老年人血浆IL-6、TNF-α水平与轻度认知功能障碍的关联

吴茵如; 钟逸诗; 高健; 陈沛良; 由芳菲; 宋玮琦; 毛琛

doi:10.16462/j.cnki.zhjbkz.2024.03.020

老年人血浆IL-6、TNF-α水平与轻度认知功能障碍的关联

doi: 10.16462/j.cnki.zhjbkz.2024.03.020

南方医科大学公共卫生学院流行病学系，广州 510515

基金项目:

国家自然科学基金 81973109

详细信息

通讯作者:
毛琛，E-mail：maochen9@smu.edu.cn

中图分类号: R749.1+6
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出版历程
- 收稿日期: 2023-08-29
- 修回日期: 2024-01-10
- 网络出版日期: 2024-04-08
- 刊出日期: 2024-03-10

Association between plasma levels of IL-6 and TNF-α and mild cognitive impairment in the elderly

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou 510515, China

Funds:

National Natural Science Foundation of China 81973109

More Information

Corresponding author: MAO Chen, E-mail: maochen9@smu.edu.cn

摘要

摘要: 目的分析广东老年人(≥65岁)血浆白细胞介素-6(interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平与轻度认知功能障碍(mild cognitive impairment, MCI)的关联。方法选取广东某社区卫生服务中心就诊的48例老年MCI患者作为病例组，96例无MCI的老年人作为对照组。采用logistic回归分析血浆IL-6、TNF-α水平与MCI的关联。绘制受试者工作特征(receiver operating characteristic, ROC)曲线评估血浆IL-6、TNF-α水平对MCI的诊断价值。结果共纳入144名老年人，其中48名MCI患者，63名男性(43.8%)。多因素logistic回归分析结果显示，血浆IL-6、TNF-α水平升高可使MCI患病风险增加，血浆IL-6、TNF-α水平每增高1个s，MCI患病风险分别增加53%和51%(OR=1.53, 95% CI: 1.02~2.29, P=0.040; OR=1.51, 95% CI: 1.04~2.20, P=0.029)。血浆IL-6、TNF-α的ROC曲线下面积分别为0.60、0.64。结论血浆IL-6和TNF-α水平升高可能与≥65岁老年人MCI患病风险的增加有关。
- 老年人 /
- 轻度认知功能障碍 /
- 白细胞介素-6 /
- 肿瘤坏死因子-α /
- 病例对照研究
Abstract: Objective To analyze the association between plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and mild cognitive impairment (MCI) in elderly individuals aged 65 years and older in Guangdong. Methods A total of 48 MCI elderly patients who visited a community health service center in Guangdong were selected as the case group, while 96 non-MCI individuals served as controls. Logistic regression models were used to analyze the association between plasma levels of IL-6 and TNF-α and MCI. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of plasma levels of IL-6 and TNF-α for MCI. Results A total of 144 elderly individuals were enrolled, including 48 MCI patients and 63 males (43.8%). The results of the multivariate logistic regression models showed that increased plasma levels of IL-6 and TNF-α could lead to a higher risk of MCI. Specifically, the risk of MCI increased by 53% and 51% for each standard deviation increase in plasma levels of IL-6 and TNF-α, respectively (OR=1.53, 95% CI: 1.02-2.29, P=0.040; OR=1.51, 95% CI: 1.04-2.20, P=0.029). The areas under the ROC curves for IL-6 and TNF-α were 0.60 and 0.64, respectively. Conclusions The increased risk of MCI in individuals aged 65 years and older may be associated with elevated plasma levels of IL-6 and TNF-α.
- Elderly /
- Mild cognitive impairment /
- Interleukin-6 /
- Tumor necrosis factor-α /
- Case-control study

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图 1 血浆IL-6、TNF-α水平诊断MCI的ROC曲线

Figure 1. ROC curve of plasma levels of IL-6 and TNF-α for the diagnosis of MCI

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表 1 研究对象基本特征

Table 1. Basic characteristics of the study subjects

变量Variable	总人数 ^①Total ^①(n=144)	对照组 ^①Control group ^①(n=96)	MCI组 ^①group ^①(n=48)	χ²/Z值value	P值value
年龄/岁Age/years	72.0(69.0, 80.0)	72.5(69.0, 80.8)	71.5(69.0, 80.0)	-0.117	0.907
性别Gender				0.001	0.999
男Male	63(43.8)	42(43.8)	21(43.8)
女Female	81(56.2)	54(56.2)	27(56.2)
婚姻状况Marital status				0.077	0.781
在婚Married	110(76.4)	74(77.1)	36(75.0)
其他Other	34(23.6)	22(22.9)	12(25.0)
吸烟Smoking				0.054	0.817
否No	134(93.1)	89(92.7)	45(93.8)
是Yes	10(6.9)	7(7.3)	3(6.2)
饮酒Drinking				0.030	0.862
否No	125(86.8)	83(86.5)	42(87.5)
是Yes	19(13.2)	13(13.5)	6(12.5)
锻炼情况Exercise status				0.286	0.593
是Yes	126(87.5)	85(88.5)	41(85.4)
否No	18(12.5)	11(11.5)	7(14.6)
高血压Hypertension				0.694	0.405
否No	62(43.1)	39(40.6)	23(47.9)
是Yes	82(56.9)	57(59.4)	25(52.1)
糖尿病Diabetes				0.758	0.384
否No	114(79.2)	74(77.1)	40(83.3)
是Yes	30(20.8)	22(22.9)	8(16.7)
冠状动脉粥样硬化Coronary heart disease				2.133	0.144
否No	135(93.8)	88(91.7)	47(97.9)
是Yes	9(6.2)	8(8.3)	1(2.1)
脑血管病Cerebrovascular disease				0.414	0.520
否No	139(96.5)	92(95.8)	47(97.9)
是Yes	5(3.5)	4(4.2)	1(2.1)
关节炎Arthritis				2.532	0.112
否No	130(90.3)	84(87.5)	46(95.8)
是Yes	14(9.7)	12(12.5)	2(4.2)
IL-6/(ng·L^-1)	13.87(11.05, 17.92)	13.41(9.80, 17.67)	14.93(11.96, 19.89)	-1.973	0.049
TNF-α/(ng·L^-1)	302.78(195.19, 393.37)	265.42(190.71, 374.09)	375.80(236.85, 432.99)	-2.712	0.007
注：①以人数(占比/%)或M(P₂₅，P₇₅)表示。 Note: ① Number of people (proportion/%) or M(P₂₅，P₇₅).

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表 2 血浆IL-6、TNF-α水平与MCI的关联

Table 2. Association between IL-6, TNF-α and MCI

变量Variable	人数Number of people	模型1 Model 1		模型2 Model 2		模型3 Model 3
变量Variable	人数Number of people	OR值value(95% CI)	P值value	OR值value(95% CI)	P值value	OR值value(95% CI)	P值value
IL-6/(ng·L^-1)	144	1.43(0.99~2.07)	0.054	1.50(1.02~2.18)	0.039	1.53(1.02~2.29)	0.040
＜11.10	36	1.00		1.00		1.00
11.10~＜13.90	36	3.24(1.07~9.83)	0.038	3.22(1.04~9.97)	0.042	3.53(1.11~11.21)	0.032
13.90~＜17.90	36	3.30(1.07~10.14)	0.037	3.51(1.09~11.34)	0.036	3.37(1.02~11.17)	0.047
≥17.90	36	3.24(1.07~9.83)	0.038	3.54(1.13~11.03)	0.030	4.14(1.28~13.40)	0.018
P_trend			0.059		0.045		0.032
TNF-α/(ng·L^-1)	144	1.43(1.01~2.04)	0.047	1.51(1.05~2.17)	0.025	1.51(1.04~2.20)	0.029
＜194.20	36	1.00		1.00		1.00
194.20~＜297.20	36	0.72(0.23~2.22)	0.566	0.75(0.24~2.36)	0.627	0.68(0.21~2.18)	0.519
297.20~＜391.88	36	2.13(0.77~5.91)	0.145	2.45(0.85~7.03)	0.096	2.26(0.76~6.70)	0.142
≥391.88	36	2.67(0.98~7.28)	0.055	2.99(1.07~8.34)	0.037	3.13(1.09~8.97)	0.034
P_trend			0.013		0.008		0.008
注：模型1，调整年龄、性别；模型2，在模型1的基础上进一步调整婚姻状况、吸烟、饮酒、锻炼；模型3，在模型2的基础上进一步调整高血压、糖尿病、冠状动脉粥样硬化、脑血管病及关节炎患病情况。 Notes: Model 1, adjusting for age, gender; Model 2, on the basis of model 1, marital status, smoking, drinking, exercise were adjusted; Model 3, on the basis of model 2, hypertension, diabetes, coronary heart disease, cerebrovascular disease, arthritis were adjusted.

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表 3 血浆IL-6、TNF-α水平对MCI的诊断价值

Table 3. Diagnostic value of plasma levels of IL-6 and TNF-α for MCI

变量Variable	AUC	95% CI	P值value	诊断临界值/(ng·L^-1)Cut-off point/(ng·L^-1)	约登指数Youden index	灵敏度/%Sensitivity/%	特异度/%Specificity/%
IL-6/(ng·L^-1)	0.60	0.51~0.69	0.049	11.31	0.24	87.50	36.50
TNF-α/(ng·L^-1)	0.64	0.54~0.74	0.007	353.86	0.32	62.50	69.80

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参考文献(13)

[1]	Anderson ND. State of the science on mild cognitive impairment (MCI)[J]. CNS Spectr, 2019, 24(1): 78-87. DOI: 10.1017/s1092852918001347.
[2]	Kasper S, Bancher C, Eckert A, et al. Management of mild cognitive impairment (MCI): the need for national and international guidelines[J]. World J Biol Psychiatry, 2020, 21(8): 579-594. DOI: 10.1080/15622975.2019.1696473.
[3]	Ghanbari M, Li G, Hsu LM, et al. Accumulation of network redundancy marks the early stage of Alzheimer's disease[J]. Hum Brain Mapp, 2023, 44(8): 2993-3006. DOI: 10.1002/hbm.26257.
[4]	Shen XN, Niu LD, Wang YJ, et al. Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies[J]. J Neurol Neurosurg Psychiatry, 2019, 90(5): 590-598. DOI: 10.1136/jnnp-2018-319148.
[5]	Swardfager W, Lanctôt K, Rothenburg L, et al. A meta-analysis of cytokines in Alzheimer's disease[J]. Biol Psychiatry, 2010, 68(10): 930-941. DOI: 10.1016/j.biopsych.2010.06.012.
[6]	Chi GC, Fitzpatrick AL, Sharma M, et al. Inflammatory biomarkers predict domain-specific cognitive decline in older adults[J]. J Gerontol A Biol Sci Med Sci, 2017, 72(6): 796-803. DOI: 10.1093/gerona/glw155.
[7]	Capogna E, Watne LO, Sørensen Ø, et al. Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers - in cognitively unimpaired older adults[J]. Brain Behav Immun, 2023, 113: 56-65. DOI: 10.1016/j.bbi.2023.06.027.
[8]	Julian A, Dugast E, Ragot S, et al. There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer's disease[J]. Aging Clin Exp Res, 2015, 27(5): 589-594. DOI: 10.1007/s40520-015-0332-5.
[9]	中华医学会神经病学分会痴呆与认知障碍学组. 阿尔茨海默病源性轻度认知障碍诊疗中国专家共识2021[J]. 中华神经科杂志, 2022, 55(5): 421-440. DOI: 10.3760/cma.j.cn113694-20211004-00679. Chinese Society of Dementia and Cognitive Impairment. Chinese expert consensus on the diagnosis and treatment of mild cognitive impairment due to Alzheimer's disease 2021[J]. Chin J Neurol, 2022, 55(5): 421-440. DOI: 10.3760/cma.j.cn113694-20211004-00679.
[10]	Boccardi V, Paolacci L, Remondini D, et al. Cognitive decline and Alzheimer's disease in old age: a sex-specific cytokinome signature[J]. J Alzheimers Dis, 2019, 72(3): 911-918. DOI: 10.3233/jad-190480.
[11]	Huang Z, Wong LW, Su Y, et al. Blood-brain barrier integrity in the pathogenesis of Alzheimer's disease[J]. Front Neuroendocrinol, 2020, 59: 100857. DOI: 10.1016/j.yfrne.2020.100857.
[12]	Rajesh Y, Kanneganti TD. Innate immune cell death in neuroinflammation and Alzheimer's disease[J]. Cells, 2022, 11(12): 1885. DOI: 10.3390/cells11121885.
[13]	López-Ornelas A, Jiménez A, Pérez-Sánchez G, et al. The impairment of blood-brain barrier in Alzheimer's disease: challenges and opportunities with stem cells[J]. Int J Mol Sci, 2022, 23(17): 10136. DOI: 10.3390/ijms231710136.