβ-40)和淀粉样β-肽-42 (Aβ-42)的纤维状形式组成。中性粒细胞是IL-17在中枢神经系统(CNS)中的主要靶点,可促进中枢神经系统组织的炎症和损伤,可能在AD病理发展中发挥重要作用。白细胞介素23 (IL - 23)与IL-6、IL-1协同作用,参与促炎背景下Th17细胞的分化。本研究旨在分析AD、血管性痴呆(VD)和轻度认知障碍(MCD)患者白细胞介素IL-17、IL-23水平与神经认知量表的关系。研究共纳入89例患者,其中59例患者存在认知功能障碍(男性32例,女性27例,平均年龄66.8±8.4岁);其中,重度神经认知障碍(NCD)患者29例,其中AD患者15例,VD患者14例,MCD患者30例,对照组30例无认知障碍。所有患者均采用以下测试和量表进行综合神经心理检查:迷你精神状态检查(MMSE)、蒙特利尔认知评估(MoCA)、额叶评估组(FAB)、阿尔茨海默病认知评估量表(ADAScog)。采用夹心ELISA法检测血清中IL-17和IL-23细胞因子的水平,ELISA采用«Chem Well 2900»免疫分析仪(Awareness Technology, USA)。测试系统使用Bender Medsystems, Australia (IL-17和IL-23),按照制造商的说明使用。AD患者检测到的白细胞介素(IL-17和IL-23)水平明显高于VD和MCD患者。检测两种细胞因子与MMSE量表、MoCA、ADAS-cog和FAB的相关性。我们的研究结果显示,所有AD患者血清IL-23浓度与神经认知量表之间存在显著正相关。AD组中最相关的相关性与量表相关:ADAS-cog (r = 0.760;r = 0.001),即“重复单词的任务”部分(r = 0.775;P小于0.001),"建设性实践" (r = 0.651;P = 0.010),«取向»(r = 0.684;P = 0.01),以及«单词识别任务»(r = 0.616;P = 0.020);和MoCA量表(r =−0.592;P = 0.020),即“延迟召回”部分(r = - 0.641;P = 0.010)。MCD患者IL-23与ADAS-cog量表各部分呈显著正相关(r = 0.423;P = 0.020),即“单词识别任务”(r = 0.466;P = 0.030),“理解”(r = 0.306;P = 0.059)以及“三振数”(r = 0.301;P = 0.061)。VD患者血清IL-23浓度与ADAS-cog评分呈弱正相关(r = 0.497;P = 0.045)。IL-23与“注意力分散”呈中度正相关(r = 0.558;P = 0.040)。VD患者血清IL-23水平与MoCA评分呈负相关(r = - 0.510;r = 0.060),尤其是«language»(r =−0.538;P = 0.047)和“执行功能”(r = - 0.485;P = 0.079)。然而,MCD和VD患者血清IL-17浓度与神经认知域之间未发现其他显著相关性。相关分析证实了认知障碍严重程度与促炎标志物水平之间的关系,提示炎症可导致AD患者认知能力下降。研究结果表明,IL-23可能与该疾病的进展有更复杂的关系,因此有理由认为IL-23是炎症活性的标志。AD患者检测到的促炎细胞因子(IL-17和IL-23)水平明显高于VD和MCD患者。AD患者白细胞介素23产生的这种更明显的变化可能表明炎症过程的活性。IL-23在所有被检查的阿尔茨海默病患者中水平与神经认知量表指标高度相关,提示其在阿尔茨海默病发病机制中的重要作用。MCD和VD患者血清IL-17浓度与神经认知域之间无其他显著相关性。
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THE RELATIONSHIP BETWEEN DECREASED COGNITIVE FUNCTIONS AND THE LEVEL OF PROINFLAMMATORY CYTOKINES IN PATIENTS WITH ALZHEIMER’S DISEASE, VASCULAR DEMENTIA, AND MILD COGNITIVE DISORDER
Alzheimer's disease (AD) is a degenerative disease that leads to dementia symptoms [1, 2]. Histopathological signs of AD are amyloid plaques in the brain, mainly consisting of fibrillary forms of amyloid β-peptide-40 (Aβ-40) and amyloid β-peptide-42 (Aβ-42). Neutrophils are the main targets for IL-17 in the central nervous system (CNS) that promote inflammation and damage to CNS tissues, and may play an important role in the development of AD pathology. Interleukin 23 (IL‑23) synergizes with IL-6, IL-1 and is involved in the differentiation of Th17 cells in a pro-inflammatory context. The aim of the study was to analyze the relationship between interleukin levels of IL-17, IL-23 and neurocognitive scales in patients with AD, vascular dementia (VD) and mild cognitive disorder (MCD). The study involved 89 patients, of which 59 patients had cognitive impairment (32 men and 27 women, mean age 66.8±8.4 years); among them, 29 had major neurocognitive impairment (NCD), including 15 patients with AD, 14 – with VD, 30 patients – with MCD and 30 people in the control group had no cognitive deficit. All patients were tested with comprehensive neuropsychological examination using the following tests and scales: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Alzheimer Disease Assessment Scale-cognitive (ADAScog). Serum levels of cytokines of IL-17 and IL-23 were assayed using sandwich ELISA on «Chem Well 2900» immunoanalyzer (Awareness Technology, USA). Test systems using Bender Medsystems, Australia (IL-17 and IL-23) were used in accordance with the manufactures instructions. Levels of detectable interleukins (IL-17 and IL-23) were significantly higher in patients with AD vs. patients with VD and MCD. The correlations between the two cytokines and the MMSE scales, MoCA, ADAS-cog and FAB were examined. Our results showed a significant positive correlation between the serum concentration of IL-23 and neurocognitive scales in all patients with AD. The most relevant correlations in the AD group were linked with the scales: ADAS-cog (r = 0.760; р = 0.001), namely with the sections «tasks for repeating words» (r = 0.775; p ˂ 0.001), «constructive praxis» (r = 0.651; p = 0.010), «orientation» (r = 0.684; p = 0.01), as well as «word recognition tasks» (r = 0.616; p = 0.020); and with MoCA scale (r = −0.592; p = 0.020), namely with the section «delayed recall» (r = −0.641; p = 0.010). A significant positive correlation was established between IL-23 and individual sections of the ADAS-cog scale in patients with MCD (r = 0.423; p = 0.020), namely with «word recognition tasks» (r = 0.466; p = 0.030), «understanding» (r = 0.306; p = 0.059) as well as «strike out numbers» (r = 0.301; p = 0.061). A weak positive correlation was found between the serum concentration of IL-23 and ADAS-cog scores in patients with VD (r = 0.497; p = 0.045). Moderate positive correlation was observed for IL-23 with «concentration and distraction» (r = 0.558; p = 0.040). An inverse correlation was established between the serum levels of IL-23 and MoCA scores in patients with VD (r = −0.510; р = 0.060), especially with «language» (r = −0.538; p = 0.047) and «executive functioning» (r = −0.485; p = 0.079). However, no other significant correlations were found between the serum concentration of IL-17 and neurocognitive domains in patients with MCD and VD. Correlation analysis confirmed the relationship between the severity of cognitive impairment and the level of proinflammatory markers, suggesting that inflammation can lead to cognitive decline in AD patients. The results of the study indicated that IL-23 may have a more complex relationship with the progression of this disease which gives reason to consider IL-23 as a marker of inflammatory activity. Levels of detectable proinflammatory cytokines (IL-17 and IL-23) were significantly higher in patients with AD vs. patients with VD and MCD. Such more pronounced changes in the production of interleukin 23 in patients with AD may indicate the activity of the inflammatory process. The level of IL-23 in all examined patients with Alzheimer's disease had high correlations with indicators of neurocognitive scales, which indicated its important role in the pathogenesis of this disease. There were no other significant correlations between the serum concentration of IL-17 and neurocognitive domains in patients with MCD and VD.
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