Men who receive androgen deprivation therapy (ADT) for prostate cancer (PCa) are at increased risk for dementia, according to a new study.
In a retrospective cohort study of 154,089 men diagnosed with PCa from 1996 to 2003, those exposed to ADT had a significant 20% increased risk of any dementia and 14% increased risk of Alzheimer’s disease compared with men not exposed to ADT, Ravishankar Jayadevappa, PhD, of the University of Pennsylvania in Philadelphia, and colleagues reported in JAMA Network Open. Compared with men not exposed to ADT, those who received 1 to 4 doses of ADT had a 19% increased risk of both any dementia and Alzheimer’s disease. Men who received 5 to 8 doses had a 24% increased risk of any dementia and 28% increased risk of Alzheimer’s disease.
“Our results suggest that clinicians need to carefully weigh the long-term risks and benefits of exposure to ADT in patients with a prolonged life expectancy and stratify patients based on dementia risk prior to ADT initiation,” the investigators concluded.
Dr Jayadevappa’s team identified the study population using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Of the 154,089 men in the study, 62,330 received ADT within 2 years of PCa diagnosis and 91,759 did not received ADT. The ADT and no-ADT groups had mean ages of 76.0 years and 74.3 years. The study population had a mean follow-up duration of 8.3 years.
Compared with the no-ADT group, the ADT group had significantly greater proportions of men who experienced any dementia and Alzheimer’s disease (21.6% vs. 15.8% and 13.1% vs 9.4%, respectively).
“To our knowledge, this is the largest study to date examining the association between exposure to ADT and subsequent dementia in a US cohort of elderly patients with prostate cancer,” the authors stated.
With regard to study limitations, the investigators noted that they looked at data from fee-for-service Medicare enrollees aged 66 years or older who lived in a SEER region and were not enrolled in a health maintenance organization. Consequently, study findings may not be generalizable to other populations.
The study corroborates previously reported findings. For example, in a paper published in JAMA Oncology in 2017, Kevin T. Nead, MD, of Stanford University School of Medicine in Stanford, California, reported on a study of 9272 men with PCa showing that ADT recipients had a significant 2-fold increased risk of dementia compared with patients who did not receive ADT. In that study, the absolute risk of dementia at 5 years was 7.9% in the ADT group compared with 3.5% in the no-ADT group.
In addition, at the American Urological Association’s 2019 annual meeting in Chicago, Karl Heinrich Tully, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues reported on a retrospective study of 100,414 men with PCa aged 66 years or older demonstrating that patients who received pharmacologic ADT, compared with those who did not, had a significant 22% increased risk of dementia and 29% increased risk of Alzheimer’s disease.
Some studies, however, have not demonstrated a link between ADT use and dementia. For example, a study of 45,218 men with PCa followed up for a median of 6.8 years found no significant association between ADT use and any dementia, vascular dementia, and Alzheimer’s disease. The study, by Rishi Deka, PhD, of the University of California San Diego School of Medicine, included men diagnosed with nonmetastatic PCa in the Veterans Affairs San Diego Health Care System. They published their findings in JAMA Oncology.
Jayadevappa R, Chhatre S, Malkowicz B, et al. Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer. JAMA Netw Open. 2019. Published online ahead of print.
Krasnova A, Tully KH, Epstein M, et al. Risk of dementia following androgen deprivation therapy for treatment of prostate cancer. Presented at the 2019 American Urological Association annual meeting held May 3-6 in Chicago. Abstract PD30-12.
Nead KT, Gaskin G, Cheser C, et al. Association between androgen deprivation therapy and risk of dementia. JAMA Oncol. 2017;3:49-55.
Deka R, Simpson DR, Bryant AK, et al. Association of androgen deprivation therapy with dementia in men with prostate cancer who receive definitive radiation therapy. JAMA Oncol. 2018;4:1616-1617.