Androgen deprivation therapy and cognitive trajectories in Indian men: A 36-month prospective matched cohort analysis with Addenbrooke’s cognitive examination-III

ABSTRACT Introduction: Androgen deprivation therapy (ADT), widely used in men with advanced prostate cancer, has been implicated in cognitive decline. Evidence from Western cohorts remains inconsistent, with limited long-term and India-specific data. Methods: We conducted a prospective, observational case–control study between July 2021 and December 2024 with a minimum 36-month follow-up. Men initiating ADT (luteinizing hormone-releasing hormone analogues or bilateral orchidectomy) were compared with a control cohort (benign prostatic hyperplasia or postradical prostatectomy without ADT). Groups were matched for age, baseline Addenbrooke’s cognitive examination III (ACE-III) score, G8 frailty score, and gait speed. Cognitive assessments were performed every 6 months using the culturally validated Hindi ACE-III tool. The primary outcome was the change in total ACEII score over 36 months; secondary outcomes included domain-wise changes and correlations with frailty and gait speed. Results: Sixty men were enrolled (30 per group); 21 men received ADT, and 23 served as controls, completing follow-up. Over 36 months, both groups showed modest declines in cognition, with a mean decline of −2.30 ± 1.13 for the ADT group and −1.87 ± 1.62 for the control group (P = 0.638). Domain-wise changes (attention, memory, fluency, language, and visuospatial) were small and statistically similar. Stratified analyses by frailty (G8 ≤ 14 vs. >14) and gait speed (≤0.6 m/s vs. >0.6 m/s) revealed parallel trajectories in both groups, with no effect of ADT. Conclusions: In this 36-month prospective study using a culturally validated tool, ADT was not associated with accelerated global or domain-specific cognitive decline compared to a matched cohort without ADT. These findings suggest that in appropriately selected patients, ADT can be administered without undue concern for disproportionate cognitive deterioration.