Androgen Deprivation Therapy Associated with Dementia Risk

Androgen deprivation therapy (ADT) for the treatment of prostate cancer may be associated with an increased risk of dementia, according to a new study.

“Our previous study published in 2015, which showed an association between androgen deprivation therapy and Alzheimer’s disease, was motivated by the observation that low androgens and androgen deprivation therapy might increase Alzheimer’s disease risk through specific mechanisms, such as modulation of beta-amyloid protein levels,” said study lead author Kevin T. Nead, MD MPhil, a resident in the department of radiation oncology at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. “However, low androgens and androgen deprivation therapy have been shown to more globally impact neurovascular function and, therefore, could reasonably impact all-cause dementia risk. Our finding that androgen deprivation therapy increases all-cause dementia risk suggests that many more men could potentially be adversely impacted by this treatment.”

The researchers used a text-processing method to analyze electronic medical record data from an academic medical center cohort from 1994-2013, with a median follow-up of 3.4 years. They identified 9455 individuals with prostate cancer 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. The investigators excluded 183 patients with a previous diagnosis of dementia. The final cohort was comprised of 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT.

Among 9272 men with prostate cancer, propensity score-matched Cox proportional hazards regression analysis supported a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs. 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36). Kaplan-Meier analysis demonstrated ADT users 70 years or older had the lowest cumulative probability of remaining dementia free.

“Multiple studies now suggest that androgen deprivation therapy may be associated with cognitive changes. The current certainly supports this association,” Dr Nead said. “All men should have a detailed discussion with their doctors regarding the risks and benefits of ADT. Based on the body of literature that now exists, it would be reasonable to council patients regarding potential cognitive risks as this has been shown in multiple retrospective and prospective studies. We would, however, not recommend specific changes to clinical practice based on this study alone given that androgen deprivation therapy is a life-extending treatment in some men with prostate cancer.”

 “Ultimately, evaluation of this association in prospective studies will be needed to determine whether androgen deprivation therapy causes dementia and whether this should impact patient care. Until that time, we plan to evaluate whether this risk is specific to particular types of androgen deprivation therapy and whether other medications that modulate androgens might also impact neurocognitive function.”

—Mike Bederka

Reference:

Nead KT, Gaskin G, Chester C, et al. Association between androgen deprivation therapy and risk of dementia [published online Oct. 13, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.3662.