Patients Who Receive Androgen Deprivation Therapy Risk Adverse Cognitive Changes

Abstract

TO THE EDITOR: Gonzalez et al 1 in 2015 highlighted a predilection for adverse cognitive effects by a proportion of patients who received androgen-deprivation therapy (ADT). They compared 58 patients with nonlocalized or asymptomatic metastatic prostate cancer (PCa) who were about to commence ADT and observed the participants for 12 months; the findings were compared with those from a cohort of 84 men treated with prostatectomy alone and an additional 88 men who did not have a diagnosis of PCa. They found that participants in the ADT group were more likely to demonstrate impaired cognitive performance than contemporaries in the control/ reference groups over time. Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flush interference did not moderate the impact of ADT on impaired cognitive performance. In exploratory genetic analyses, GNB3 single nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group.Whether or not ADT induces adverse cognitive changes in a proportion of patients has been disputed for many years on the basis of findings from longitudinal studies, including a number that received industry funding. To resolve the question, we undertook a randomized, controlled trial of 82 men with nonlocalized PCa who were allocated to leuprorelin (Lucrin), goserelin (Zoladex), cyproterone acetate (Androcur), or no treatment and who were reassessed at 6 and 12 months after baseline; 65 participants completed 6 months, and 62 of these continued for all 12 months of follow-up.2,3 In addition to a nontreatment PCa control group, a noncancer community reference group was evaluated.Compared with baseline assessments, men who received ADT performed worse on two of 12 tests of attention and memory; 24 of 50 patients who were randomly assigned to active treatment and who were assessed 6 months later had a clinically significant decline in one or more cognitive tests, but not one patient randomly assigned to close monitoring or from the community reference group showed a decline in any test performance. At 12 months, these findings were maintained; approximately 50% of men in all treatment groups, but none of the men in the control group, had persistent significant cognitive deterioration. Although the cognitive defects were of a magnitude comparable with sleep deprivation or mild inebriation, there was no consistent association between subjective cognitive changes and objective deficits.Our study 2,3 and the study in 2015 by Gonzalez et al 1 differ in a number of ways; first, one was a randomized, controlled trial, and the other was not. Also, although both used comprehensive selections of validated instruments, the selections differed, and Gonzalez et al 1 failed to include a specific assessment for anxiety. Both trials took into account comorbidities that, along with age, can influence cognitive performance, but it is unclear if Gonzalez et al 1 made allowances for the possible influence of non-ADT medications, especially anticholine...

Association of Androgen Deprivation Therapy With Alzheimer’s Disease: Unmeasured Confounders

“…Third, two recent studies found that patients with prostate cancer who receive ADT have higher rates of impaired cognitive performance at baseline, 7,8 which may contribute to the eventual development of AD. Of note, these studies included patients with both nonmetastatic and asymptomatic metastatic disease.…”