ADT Linked to Increased Dementia Risk in Prostate Cancer Patients

Androgen deprivation therapy (ADT), a mainstay of treatment for men with prostate cancer, may raise the risk of dementia, according to a study published in JAMA Oncology.

“ADT has a demonstrated survival benefit in some patients with prostate cancer. However, it also has been linked to several adverse health effects,” wrote study authors led by Kevin T. Nead, MD, of Stanford University School of Medicine, Stanford, California. “A growing body of evidence supports a link between ADT and cognitive dysfunction, including Alzheimer disease.”

To examine the link between ADT and dementia, the authors analyzed medical records of prostate cancer patients treated at an academic medical center between 1994 and 2013. The final study cohort included 9,272 men with prostate cancer who had not previously been diagnosed with dementia. Among those, 1,826 patients received ADT as part of their treatment. The mean age of the men included in the study was 66.9 years. More than half of the men were white (58.8%).

After a median follow-up of 3.4 years, there were 314 cases of dementia diagnosed. The study authors found a statistically significant association between ADT use and risk of dementia (hazard ratio [HR], 2.17; P < .001). The median time to diagnosis of dementia was 4 years.

The risk of developing dementia at 5 years in men who were treated with ADT was 7.9% compared with 3.5% in those who did not receive ADT.

Men who received ADT for at least 12 months had the greatest absolute risk of dementia (HR, 2.36; P < .001). Results were similar when patients who received chemotherapy were excluded (HR, 2.35; P < .001).

“We show a dose response effect between greater duration of use of ADT and increased risk of dementia. Finally, we find that use of ADT increases the risk of dementia regardless of age, but that older men receiving ADT were the least likely to remain dementia free,” the authors wrote.

Patients treated with ADT who were 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001), according to a Kaplan-Meier analysis.

ADT use has increased dramatically in the last few decades. As many as 500,000 men currently receive ADT as a treatment for prostate cancer in the United States.

Androgens have been shown to have a role in the health and maintenance of neurons in the central nervous system and testosterone analogs have been shown to have a neuroprotective function, pointing to a potential mechanism of how ADT may have an effect on the development of dementia.

“This finding should be investigated in prospective studies given significant individual patient and health system implications if there are higher rates of dementia among the large group of patients undergoing ADT,” concluded the study authors.

Limitations of the study include the use of clinical documents and billing codes to determine a dementia diagnosis, the fact that patients who receive ADT may be poor candidates for other prostate cancer interventions due to comorbidities, and the inability to assess whether the type of ADT plays a role in dementia development.