目的 探讨全血铜锌比值与维持性血液透析(maintenance hemodialysis,MHD)患者认知功能障碍(cognitive impairment,CI)的关系。 方法 选取2022年3月─2023年9月在徐州医科大学附属淮安医院行MHD治疗的130例患者作为研究对象,收集患者临床资料,根据蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)评分结果分为CI组(n=55)和认知功能正常组(n=75)。采用电感耦合等离子体质谱法检测患者全血锌、血铜水平。比较2组患者一般资料及实验室资料,分析铜锌比值与MoCA积分的相关性、MHD患者发生CI的独立影响因素以及铜锌比值对MHD患者CI的预测价值。 结果 CI组患者年龄(t=-6.161,P<0.001)、糖尿病占比(χ2=4.240,P=0.039)、透析龄(Z=-2.131,P=0.033)、超敏C反应蛋白(Z=-2.691,P=0.007)、全血铜(Z=-4.272,P<0.001)、铜锌比值(Z=-5.539,P<0.001)水平高于认知功能正常组,受教育年限(Z=-4.227,P<0.001)、肌酐(t=2.002,P=0.047)、血红蛋白(t=5.948,P<0.001)、白蛋白(Z=-5.519,P<0.001)、全血锌(t=4.872,P<0.001)水平低于认知功能正常组。Spearman相关性分析显示MoCA积分与全血铜锌比值呈负相关(r=-0.509,P<0.001)。多因素 Logistic回归分析结果显示铜锌比值(OR=1.449,95% CI:1.017~1.344,P=0.028)、年龄(OR =1.068,95% CI:1.002~1.138,P=0.044)是MHD患者CI的独立危险因素,白蛋白(OR=0.746,95%CI:0.616~0.904,P=0.003)、血红蛋白(OR=0.945,95% CI:0.906~0.987,P=0.011)是CI的独立保护因素。ROC曲线分析显示铜锌比值预测MHD患者发生CI的曲线下面积为0.785(95% CI:0.704~0.866,P<0.001),最佳截断值为0.15,此时敏感度和特异度分别为74.5%、76.0%。 结论 高全血铜锌比值是MHD患者发生CI的独立危险因素,对MHD患者合并CI有一定的预测价值。
Objective To explore the relationship between blood copper-zinc ratio and cognitive impairment (CI) in maintenance hemodialysis (MHD) patients. Methods A total of 130 MHD patients treated in the hemodialysis center of Huai'an Hospital Affiliated to Xuzhou Medical University between March 2022 and September 2023 were enrolled in this study. Their clinical data were collected. Based on the Montreal Cognitive Assessment (MoCA) score, the patients were divided into CI group (n=55) and normal cognitive group (n=75). Inductively coupled plasma mass spectrometry was used to measure blood zinc and copper levels. Baseline clinical and laboratory data were compared between the two groups. The correlation between copper-zinc ratio and MoCA score, the independent influence factors for the presence of CI, and the predictive value of copper-zinc ratio for CI in MHD patients were analyzed. Results Compared to the normal cognitive group, patients in the CI group had older age (t=-6.161, P<0.001), higher percentage of diabetics (c2=4.240, P=0.039), longer dialysis age (Z=-2.131, P=0.033), and higher levels of high sensitivity C-reactive protein (Z=-2.691, P=0.007), blood copper (Z=-4.272, P<0.001) and copper-zinc ratio (Z=-5.539, P<0.001), less years of education (Z=-4.227, P<0.001), and lower levels of creatinine (t=2.002, P=0.047), hemoglobin (t=5.948, P<0.001), albumin (Z=-5.519, P<0.001) and blood zinc (t=4.872, P<0.001). Spearman correlation analysis showed a negative correlation between MoCA score and the blood copper-zinc ratio (r=-0.509, P<0.001). Multivariate logistic regression analysis found that copper-zinc ratio (OR=1.449, 95% CI: 1.017~1.344) and age (OR=1.068, 95% CI: 1.002~1.138) were the independent risk factors for CI in MHD patients, while albumin (OR=0.746, 95% CI: 0.616~0.904) and hemoglobin (OR=0.945, 95% CI: 0.906~0.987) were the independent protective factors for CI (P<0.05). ROC curve analysis showed that the area under the curve of the copper-zinc ratio for predicting the presence of CI in MHD patients was 0.785 (95% CI: 0.704~0.866, P<0.001) and the optimal cut-off value was 0.15, at which the sensitivity and specificity were 74.5% and 76.0%, respectively. Conclusion Higher blood copper-zinc ratio is an independent risk factor for the development of CI in MHD patients. Blood copper-zinc ratio is useful for the prediction of CI in MHD patients.
[1] Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022 Apr;12(1):7-11. doi: 10.1016/j.kisu.2021.11.003.
[2] 喻倩,李寒,王世相.慢性肾脏病患者认知障碍研究进展[J].中国血液净化,2021,20(8):509-511.doi:10.3969/j.issn.1671-4091.2021.08.002.
[3] Miglinas M, Cesniene U, Janusaite MM, et al. Cerebrovascular Disease and Cog-nition in Chronic Kidney Disease Patients. Front Cardiovasc Med. 2020 Jun 3;7:96. doi: 10.3389/fcvm.2020.00096.
[4] Zhang YY, Li XS, Ren KD, et al. Restoration of metal homeostasis: a potential strategy against neurodegenerative diseases. Ageing Res Rev. 2023 Jun;87:101931. doi: 10.1016/j.arr.2023.101931.
[5] Shang N, Zhang L, Wang S, et al. Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an alumi-num factory in China: A cross-sectional study. Ecotoxicol Env-iron Saf. 2021 May;214:112110. doi: 10.1016/j.ecoenv.2021.112110.
[6] Yu J, He Y, Yu X, et al. Associations Between Mild Cognitive Impairment and Whole Blood Zinc and Selenium in the Elderly Cohort. Biol Trace Elem Res. 2023 Jan;201(1):51-64. doi: 10.1007/s12011-022-03136-3.
[7] Escobedo-Monge MF, Barrado E, Parodi-Román J, et al. Copper/Zinc Ratio in Childhood and Adolescence: A Review. Metabolites. 2023 Jan 3;13(1):82. doi: 10.3390/metabo13010082.
[8] Azevedo R, Gennaro D, Duro M, et al. Further Evidence on Trace Element Im-balances in Hemodialysis Patients-Paired Analysis of Blood and Serum Samples. Nutrients. 2023 Apr 15;15(8):1912. doi: 10.3390/nu15081912.
[9] Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assess-ment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
[10] Drew DA, Tighiouart H, Rollins J, et al. Evaluation of Screening Tests for Cogni-tive Impairment in Patients Receiving Maintenance Hemodialysis. J Am Soc Nephrol. 2020 Apr;31(4):855-864. doi: 10.1681/ASN.2019100988.
[11] Tian R, Guo Y, Ye P, et al. The validation of the Beijing version of the Montreal Cognitive Assessment in Chinese patients undergoing hemodialysis. PLoS One. 2020 Jan 9;15(1):e0227073. doi: 10.1371/journal.pone.0227073.
[12] Cao T, An R, Wang Y, et al. Risk factors and prevalence of cognitive impairment in maintenance hemodialysis patients: A systematic review and meta-analysis of observational studies. J Adv Nurs. 2023 Jun 26. doi: 10.1111/jan.15746.
[13] Pei X, Lai S, He X, et al. Mild cognitive impairment in maintenance hemodialysis patients: a cross-sectional survey and cohort study. Clin Interv Aging. 2018 Dec 20;14:27-32. doi: 10.2147/CIA.S178854.
[14] Pépin M, Klimkowicz-Mrowiec A, Godefroy O, et al. Cognitive disorders in pa-tients with chronic kidney disease: Approaches to prevention and treatment. Eur J Neurol. 2023 Sep;30(9):2899-2911. doi: 10.1111/ene.15928.
[15] Viggiano D, Wagner CA, Martino G, et al. Mechanisms of cognitive dysfunction in CKD. Nat Rev Nephrol. 2020 Aug;16(8):452-469. doi: 10.1038/s41581-020-0266-9.
[16] Liu Y, Tang R, Xu Q, et al. High Blood Cu/Zn Ratio is Associated with Nutrition-al Risk in Patients Undergoing Maintenance Hemodialysis. Biol Trace Elem Res. 2022 Dec;200(12):4977-4987. doi: 10.1007/s12011-022-03104-x.
[17] Malavolta M, Piacenza F, Basso A, et al. Serum copper to zinc ratio: Relationship with aging and health status. Mech Ageing Dev. 2015 Nov;151:93-100. doi: 10.1016/j.mad.2015.01.004.
[18] Xie Z, Tong S, Chu X, et al. Chronic Kidney Disease and Cognitive Impairment: The Kidney-Brain Axis. Kidney Dis (Basel). 2022 May 3;8(4):275-285. doi: 10.1159/000524475.
[19] Prasad AS, Bao B. Molecular Mechanisms of Zinc as a Pro-Antioxidant Mediator: Clinical Therapeutic Implications. Antioxidants (Basel). 2019 Jun 6;8(6):164. doi: 10.3390/antiox8060164.
[20] Sun R, Wang J, Feng J, et al. Zinc in Cognitive Impairment and Aging. Biomole-cules. 2022 Jul 18;12(7):1000. doi: 10.3390/biom12071000.
[21] Scolari Grotto F, Glaser V. Are high copper levels related to Alzheimer's and Parkinson's diseases? A systematic review and meta-analysis of articles published between 2011 and 2022.Biometals.2023 Aug 18. doi: 10.1007/s10534-023-00530-9.
[22] Hsu HW, Bondy SC, Kitazawa M. Environmental and Dietary Exposure to Cop-per and Its Cellular Mechanisms Linking to Alzheimer's Disease. Toxi-col Sci. 2018 Jun 1;163(2):338-345. doi: 10.1093/toxsci/kfy025.
[23] Gromadzka G, Tarnacka B, Flaga A, et al. Copper Dyshomeostasis in Neu-rodegenerative Diseases Therapeutic Implications. Int J Mol Sci. 2020 Dec 4;21(23):9259. doi: 10.3390/ijms21239259.
[24] Zuo S, Liu M, Liu Y, et al. Association Between the Blood Copper-Zinc (Cu/Zn) Ratio and Anemia in Patients Undergoing Maintenance Hemodialysis. Biol Trace Elem Res. 2022 Jun;200(6):2629-2638. doi: 10.1007/s12011-021-02888-8.
[25] Qiang YX, Deng YT, Zhang YR, et al. Associations of blood cell indices and anemia with risk of incident dementia: A prospective cohort study of 313,448 participants.Alzheimers Dement. 2023 Sep;19(9):3965-3976. doi: 10.1002/alz.13088.