Abstract

Alzheimer's disease (AD) is a progressive neurological disorder with no specific curative medications. Sophisticated clinical skills are crucial to optimize treatment regimens given the multiple coexisting comorbidities in the patient population. Here, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude data from electronic health records. In this study, we selected 1736 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We focused on the two most frequent concomitant diseases-depression, and hypertension, thus creating 5 data cohorts (ie, Whole Data, AD, AD-Hypertension, AD-Depression, and AD-Depression-Hypertension). We modeled the treatment learning into an RL problem by defining states, actions, and rewards. We built a regression model and decision tree to generate multiple states, used six combinations of medications (ie, cholinesterase inhibitors, memantine, memantine-cholinesterase inhibitors, hypertension drugs, supplements, or no drugs) as actions, and Mini-Mental State Exam (MMSE) scores as rewards. Given the proper dataset, the RL model can generate an optimal policy (regimen plan) that outperforms the clinician's treatment regimen. Optimal policies (ie, policy iteration and Q-learning) had lower rewards than the clinician's policy (mean -3.03 and -2.93 vs. -2.93, respectively) for smaller datasets but had higher rewards for larger datasets (mean -4.68 and -2.82 vs. -4.57, respectively). Our results highlight the potential of using RL to generate the optimal treatment based on the patients' longitude records. Our work can lead the path towards developing RL-based decision support systems that could help manage AD with comorbidities.

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