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本文引用的文献

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Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.酪氨酸激酶抑制剂在癌症治疗中的不良反应:病理生理学、机制和临床管理。
Signal Transduct Target Ther. 2023 Jul 7;8(1):262. doi: 10.1038/s41392-023-01469-6.
2
Plasma and cerebrospinal fluid pharmacokinetics of vodobatinib, a neuroprotective c-Abl tyrosine kinase inhibitor for the treatment of Parkinson's disease.伏多巴替尼的血浆和脑脊液药代动力学,一种用于治疗帕金森病的神经保护性c-Abl酪氨酸激酶抑制剂。
Parkinsonism Relat Disord. 2023 Mar;108:105281. doi: 10.1016/j.parkreldis.2023.105281. Epub 2023 Jan 14.
3
A nationwide cohort study on diabetes severity and risk of Parkinson disease.一项关于糖尿病严重程度与帕金森病风险的全国性队列研究。
NPJ Parkinsons Dis. 2023 Jan 27;9(1):11. doi: 10.1038/s41531-023-00462-8.
4
Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia.聚焦降低脑β-淀粉样蛋白以预防和治疗痴呆症的高级药物试验综述
J Exp Pharmacol. 2022 Oct 30;14:331-352. doi: 10.2147/JEP.S265626. eCollection 2022.
5
Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.基于表型的计算网络医学发现结合保险记录数据挖掘,鉴定西地那非是治疗阿尔茨海默病的候选药物。
Nat Aging. 2021 Dec;1(12):1175-1188. doi: 10.1038/s43587-021-00138-z. Epub 2021 Dec 6.
6
Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update.帕金森病临床试验药物治疗:2022 年更新。
J Parkinsons Dis. 2022;12(4):1073-1082. doi: 10.3233/JPD-229002.
7
The Relationship between Parkinson's Disease and Acute Myocardial Infarction in Korea : A Nationwide Longitudinal Cohort Study.韩国帕金森病与急性心肌梗死之间的关系:一项全国性纵向队列研究
J Korean Neurosurg Soc. 2022 Jul;65(4):507-513. doi: 10.3340/jkns.2021.0195. Epub 2022 Mar 2.
8
Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia.酪氨酸激酶抑制剂治疗慢性髓性白血病的依从性对生存的影响。
Korean J Intern Med. 2021 Nov;36(6):1450-1458. doi: 10.3904/kjim.2021.158. Epub 2021 Nov 1.
9
Clinical Efficacy of Ruxolitinib in Patients with Myelofibrosis: A Nationwide Population-Based Study in Korea.芦可替尼治疗骨髓纤维化患者的临床疗效:韩国一项基于全国人群的研究
J Clin Med. 2021 Oct 18;10(20):4774. doi: 10.3390/jcm10204774.
10
Tyrosine Kinase Inhibitors and Vascular Adverse Events in Patients with Chronic Myeloid Leukemia: A Population-Based, Propensity Score-Matched Cohort Study.酪氨酸激酶抑制剂与慢性髓性白血病患者血管不良事件:基于人群、倾向评分匹配队列研究。
Oncologist. 2021 Nov;26(11):974-982. doi: 10.1002/onco.13944. Epub 2021 Sep 12.

尼洛替尼和伊马替尼:通过国家医保数据看治疗痴呆症和帕金森病的潜在候选药物

Nilotinib and imatinib: potential candidates for treatment of dementia and Parkinson's disease through national health insurance data.

作者信息

Song Jihun, Park Sun Jae, Kim Yu-Jin, Park Sang Min

机构信息

Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea.

Biomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea.

出版信息

Front Neurol. 2025 Aug 26;16:1628876. doi: 10.3389/fneur.2025.1628876. eCollection 2025.

DOI:10.3389/fneur.2025.1628876
PMID:40937178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12420838/
Abstract

BACKGROUND

Real-world evidence on the potential of tyrosine kinase inhibitors (TKIs) for dementia and Parkinson's Disease (PD) is crucial. This observational study aimed to evaluate TKIs, particularly nilotinib and imatinib, as potential therapeutic agents for these conditions.

METHODS

In this retrospective cohort study, 5,579 cancer patients who were prescribed TKIs (users; ≥ 40 years) within 5 years were used, while propensity score-matched patients without any record of TKIs (never users) served as the reference. An association of TKIs with dementia and PD was assessed by the Fine-Gray Model with adjusted-competitive hazard ratios (aCHRs) and 95% confidence intervals (CIs): [aCHRs (95% CIs; -value)].

RESULTS

The risk of dementia decreased when all types of TKIs [0.65 (0.48-0.88; <0.01)], imatinib [0.66 (0.48-0.89; <0.01)], and nilotinib [0.46 (0.23-0.93; <0.05)] was used in cancer patients. Additionally, the reduced risk of PD was identified in users of all [0.56 (0.33-0.97; <0.05)] and imatinib [0.55 (0.32-0.96; <0.05)]. When the risk was evaluated according to the number of times for total usage, the aCHRs for PD in the low, middle, and high-frequency groups were 0.46 (0.20-1.02), 0.78 (0.40-1.54), and 0.40 (0.15-1.05), respectively. The risk of dementia was 0.68 (0.46-0.99), 0.57 (0.36-0.90), and 0.71 (0.44-1.17) in order of frequency (from low to high).

CONCLUSION

As an observational study indicated a decreased risk of dementia and PD with long-term TKI use, imatinib and nilotinib may serve as potential therapeutic agents for these conditions, with more evidence from rigorous clinical trials to validate.

摘要

背景

酪氨酸激酶抑制剂(TKIs)治疗痴呆和帕金森病(PD)的真实世界证据至关重要。本观察性研究旨在评估TKIs,特别是尼洛替尼和伊马替尼,作为这些疾病的潜在治疗药物。

方法

在这项回顾性队列研究中,使用了5579例在5年内接受TKIs治疗的癌症患者(使用者;年龄≥40岁),同时将倾向评分匹配的无TKIs治疗记录的患者(从未使用者)作为对照。采用Fine-Gray模型评估TKIs与痴呆和PD的关联,并计算调整后的竞争风险比(aCHRs)和95%置信区间(CIs):[aCHRs(95% CIs;P值)]。

结果

癌症患者使用所有类型的TKIs[0.65(0.48-0.88;<0.01)]、伊马替尼[0.66(0.48-0.89;<0.01)]和尼洛替尼[0.46(0.23-0.93;<0.05)]时,痴呆风险降低。此外,所有使用者[0.56(0.33-0.97;<0.05)]和伊马替尼使用者[0.55(0.32-0.96;<0.05)]的PD风险降低。根据总使用次数评估风险时,低、中、高频组PD的aCHRs分别为0.46(0.20-1.02)、0.78(0.40-1.54)和0.40(0.15-1.05)。痴呆风险按频率(从低到高)依次为0.68(0.46-0.99)、0.57(0.36-0.90)和0.71(0.44-1.17)。

结论

一项观察性研究表明,长期使用TKIs可降低痴呆和PD的风险,伊马替尼和尼洛替尼可能作为这些疾病的潜在治疗药物,但需要更多严格的临床试验证据来验证。