Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison

Abstract

Purpose: Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance.

Patients and methods: Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations.

Results: ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001).

Conclusion: Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

Observed rates of cognitive impairment in group of patients with prostate cancer receiving androgen-deprivation therapy (ADT+) and control group. Criteria for impaired cognitive performance: (A) scoring ≥ 1.5 standard deviations (SDs) below published norms on ≥ two tests or 2.0 SDs below published norms on ≥ one test (group differences in change over time P = .05); (B) scoring ≥ 2.0 SDs below published norms on ≥ one test (group differences in change over time P = .01).

Fig 2.

No. of tests on which participants demonstrated performance ≥ 2.0 standard deviations below published norms at each assessment. ADT+, patients with prostate cancer receiving androgen-deprivation therapy.

Fig 3.

Observed rates of scoring ≥ 2.0 standard deviations below norms on ≥ one test in group of patients with prostate cancer receiving androgen-deprivation therapy (ADT+) and control group by rs1047776 genotype.

Fig A1.

Participant flow for patients with prostate cancer receiving androgen-deprivation therapy (ADT+).

Fig A2.

Participant flow for patients with prostate cancer not receiving androgen-deprivation therapy (ADT−).

Fig A3.

Participant flow for men without prostate cancer (CA−).