Abstract 4307: Influence of age on androgen deprivation therapy-associated Alzheimer's disease
Authors: Nead Kevin Thomas , Gaskin Greg , Chester Cariad , Swisher-McClure Samuel , Dudley Joel T. , Leeper Nicholas J. , Shah Nigam H. 
Published: July 2016

Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer with approximately 500,000 males currently receiving ADT in the United States. ADT decreases androgen levels with 20-30% of patients experiencing prolonged suppression. Concerningly, low testosterone has been shown to precede Alzheimer's disease (AD) and ADT increases β-amyloid protein levels. Here, extending prior work, we examine the association of ADT with the development of AD in an age-stratified analysis among men with prostate cancer.

We analyzed electronic medical record data at Stanford University and Mt. Sinai. Individuals with prostate cancer and follow-up ≥ 180 days after diagnosis without a history of dementia, stroke or chemotherapy were eligible. Covariates, extracted from coded and textual data, were age at prostate cancer diagnosis, race, smoking status, use of anti-platelet, anti-coagulant, anti-hypertensive and statin medications, and a history of cardiovascular disease, diabetes or malignancy. We examined the association of ADT with AD stratified by age at diagnosis. Age 70 years was selected as the cut-off given existing management guidelines for cancer patients older than 70. Hazard ratios (HRs) were calculated using 1:5 propensity score matched and traditional multivariable Cox proportional hazards models to test the association of use versus non-use of ADT, and ADT duration (no-ADT, &lt;12 months, ≥ 12 months), on risk of AD. Kaplan–Meier survival functions were compared among individuals &lt; 70, non-ADT users ≥ 70, and ADT users ≥ 70 years in the propensity score matched cohort using Cox tests for equality. A 2-sided p-value &lt; 0.05 was considered significant.

Baseline patient characteristics were well balanced after propensity score matching in the full and age ≥ 70 years subgroup (p&gt;0.07). The median follow-up period was 2.7 years (interquartile range, 1.0-5.4 years). Kaplan-Meier survival functions demonstrated a lower probability of remaining AD-free for age ≥ 70 versus &lt; 70 years (p&lt;0.001) and between ADT and non-ADT users ≥ 70 years (p = 0.034). There was a statistically significant association between ADT use and AD among those ≥ 70 years using propensity score matched (HR = 1.84; 95% confidence interval [CI], 1.07-3.17; p = 0.027) and traditional multivariable Cox regression analysis (HR = 2.04; 95% CI, 1.23-3.40; p = 0.006). Among those ≥ 70 years a longer duration of ADT was associated with a greater risk of AD (HR = 1.41; 95% CI 1.01-1.96, p = 0.043).

Among men aged 70 years or older the utilization and duration of ADT is associated with an increased rate of AD. This further supports the association between ADT and cognitive dysfunction and suggests that older men may be most susceptible. Limitations of this study include inadequate power to conduct subgroup analysis in the &lt; 70 years cohort. Prospective studies are required to determine the mechanism of this association in order to develop preventative strategies.

Citation Format: Kevin Thomas Nead, Greg Gaskin, Cariad Chester, Samuel Swisher-McClure, Joel T. Dudley, Nicholas J. Leeper, Nigam H. Shah. Influence of age on androgen deprivation therapy-associated Alzheimer's disease. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4307.