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Impact of androgen receptor pathway inhibitors on cognitive function in older adults treated for metastatic prostate

Antoine Boué1, Giulia Baciarello2, Emmanuel Meyer3

  • 1University of Caen Normandie, Inserm 1086 Anticipe, Caen, France.

Communications Medicine
|December 23, 2025
PubMed
Abstract

Insights

Androgen receptor pathway inhibitors (ARPI) combined with androgen deprivation therapy (ADT) may negatively impact cognition in older men with metastatic prostate cancer (mPC). Healthcare providers should monitor for cognitive changes in these patients.

Area of Science:

  • Oncology
  • Neuroscience
  • Geriatrics

Background:

  • Metastatic prostate cancer (mPC) treatment often involves androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI).
  • Preliminary data suggest potential cognitive effects of ADT+ARPI, but evidence in older adults (≥70 years) is limited.
  • This study aimed to evaluate the impact of ADT+ARPI on cognitive function in elderly mPC patients.

Purpose of the Study:

  • To assess cognitive function in older adults (≥70 years) with mPC receiving ADT+ARPI.
  • To compare cognitive outcomes between patients receiving ADT+ARPI, ADT alone, and healthy controls.
  • To identify specific cognitive domains affected by ADT+ARPI treatment.

Main Methods:

  • An observational study (COG-PRO trial) involving mPC patients (≥70 years) on ADT+ARPI, ADT alone, and healthy controls.
  • Cognitive assessment included self-reported questionnaires (subjective cognition) and objective tests across six domains.
  • Analysis focused on baseline impairment rates and cognitive decline over 12 months, using adjusted scores via linear models.

Main Results:

  • At baseline, 51% of ADT+ARPI patients exhibited objective cognitive impairment, compared to 26% of ADT patients and 10% of controls.
  • After 3 and 6 months, ADT+ARPI patients reported poorer subjective cognition than ADT patients (p≤0.033).
  • Objective performance in processing speed/attention was lower in ADT+ARPI patients across all follow-up visits (p≤0.010).

Conclusions:

  • ADT+ARPI treatment may increase the risk of objective and subjective cognitive impairment in older adults with mPC compared to ADT alone.
  • The findings highlight the need for careful cognitive monitoring in this patient population.
  • Clinicians should utilize specific objective and subjective cognitive measures to detect ARPI-induced cognitive changes.

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