Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer

Abstract

Importance: The association between androgen deprivation therapy (ADT) exposure and dementia is uncertain.

Objective: To analyze the association between ADT exposure and diagnosis of Alzheimer disease or dementia among elderly men with prostate cancer.

Design, setting, and participants: This retrospective cohort study used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare linked database. Participants were 154 089 elderly men newly diagnosed with prostate cancer between 1996 and 2003. The analyses were conducted between November 1, 2018, and December 31, 2018.

Exposure: Androgen deprivation therapy.

Main outcomes and measures: Patients receiving ADT within 2 years of prostate cancer diagnosis were identified. Survival analysis was used to determine the association between ADT exposure and diagnosis of Alzheimer disease or dementia in the follow-up period. Propensity score and instrumental variable approaches were used to minimize measured and unmeasured selection bias. The association by dose of ADT was also examined.

Results: Of the 295 733 men diagnosed with prostate cancer between 1996 and 2003, 154 089 met the study criteria. Of these, 62 330 (mean [SD] age, 76.0 [6.0] years) received ADT within 2 years of prostate cancer diagnosis, and 91 759 (mean [SD] age, 74.3 [6.0] years) did not receive ADT. Mean (SD) follow-up was 8.3 (4.7) years. Exposure to ADT, compared with no ADT exposure, was associated with a diagnosis of Alzheimer disease (13.1% vs 9.4%; difference, 3.7%; 95% CI, 3.3%-3.9%; P < .001; hazard ratio [HR], 1.14; 95% CI, 1.10-1.18) and dementia (21.6% vs 15.8%; difference, 5.8%; 95% CI, 5.4%-6.2%; P < .001; HR, 1.20; 95% CI, 1.17-1.24). For 1 to 4 doses of ADT, the HR was 1.19 (95% CI, 1.15-1.24) for Alzheimer disease and 1.19 (95% CI, 1.15-1.23) for dementia. For 5 to 8 doses of ADT, the HR was 1.28 (95% CI, 1.22-1.35) for Alzheimer disease and 1.24 (95% CI, 1.19-1.29) for dementia. For more than 8 doses of ADT, the HR was 1.24 (95% CI, 1.16-1.34) for Alzheimer disease and 1.21 (95% CI, 1.15-1.28) for dementia. The number needed to harm was 18 patients (95% CI, 17-19 patients) and 10 patients (95% CI, 9.5-11 patients) for Alzheimer disease and dementia, respectively.

Conclusions and relevance: Among elderly patients with prostate cancer, ADT exposure was associated with subsequent diagnosis of Alzheimer disease or dementia over a follow-up period of at least 10 years.

Figure 1.. Process of Cohort Selection

ADT indicates androgen deprivation therapy.

Figure 2.. Survival Curve for Alzheimer Disease

Patients exposed to androgen deprivation therapy (ADT) had a higher hazard of diagnosis of Alzheimer disease compared with those not exposed to ADT.

Figure 3.. Survival Curve for Dementia

A significantly higher hazard of diagnosis of dementia was observed for patients treated with androgen deprivation therapy (ADT) vs those not treated with ADT.