PD15-02 DIFFERENT ANDROGEN DEPRIVATION THERAPIES HAVE UNEQUALLY IMPACT ON COGNITIVE DYSFUNCTION – AN ANALYSIS FROM A POPULATION-BASED STUDY USING TIME-DEPENDENT EXPOSURE MODEL

Abstract

Background Dementia is one of the major causes of disability and dependency in older people worldwide, which involves several types including Alzheimer's dementia, the most common variation, followed by vascular dementia, dementia with Lewy bodies, Parkinson's disease and others. Much can be offered to improve the quality of lives of people with dementia, help reduce the burden on individuals and health care system if health care professionals recognized it. Androgen deprivation therapy (ADT) has been reported to have association with an array of adverse effects including sexual dysfunction, bone demineralization, cardiovascular disease, metabolic complications, and diminished quality of life. A growing body of evidence support a link between ADT and certain types of neurocognitive dysfunction such as Alzheimer disease. However, studies have reported discordant results on the role of ADT in the development of cognitive decline or dementia. This discordance likely reflects inter-study differences in population of patients (ie, age, metastatic status, use of chemotherapy, or definition of dementia), lack of standardized outcome criteria, and length of follow-up. Stratified data with respect to subtypes of ADT achieved through surgical or medical castration were also limited. Objectives The aim of this study was to investigate the relationship between the use of androgen deprivation therapy (ADT) and the subsequent risk of cognitive decline in Asian men with prostate cancer (PC) by employing a nationwide population-based dataset. Materials and methods A population-based cohort of 24,464 men with newly diagnosed PC between 2,000 and 2008 was selected from the Taiwan National Health Insurance (NHI) Database. After excluding patients with ADT exposure, other malignancy, and diagnosis of the outcome of interests before the index date, 17,425 PC patients were included for final analysis. Patients were classified as ADT group (n = 12,740) or non-ADT comparison group (n = 4,685). A time-dependent exposure model was used, which allowed investigators to calculate the exposure period from the different usage of various kinds of ADT. The Multivariable Cox proportional hazard model with time-dependent covariates was used to estimate adjusted hazard ratios (HRs) of cognitive decline associated with different kinds of ADT treatment. Results and conclusion Among 17,425 men with PC, there was a statistically significant association between ADT use and risk of overall cognitive decline (hazard ratio, HR, 1.51; 95% CI, 1.31-1.74). ADT users had a 1.83-fold risk of Parkinson's disease and 1.38-fold risk of dementia correspondingly (95% CI = 1.44-2.34 and 1.17-1.63, respectively). After further investigating the subtypes of dementia, non-Alzheimer's dementia (non-AZD) rather than Alzheimer's dementia (AD) demonstrated a significant higher association with ADT use. Anti-androgen alone were associated with subsequent AD, non-AZD, and Parkinson disease. However, an increased risk of Parkinson's disease was only observed in combined androgen blockade (CAB) group. The duration of ADT showed no association with cognitive dysfunction. This population-based study demonstrated that antiandrogens alone was associated with a higher risk of overall cognitive dysfunction, overall dementia, and Parkinson disease. The risk of overall cognitive decline and Parkinson's disease also appeared to be higher in CAB group. Different ADT therapies may have unequally impact on cognitive dysfunction.