Abstract

The association between androgen deprivation therapy (ADT) exposure and dementia is uncertain. To analyze the association between ADT exposure and diagnosis of Alzheimer disease or dementia among elderly men with prostate cancer. 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. Androgen deprivation therapy. 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. 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. 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.

Highlights

  • Prostate cancer is the most common nonskin cancer among men in the United States.[1]

  • For 1 to 4 doses of androgen deprivation therapy (ADT), the HR was 1.19 for Alzheimer disease and 1.19 for dementia

  • For 5 to 8 doses of ADT, the HR was 1.28 for Alzheimer disease and 1.24 for dementia

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Summary

Introduction

Prostate cancer is the most common nonskin cancer among men in the United States.[1]. Decreasing androgen levels may increase risk factors for Alzheimer disease and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression.[11] There may be a causative relationship between lower testosterone levels and impaired cognitive function, perhaps via impaired neuron growth and axonal regeneration or accumulation of abnormally folded β-amyloid protein.[10,12,13,14,19] Studies using national samples have reported conflicting results regarding the diagnosis of Alzheimer disease or dementia among older patients with prostate cancer exposed to ADT.[17,18,20,21,22,23] Limitations of these studies include inadequate adjustment for cancer stage, ADT dose, and duration; reliance on single-institution data; lack of generalizability to the US population; and measured and unmeasured bias associated with cohort studies. The objective of this study was to investigate the association between exposure to ADT and subsequent diagnosis of Alzheimer disease or dementia among elderly men with prostate cancer. After adjusting for relevant covariates, ADT exposure is associated with an increased hazard of subsequent dementia

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