ADT has been a cornerstone of treatment for prostate cancer since the 1940s, more than 500,000 men in the United States are currently under treatment, but data over the past year have pointed to a significant association between Alzheimer's disease and ADT. This latest study suggests that there may be even broader neurocognitive risks associated with this therapy.

Interestingly, the drastic reduction of androgen activity has been linked to several adverse side effects, and researchers have found associations between low testosterone levels and obesity, diabetes, high blood pressure, and heart disease, known risk factors for dementia. ADT and low testosterone levels have also been linked to congitive deficits. Finally, research has recently shown that men with Alzheimer's disease tended to have lower testosterone levels compared with age-matched men without Alzheimer's.

Researchers analyzed the medical records of almost 9,500 prostate cancer patients who received ADT and compared them with data from subjects who did not. Using a new, sophisticated text-processing method, they identified 9,277 men with prostate cancer (mean age: 66.9 years), which included 1,826 men who had received ADT.

Subjects in the ADT group had significantly more cases of dementia (median follow-up: 3.4 years) compared with controls, with an absolute increased risk of 4.4% at 5 years: 7.9% in those treated with ADT compared with 3.5% in controls, more than double the risk.

Their analyses suggested that there was a dose-response effect, with patients receiving ADT for at least 12 months having the greatest dementia risk. They found no association between ADT and age. In men over 70 years old treated with ADT, the probability of developing dementia after 5 years was 13.7%, compared with 6.6% in men of the same age who did not receive ADT. In men less than 70 years old treated and not treated with ADT, this risk was 2.3% vs 1%, respectively.

“This is not an academic question anymore; this is really a clinical question that needs to be answered,” said lead author Kevin T. Nead, MD, MPhil, resident, department of  radiation oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, and a fellow, Penn’s Leonard Davis Institute of Health Economics.

“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,” he added.

“As the population of older, long-term cancer survivors continues to rise, the health issues that cancer therapies can leave in their wake will become increasingly important,” said Dr. Nead. “Further studies are needed to investigate the association between this therapy and dementias, given the significant patient and health system impacts if there are higher rates among the large group of patients undergoing ADT today.”