Link Found Between Dementia Risk and ADT for Prostate Cancer

Kevin Nead, MD

New research suggests an increased risk of dementia in men with prostate cancer being treated with androgen deprivation therapy (ADT)—marking the first study to show a significant association between dementia and the testosterone-lowering therapy.

The research team at Penn Medicine found a doubling of dementia risk and that the patients with the highest risk were those treated with ADT for the longest period of time.

“Currently there is a lot of discussion about how we treat patients with prostate cancer, how we screen prostate cancer and whether we potentially give some patients more treatment then they may benefit from,” said lead author Kevin Nead, MD. “I think in that environment, the findings about side effects from that treatment are very important because they might kind of change the conversation a little bit.”

The study, published in JAMA Oncology, included 9272 individuals with prostate cancer, and of those, 1826 men received ADT. Researchers used a text-processing method to analyze electronic medical record data from Stanford University Hospital from 1994 to 2013. The median follow-up was 3.4 years.

Researchers found that the absolute increased risk of developing dementia was 4.4% at 5 years: 7.9% among those who received ADT versus 3.5% in those who did not.

Individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia. There was no evidence of an interaction between use of ADT and age. The mean age of the patients was 66.9 years.

Last year, researchers published a study that discovered an association between Alzheimer’s disease and ADT, which has been a common treatment for prostate cancer since the 1940s. However, the study reported here suggests a broader neurocognitive risk, explained Nead, a resident in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania. There are ways that ADT and low testosterone can increase the risk of something like dementia.

“Testosterone is really important for the health of neurons in the brain, and if you lower testosterone you kind of decrease the ability of the body to prevent damage or repair things when they need to be repaired,” he said.

“ADT and low testosterone also increase cardiometabolic disease risk, and that can lead to changes in cardiovascular and vascular function, which might decrease many tissues, one of them being the brain.”

Although the findings of this study are significant, Nead further evidence will be needed through research and controlled studies. He also reminded that ADT is still a proven effective treatment for prostate cancer.

“I think at this point, based on very early research that is more hypothesis-generating, we need to do more research,” said Nead. “It would be really hard to justify not using a medication that we know extends life for a possible negative consequence that at this point is potential, probable at best, but not proven.”

Nevertheless, Nead said: “This is not an academic question anymore; this is really a clinical question that needs to be answered. We have two papers here showing very similar outcomes and magnitude of risk, which I think supports the case for this to be studied prospectively.”

Nead KT, Gaskin G, Chester C, et al. Association between androgen deprivation therapy and risk of dementia [published online October 13, 2016]. JAMA Oncol.