Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan

This cohort study examines the association between all-cause dementia, including Alzheimer disease, and different types of androgen deprivation therapy among patients with prostate cancer in Taiwan. Importance It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. Objective To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. Design, Setting, and Participants This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. Exposures Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. Main Outcomes and Measures The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. Results In the cohort of 23651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. Conclusions and Relevance In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings. Question Does the risk of dementia vary by type of androgen deprivation therapy among patients with prostate cancer? Findings In this cohort study of 23651 patients with newly diagnosed prostate cancer between 2008 and 2015, there was no association of the use of gonadotropin-releasing hormone agonists or orchiectomy with increased dementia risk, while antiandrogen monotherapy use was associated with a 34% increased dementia risk compared with patients who did not receive androgen deprivation therapy. Meaning These findings suggest that the use of antiandrogen monotherapy, but not gonadotropin-releasing hormone agonist or orchiectomy, requires more attention with respect to subsequent risk of dementia.