Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

Abstract

BackgroundPrevious studies have found an association between androgen deprivation therapy (ADT) and an increased risk of dementia and depression in elderly men. This association remains controversial, and little is known about the effects of ADT in younger men. ObjectiveTo examine the association between the receipt of ADT and these outcomes in young men aged 40–64 yr presenting with nonmetastatic prostate cancer (PCa). Design, setting, and participantsFor this observational study, we identified 9117 men aged 40–64 yr diagnosed with localized PCa between 2007 and 2014, without a pre-existing neurocognitive diagnosis, using the TRICARE military database. Outcome measurements and statistical analysisKaplan-Meier curves were fitted to compare ADT versus no ADT. We also performed a subgroup analysis in patients undergoing ADT for ≥12 mo. The association between ADT and new-onset dementia or depression was evaluated using inverse-probability-of treatment-weight–adjusted Cox proportional hazards regression analysis. Results and limitationsPatients receiving ADT had a significantly higher incidence of depression (30.2 vs 15.8 per 1000 person years) and dementia (17.9 vs 7.5 per 1000 person years). The risk of developing either outcome was higher in the ADT cohort (depression: hazard ratio [HR] 2.07, p < 0.001; dementia: HR 1.70, p = 0.052). Additionally, there was a dose-response relationship between the duration of ADT and either outcome. ConclusionsIn our cohort of young men with PCa, the receipt of ADT was associated with an increased risk of developing dementia and depression. Long-term use of ADT was associated with the highest risk of neurocognitive outcomes. Patient summaryIn this study, we looked at the risk of dementia and depression in patients <65 yr of age undergoing androgen deprivation therapy (ADT) for prostate cancer. We found that these patients had a higher risk of dementia and depression than those who did not undergo ADT.