Dementia incidence varied by anticancer drugs and molecular targeted therapy in a population-based cohort study

Anticancer drugs may affect the incidence of dementia by modulating the common pathophysiology between cancer and dementia. However, there is a paucity of research that focused on anticancer drugs with different mechanisms of action and their associations with subtypes of dementia. Therefore, we aimed to investigate the incidence of dementia according to various groups of anticancer drugs. From the Korea National Health Insurance Service database, our retrospective population-based cohort study enrolled 116,506 cancer patients aged 65 years and older who received anticancer drugs between January 1, 2008 and December 31, 2018. The hazard ratio was determined using Cox proportional hazards regression models, comparing each group of anticancer drugs to all other anticancer drugs, after adjusting for covariates. Antimetabolites (HR = 0.91; 95% CI 0.84-0.97) and molecular targeted therapies (HR = 0.60; 95% CI 0.49-0.74) were associated with a decreased incidence of dementia of the Alzheimer type (DAT), but not with vascular dementia. Among molecular targeted therapies, epidermal growth factor receptor inhibitors (HR = 0.60; 95% CI 0.46-0.79) and multikinase inhibitors (HR = 0.49; 95% CI 0.27-0.89) were associated with a low incidence of DAT only. Our findings highlight the potential for targeted repurposing of anticancer drugs to prevent dementia.