ALPACA: A Reinforcement Learning Environment for Medication Repurposing and Treatment Optimization in Alzheimer's Disease
Organizations: University of Colorado Boulder, United States
Abstract
Evaluating personalized, sequential treatment strategies for Alzheimer's disease (AD) using clinical trials is often impractical due to long disease horizons and substantial inter-patient heterogeneity. To address these constraints, we present the Alzheimer's Learning Platform for Adaptive Care Agents (ALPACA), an open-source, Gym-compatible reinforcement learning (RL) environment for systematically exploring personalized treatment strategies using existing therapies. ALPACA is powered by the Continuous Action-conditioned State Transitions (CAST) model trained on longitudinal trajectories from the Alzheimer's Disease Neuroimaging Initiative (ADNI), enabling medication-conditioned simulation of disease progression under alternative treatment decisions. We show that CAST autoregressively generates realistic medication-conditioned trajectories and that RL policies trained in ALPACA outperform no-treatment and behavior-cloned clinician baselines on memory-related outcomes. Interpretability analyses further indicated that the learned policies relied on clinically meaningful patient features when selecting actions. Overall, ALPACA provides a reusable in silico testbed for studying individualized sequential treatment decision-making for AD.
Figures & tables
| Characteristic | Full Dataset |
|---|---|
| Overview | |
| Visits | 12,984 |
| Unique subjects | 1,905 |
| Demographics | |
| Age (mean SD) | 76.2 7.4 |
| Range (yrs) | 55.0–103.1 |
| Policy | Cumulative Reward | Per-step Reward | Final ADNI-Mem |
|---|---|---|---|
| No Medication (baseline) | |||
| Clinician | |||
| Heuristic | |||
| A2C | |||
| PPO | |||
| SAC |
Appendix figures & tables3 assets
Supplementary material from the paper’s appendix.
Appendix
| Drug | Mapped Class |
|---|---|
| Aricept, Donepezil, Namenda, Exelon | AD Treatment |
| Lipitor, Simvastatin, Crestor, Zocor, Atorvastatin | Statin |
| Lisinopril, Atenolol, Amlodipine, Metoprolol, Norvasc, Losartan | Antihypertensive |
| Levothyroxine, Synthroid | Thyroid Hormone |
| Aspirin, Ibuprofen, Aleve, ASA | NSAID |
| Tylenol, Acetaminophen | Analgesic |
Alzheimer's Disease
Alzheimer’s disease research studies its biology, detection, progression, and care using clinical, molecular, and brain-imaging evidence.
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