Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (10): 106-114.doi: 10.6040/j.issn.1671-7554.0.2024.0647

• Clinical Medicine • Previous Articles    

Therapeutic efficacy of idebenone on cognitive impairment in patients with Parkinsons disease

REN Yanhong, LI Xiuhua, ZHU Xiaoran, FANG Yuqing, ZHAO Zhangning, MAO Fei, WANG Yalin, ZHANG Yanqing, LIU Tianhao, XU Xinrong   

  1. Department of Neurology, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan 250014, Shandong, China
  • Published:2024-10-12

PDF (PC)

610

Abstract: Objective To investigate the therapeutic effects of idebenone in patients with Parkinsons disease-related cognitive impairment and to explore its mechanisms of action. Methods A total of 216 patients with Parkinsons disease-related cognitive impairment who were hospitalized in the The First Affiliated Hospital of Shandong First Medical University from January 2017 to January 2024 were included. The patients were randomly divided into the conventional treatment group(n=82)and the idebenone treatment group(n=134). The changes of the Montreal Cognitive Assessment(MoCA)and its subdomain cognitive scores, the Mini-Mental State Examination(MMSE), the Unified Parkinsons Disease Rating Scale Ⅲ(UPDRS-Ⅲ), the Cholinergic Pathways Hyperintensities Score(CHIPS), interleukin-6(IL-6), peripheral blood superoxide dismutase(SOD), liver function, and kidney function were monitored for both groups before drug treatment and after 12 months of continuous drug treatment. Results There were no statistically significant differences in general data, Hoehn-Yahr(H-Y)staging, various scale scores and hematological indicators before treatment(P>0.05). After 12 months of drug treatment, the increase in MoCA scores and their single-domain visuospatial executive ability and language was higher in the idebenone treatment group than in the conventional treatment group(P<0.05), and the decrease in UPDRS-Ⅲ scores was even more pronounced(P<0.05). The IL-6 levels in the idebenone treatment group decreased, while those in the conventional treatment group increased, with a statistically significant difference between the two groups(P<0.05). The SOD levels in the idebenone treatment group increased, while those in the conventional treatment group decreased, with a statistically significant difference between the two groups(P<0.05). There were no statistically significant differences in liver and kidney function-related indicators between the two groups(P>0.05). After adjusting for pre-treatment CHIPS scores, disease duration, and age covariates, the CHIPS score in the idebenone treatment group was 2.19 points lower than that in the conventional treatment group(F=229.16, P<0.01, R2=0.91, adjusted R2=0.90). Conclusion Idebenone can significantly alleviate cognitive impairment, improve motor symptoms, delay the damage of white matter hyperintensities to the cholinergic pathways, increase peripheral blood SOD levels, and reduce IL-6 levels in patients with Parkinsons disease.

Key words: Parkinsons disease, Cognitive impairment, Idebenone, Motor symptoms, Cholinergic Pathways Hyperintensities Score

CLC Number: 

  • R741
[1] Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment[J]. Nat Rev Dis Primers, 2021, 7(1): 47.
[2] Bäckström D, Granåsen G, Domellöf ME, et al. Early predictors of mortality in Parkinsonism and Parkinson disease: a population-based study[J]. Neurology, 2018, 91(22): e2045-e2056.
[3] Han JJ, Fan YH, Wu PP, et al. Parkinsons disease dementia: synergistic effects of alpha-synuclein, tau, beta-amyloid, and iron[J]. Front Aging Neurosci, 2021, 13: 743754. doi:10.3389/fnagi.2021.743754.
[4] Degirmenci Y, Angelopoulou E, Georgakopoulou VE, et al. Cognitive impairment in Parkinsons disease: an updated overview focusing on emerging pharmaceutical treatment approaches[J]. Medicina, 2023, 59(10): 1756.
[5] Gueven N, Ravishankar P, Eri R, et al. Idebenone: when an antioxidant is not an antioxidant[J]. Redox Biol, 2021, 38: 101812. doi:10.1016/j.redox.2020.101812.
[6] Jaber S, Polster BM. Idebenone and neuroprotection: antioxidant, pro-oxidant, or electron carrier?[J]. J Bioenerg Biomembr, 2015, 47(1/2): 111-118.
[7] Yan JQ, Sun WJ, Shen MM, et al. Idebenone improves motor dysfunction, learning and memory by regulating mitophagy in MPTP-treated mice[J]. Cell Death Discov, 2022, 8(1): 28.
[8] He PK, Gao YY, Lyu FJ, et al. Idebenone-activating autophagic degradation of α-synuclein via inhibition of AKT-mTOR pathway in a SH-SY5Y-A53T model of Parkinsons disease: a network pharmacological approach[J]. Evid Based Complement Alternat Med, 2021, 2021: 8548380. doi:10.1155/2021/8548380.
[9] Bocti C, Swartz RH, Gao FQ, et al. A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia[J]. Stroke, 2005, 36(10): 2126-2131.
[10] Garcia-Ptacek S, Kramberger MG. Parkinson disease and dementia[J]. J Geriatr Psychiatry Neurol, 2016, 29(5): 261-270.
[11] Smith C, Malek N, Grosset K, et al. Neuropathology of dementia in patients with Parkinsons disease: a systematic review of autopsy studies[J]. J Neurol Neurosurg Psychiatry, 2019, 90(11): 1234-1243.
[12] Aarsland D, Creese B, Politis M, et al. Cognitive decline in Parkinson disease[J]. Nat Rev Neurol, 2017, 13(4): 217-231.
[13] Giorgio V, Petronilli V, Ghelli A, et al. The effects of idebenone on mitochondrial bioenergetics[J]. Biochim Biophys Acta, 2012, 1817(2): 363-369.
[14] Rauchová H. Coenzyme Q10 effects in neurological diseases[J]. Physiol Res, 2021, 70(l4): S683-S714.
[15] Cardoso SM, Pereira C, Oliveira CR. The protective effect of vitamin E, idebenone and reduced glutathione on free radical mediated injury in rat brain synaptosomes[J]. Biochem Biophys Res Commun, 1998, 246(3): 703-710.
[16] Lee HJ, Park JH, Hoe HS. Idebenone regulates aβ and LPS-induced neurogliosis and cognitive function through inhibition of NLRP3 inflammasome/IL-1β axis activation[J]. Front Immunol, 2022, 13: 749336. doi:10.3389/fimmu.2022.749336.
[17] 黄骥, 阳军, 欧阳娟, 等. 艾地苯醌联合多巴丝肼治疗帕金森病的临床研究[J]. 药物评价研究, 2020, 43(12): 2501-2504. HUANG Ji, YANG Jun, OUYANG Juan, et al. Clinical study on idebenone combined levodopa and benserazide hydrochloride in treatment of Parkinsons disease[J]. Drug Evaluation Research, 2020, 43(12): 2501-2504.
[18] 夏秋怡, 徐茂青, 霍青.艾地苯醌结合美多芭对帕金森患者的疗效、步态及精神状态的影响[J]. 卒中与神经疾病, 2020, 27(5): 627-630. XIA Qiuyi, XU Maoqing, HUO Qing, et al. The effects of idebenone combined with madopar on the efficacy, gait, and mental state of patients with parkinsons disease[J]. Stroke and Nervous Diseases, 2020, 27(5): 627-630.
[19] 赵海龙, 王皓, 方雨晴, 等. 增服艾地苯醌对34例帕金森病抑郁患者的疗效观察[J]. 山东大学学报(医学版), 2022, 60(4): 38-44. ZHAO Hailong, WANG Hao, FANG Yuqing, et al. Efficacy of additional idebenone in the treatment of 34 patients with Parkinsons disease with depression[J]. Journal of Shandong University(Health Sciences), 2022, 60(4): 38-44.
[20] 马秀娟, 朱宁, 朱洪山, 等. 艾地苯醌治疗帕金森病轻度认知障碍的临床疗效观察[J]. 世界最新医学信息文摘(连续型电子期刊), 2020, 20(16): 138-139, 141. MA Xiujuan, ZHU Ning, ZHU Hongshan, et al. Clinical effect of idebenone on mild cognitive impairment of Parkinsons disease[J]. World Latest Medicine Information(Continuous Electronic Journal), 2020, 20(16): 138-139, 141.
[21] Carbon M, Ma YL, Barnes A, et al. Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism[J]. Neuroimage, 2004, 21(4): 1497-1507.
[22] Gatt AP, Duncan OF, Attems J, et al. Dementia in Parkinsons disease is associated with enhanced mitochondrial complex I deficiency[J]. Mov Disord, 2016, 31(3): 352-359.
[23] Lizama BN, Chu CT. Neuronal autophagy and mitophagy in Parkinsons disease[J]. Mol Aspects Med, 2021, 82: 100972. doi:10.1016/j.mam.2021.100972.
[24] 闫俊强, 刘安然, 黄家瑞, 等. 艾地苯醌对帕金森病模型小鼠行为学及脑组织线粒体自噬水平的影响[J]. 中华行为医学与脑科学杂志, 2021, 30(1): 15-21. YAN Junqiang, LIU Anran, HUANG Jiarui, et al. Effects of idebenone on behavior and mitochondrial autophagy of brain tissue in Parkinson disease model mice[J]. Chinese Journal of Behavioral Medicine and Brain Science, 2021, 30(1): 15-21.
[25] Liu H, Deng B, Xie F, et al. The influence of white matter hyperintensity on cognitive impairment in Parkinsons disease[J]. Ann Clin Transl Neurol, 2021, 8(9): 1917-1934.
[26] Shin J, Choi S, Lee JE, et al. Subcortical white matter hyperintensities within the cholinergic pathways of Parkinsons disease patients according to cognitive status[J]. J Neurol Neurosurg Psychiatry, 2012, 83(3): 315-321.
[27] Qi XM, Tang HD, Luo Q, et al. White matter hyperintensities predict cognitive decline: a community-based study[J]. Can J Neurol Sci, 2019, 46(4): 383-388.
[28] 张晓韬, 何天齐, 朱梅佳, 等.艾地苯醌联合治疗帕金森病疗效的临床观察[J].山东大学学报(医学版), 2019, 57(4): 34-41. ZHANG Xiaotao, HE Tianqi, ZHU Meijia, et al. Clinical observation of the effects of idebenone on Parkinsons disease[J]. Journal of Shandong University(Health Sciences), 2019, 57(4): 34-41.
[29] Dionísio PA, Amaral JD, Rodrigues CMP. Oxidative stress and regulated cell death in Parkinsons disease[J]. Ageing Res Rev, 2021, 67: 101263. doi:10.1016/j.arr.2021.101263.
[30] Pajares M, I Rojo A, Manda G, et al. Inflammation in Parkinsons disease: mechanisms and therapeutic implications[J]. Cells, 2020, 9(7): 1687.
[31] 刘震宇, 姚淑芳. 艾地苯醌联合多巴丝肼对帕金森患者血清SOD、MDA、8-OHdG水平的影响[J]. 现代诊断与治疗, 2021, 32(9): 1375-1377. LIU Zhenyu, YAO Shufang. Effects of idebenone combined with dobutamine on serum SOD, MDA and 8-OHdG levels in patients with Parkinsons disease[J]. Modern Diagnosis and Treatment, 2021, 32(9): 1375-1377.
[32] Avcı B, Günaydın C, Güvenç T, et al. Idebenone ameliorates rotenone-induced Parkinsons disease in rats through decreasing lipid peroxidation[J]. Neurochem Res, 2021, 46(3): 513-522.
[33] Tansey MG, Romero-Ramos M. Immune system responses in Parkinsons disease: early and dynamic[J]. Eur J Neurosci, 2019, 49(3): 364-383.
[34] Yan AJ, Liu ZH, Song L, et al. Idebenone alleviates neuroinflammation and modulates microglial polarization in LPS-stimulated BV2 cells and MPTP-induced Parkinsons disease mice[J]. Front Cell Neurosci, 2018, 12: 529. doi:10.3389/fncel.2018.00529.
[35] Fakhoury M. Microglia and astrocytes in Alzheimers disease: implications for therapy[J]. Curr Neuropharmacol, 2018, 16(5): 508-518.
[36] Li DM, Zhang G, Wang ZY, et al. Idebenone attenuates ferroptosis by inhibiting excessive autophagy via the ROS-AMPK-mTOR pathway to preserve cardiac function after myocardial infarction[J]. Eur J Pharmacol, 2023, 943: 175569. doi:10.1016/j.ejphar.2023.175569.
[1] ZHANG Xiufang, LI Peizheng, ZHANG Bohan, SUN Congcong, LIU Yiming. Protective effect and mechanism of growth differentiation factor-15 in LPS-induced models of Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 1-7.
[2] SONG Luoqing, ZHOU Guoyu, YE Xiang, LU Mei, ZHAO Xinjing. A case report of misdiagnosed cerebral amyloid angiopathy-related inflammation and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 119-122.
[3] LIU Liwen, MA Jun, LI Peizheng, ZHANG Xiufang, LIU Yiming. Caregiver burden and influencing factors of 128 patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 45-49.
[4] ZHAO Hailong, WANG Hao, FANG Yuqing, MAO Fei, ZHAO Zhangning, TIAN Xiangqi, XU Xinrong, WANG Min, LI Xiuhua. Efficacy of additional idebenone in the treatment of 34 patients with Parkinsons disease with depression [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 38-44.
[5] TIAN Xiangqi, WANG Hao, XU Xinrong, FANG Yuqing, MAO Fei, ZHAO Zhangning, ZHAO Hailong, WU Bingyun, LI Xiuhua. Efficacy of ultra-low frequency transcranial magnetic stimulation in patients with Parkinsons disease sleep disorders [J]. Journal of Shandong University (Health Sciences), 2022, 60(12): 19-25.
[6] YU Shujuan, WANG Meijuan, CHEN Li, CAO Yingjuan LYU Xiaoyan, LIU Xueyan, LIN Peng, YAN Jingzheng. Influencing factors of mild cognitive impairment in elderly patients with type 2 diabetes [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 108-112.
[7] LI Ning, WANG Cuilan, ZHANG Yurong. Association analysis of cerebral artery Doppler index and serum EGF level with arteriosclerosis and cognitive impairment in 60 patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 61-66.
[8] LI Xiangqing, YIN Xin, ZHAO Xuelian, ZHAO Peiqing. Expression and clinical significance of circulating CD56bright subset of NK cells in patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 34-40.
[9] KONG Wencheng, XU Guangrun, JIA Junli, CUI Xinyu. Cerebrotendinous xanthomatosis: a case report and literature review [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 72-75.
[10] WANG Yuyu, GAO Li, CHEN Shaohua. Association between cognitive impairment and thyroid function after acute ischemic stroke in 94 patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 56-61.
[11] ZHANG Xiaotao, HE Tianqi, ZHU Meijia, TANG Jiyou, ZHAO Zhangning, MAO Fei, FANG Yuqing, LIU Xiaomin, MA Gaoting, ZHANG Xiaoyu, ZHANG Xiao, WANG Min, LI Xiuhua. Clinical observation of the effects of idebenone on Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 34-41.
[12] ZHANG Xiaoqian, MENG Xiangshui, REN Qingguo, NAN Xiaomin, AN Panpan, SHUAI Xinyan, XIA Xiaona, WANG Xuan. Magnetic resonance spectroscopy in patients with vascular cognitive impairment no dementia [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 42-46.
[13] GUO Pei, LI Xiuhua, ZHANG Xiaotao, HE Tianqi, ZHU Meijia, TANG Jiyou, ZHAO Zhangning, MAO Fei. Clinical characteristics and influencing factors of sleep disorders in patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2018, 56(4): 76-80.
[14] MI Te, QU Chuanqiang, WANG Xiang, YIN Ling, XUE Yuan, DU Yifeng. Correlation between serum amyloid A and cognitive function of patients with acute cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 40-45.
[15] DONG Fang, DU Yifeng. Correlation among cognitive impairment and high homocysteinemia as well as the number and volume of infarct in patients with lacunar cerebral infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 46-49.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd