Different androgen deprivation therapies might have a differential impact on cognition - An analysis from a population-based study using time-dependent exposure model

Cancer Epidemiol. 2020 Feb:64:101657. doi: 10.1016/j.canep.2019.101657. Epub 2020 Jan 7.

Abstract

Background: Androgen deprivation therapy (ADT) remains the mainstay treatment for locally advanced or metastatic prostate cancer (PC). However, potential effects of ADT treatment on neurocognitive dysfunction remain unclear. The present study was conducted to assess the relation between ADT treatment and risk of cognitive decline in Asian men with PC.

Methods: A population-based cohort of 24,464 men with PC, each newly diagnosed between 2000 and 2008, was selected from the Taiwan National Health Insurance Database. Subjects were further grouped by treatment as non-ADT (n = 4685) or ADT (n = 12,740), members of the latter subjected to bilateral orchiectomy or medical treatment (ie, luteinizing hormone-releasing hormone agonists, antiandrogens, or combination therapy). A multivariable Cox proportional hazard model with ADT as time-dependent covariate was used to generate adjusted hazard ratios (HRs) of subsequent cognitive decline, including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD).

Results: ADT showed a significant association with overall risk of cognitive decline (HR = 1.51, 95 % CI: 1.31-1.74), especially for PD, dementia, and non-Alzheimer dementia (non-AZD). When stratified by various ADT regimens, antiandrogen-only recipients displayed significantly heightened risks of subsequent AD, non-AZD, and PD. However, combined androgen blockade also imposed an increased risk of PD. There was no apparent correlation between duration of ADT exposure and cognitive dysfunction.

Conclusions: Various ADT therapies may have disparate impacts on cognitive function. Prospective studies exploring pertinent clinical characteristics more fully are needed to confirm these findings.

Keywords: Alzheimer disease; Androgen deprivation therapy; Cognitive decline; Combined androgen blockade; Dementia; Prostate cancer; Time-dependent exposure model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Cognition / drug effects
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / etiology
  • Cohort Studies
  • Combined Modality Therapy
  • Databases, Factual
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Male
  • Middle Aged
  • Orchiectomy / adverse effects
  • Orchiectomy / statistics & numerical data
  • Proportional Hazards Models
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Taiwan / epidemiology

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone