Song Jihun, Park Sun Jae, Kim Yu-Jin, Park Sang Min
Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea.
Biomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea.
Front Neurol. 2025 Aug 26;16:1628876. doi: 10.3389/fneur.2025.1628876. eCollection 2025.
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.
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)].
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).
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.
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。
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)]。
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)。
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。