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

Abstract

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.

Keywords: Alzheimer’s disease; Anticancer drug; Cancer; Dementia; Incidence; Vascular dementia.

Figure 1

Selection of study participants. Cancer patients aged 65 years and older who received anticancer drugs between January 1, 2008 and December 31, 2018 were identified from the Korean National Health Insurance Service (K-NHIS) database (N = 116,506). Exclusions included patients who died within six months of cancer diagnosis (N = 4715), those diagnosed with a brain tumor (N = 958), or with a history of dementia before receiving anticancer drugs (N = 6116). The final analytic cohort comprised 105,283 participants.

Figure 2

Diagram of study design. Cohort entry occurred at the initiation of any anticancer drug from January 1, 2008. The follow-up period continued until the incident dementia (event date), the end of the study period (December 31, 2018), or death.

Figure 3

Kaplan–Meier curves for the incidence of dementia by anticancer drugs. (A) Cumulative incidence of dementia in patients treated with antimetabolites compared to that of all other anticancer drugs. (B) Cumulative incidence of dementia in patients treated with molecular targeted therapies compared to that of all other anticancer drugs. Among molecular targeted therapies, (C) EGFR inhibitors and (D) multikinase inhibitors show lower cumulative incidence compared to all other anticancer drugs.