ADT Associated With Alzheimer Disease, Dementia in Prostate Cancer Survivors

Androgen deprivation therapy (ADT) increases the risk of subsequent Alzheimer disease and dementia among men ≥66 years with prostate cancer (PC), according to findings of a large retrospective study (N = 154,089) that examined the link between ADT treatment and later cognitive dysfunction.¹ Investigators said patients with PC who received ADT were more likely to receive a diagnosis of Alzheimer disease or dementia than those not treated with ADT.

Specifically, 13.1% of men treated with ADT were later given an Alzheimer disease diagnosis compared with 9.4% who did not receive ADT (HR, 1.14). Investigators said 21.6% of patients treated with ADT developed dementia compared with 15.8% who did not (HR, 1.20).

Additionally, patients who underwent ADT for an extended duration, defined as ≥5 doses of ADT, were more likely to develop Alzheimer disease or dementia than those who completed a shorter ADT regimen. Men who received 1 to 4 doses of ADT were 1.19 times more likely to develop Alzheimer disease or dementia than those who received no ADT; for those who received 5 to 8 doses, the hazard ratios for risk of Alzheimer disease and dementia were 1.28 and 1.24, respectively (Table).¹

The study explored ADT exposure in men who had received a PC diagnosis between 1996 and 2003. Investigators followed the cohort until 2013. Although the mean follow-up after PC diagnosis was 8.3 years, investigators noted that dementia can have a latency period of ≥1 decades prior to cognitive manifestation. Alzheimer disease is the most common form of dementia.² Conversely, dementia is not a type of disease, but a syndrome.

Investigators used data from the Surveillance, Epidemiology, and End Results Medicare database to calculate the proportion of patients treated with ADT at each hospital referral region included in the study. They classified the regions as either high- or low-treatment areas to reflect the variation of ADT use by region. Men exposed to ADT were more likely to live in nonmetropolitan areas (16.7% vs 10.4%).

Of the evaluable cohort, 62,330 men received ADT within 2 years of PC diagnosis; of those, 8137 received a diagnosis of Alzheimer disease and 13,463 were given a diagnosis of dementia. Patients treated with ADT were generally older at the time of cancer diagnosis than those who were not exposed (mean, 76.0 vs 74.3 years). ADT-treated men were also more likely to be unmarried (33.7% vs 30.4%), to have more aggressive cancer (34.3% vs 17.8%), and have at least 1 comorbidity (32.0% vs 17.4%).

Comorbidity was the focus of a sensitivity analysis of the association of ADT and diagnosis of Alzheimer disease or dementia in 3 subgroups: no comorbidities, 1 to 2 comorbidities, and >2 comorbidities. A connection between ADT treatment and diagnosis of Alzheimer disease was visible in only the group with no comorbidities (HR, 1.22).

Investigators said that based on this study, ADT can increase the risk for Alzheimer disease and dementia and that clinicians should therefore consider the potential for ADT-related cognitive dysfunction in patients who have a prolonged life expectancy. They also recommended stratifying patients based on Alzheimer and dementia risk prior to ADT initiation.

The retrospective cohort study was the largest analysis to date of the association between ADT exposure and subsequent dementia in a population of elderly US men with prostate cancer, according to investigators.

References

1. Jayadevappa R, Chhatre S, Malkowicz SB, Parikh RB, Guzzo T, Wein AJ. Association between androgen deprivation therapy use and diagnosis of dementia in men with prostate cancer. JAMA Netw Open. 2019;2(7):e196562. doi: 10.1001/jamanetworkopen.2019.6562.
2. Kandola A. What is the difference between dementia and Alzheimer’s? Medical News Today website.medicalnewstoday.com/articles/ 323283.php. Updated October 9, 2018. Accessed July 16, 2019.