Study Finds Association Between Androgen-Deprivation Therapy in Prostate Cancer and Risk of Alzheimer’s Disease


Key Points

  • Use of androgen-deprivation therapy was associated with an increased risk of Alzheimer’s disease.
  • This risk increased with increasing duration of use of androgen-deprivation therapy.

In a retrospective analysis reported in the Journal of Clinical Oncology, Nead et al found that use of androgen-deprivation therapy in the treatment of prostate cancer was associated with an increased risk of subsequent Alzheimer’s disease.

Study Details

In the study, a text-processing pipeline was used to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mount Sinai, New York, hospitals, including the International Classification of Diseases–9th revision Diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. The association of androgen-deprivation therapy use with diagnosis of Alzheimer’s disease was assessed using a 1:5 propensity score–matched analysis and a multivariable Cox proportional hazards analysis.

Men who received chemotherapy were excluded from the main analyses (due to evidence of an association with cognitive dysfunction and an expected correlation with Alzheimer’s disease), as were those with a history of dementia or stroke. Analyses were adjusted for age at prostate cancer diagnosis; race; smoking status; use of antiplatelet, anticoagulant, antihypertensive, and statin medications; and history of cardiovascular disease, diabetes, or other malignancy.

Increased Risk

Of 16,888 patients with prostate cancer included in the analysis, 2,397 (14.2%) received androgen-deprivation therapy and 14,491 did not during a median follow-up of 2.7 years. Kaplan-Meier analysis showed a lower cumulative probability of remaining free of Alzheimer’s disease among androgen-deprivation therapy users in the entire cohort (P = .001) and in the propensity score–matched cohort (including 11,985 androgen-deprivation therapy nonusers; P = .021). Use of androgen-deprivation therapy was associated with an increased risk of Alzheimer’s disease in both the propensity score–matched analysis (hazard ratio [HR] = 1.88, P = .021) and multivariate Cox regression analysis (HR = 1.66, P = .031).

Risk of Alzheimer’s disease was nonsignificantly increased with androgen-deprivation therapy use < 12 months vs no use (HR = 1.62, P = .165) and significantly increased with use ≥ 12 months (HR = 2.12, P = .011), with an overall increase in risk according to increasing duration of use (P = .016 for trend). A propensity score–matched analysis, including patients who received chemotherapy, yielded similar results for androgen-deprivation therapy use vs nonuse (HR = 1.96, P = .016).

The investigators concluded: “Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer’s disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.”

The study was supported by the National Institutes of Health.

Kevin T. Nead, MD, MPhil, of the University of Pennsylvania, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.