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

Abstract

Background: Real-world evidence on the potential of tyrosine kinase inhibitors (TKIs) for dementia and Parkinson&apos;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; p-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.