Dataset Information

Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease.

ABSTRACT:

Background

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.

Objective

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.

Methods

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.

Results

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).

Conclusions

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.

SUBMITTER: Bhattarai K

PROVIDER: S-EPMC10531148 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease.

Bhattarai Kritib K Rajaganapathy Sivaraman S Das Trisha T Kim Yejin Y Chen Yongbin Y Dai Qiying Q Li Xiaoyang X Jiang Xiaoqian X Zong Nansu N

Journal of the American Medical Informatics Association : JAMIA 20230901 10

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>In this study, we selected ...[more]

PMID: 37463858

Similar Datasets

Project description:BackgroundAlzheimer's Disease (AD) is a progressive neurological disorder with no specific curative medications. While only a few medications are approved by FDA (i.e., donepezil, galantamine, rivastigmine, and memantine) to relieve symptoms (e.g., cognitive decline), sophisticated clinical skills are crucial to optimize the appropriate regimens given the multiple coexisting comorbidities in this patient population.ObjectiveHere, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude records from Electronic Health Records (EHR).MethodsIn this study, we withdraw 1,736 patients fulfilling our criteria, from the Alzheimer's Disease Neuroimaging Initiative(ADNI) database. We focused on the two most frequent concomitant diseases, depression, and hypertension, thus resulting in five main cohorts, 1) whole data, 2) AD-only, 3) AD-hypertension, 4) AD-depression, and 5) AD-hypertension-depression. We modeled the treatment learning into an RL problem by defining the three factors (i.e., states, action, and reward) in RL in multiple strategies, where a regression model and a decision tree are developed to generate states, six main medications extracted (i.e., no drugs, cholinesterase inhibitors, memantine, hypertension drugs, a combination of cholinesterase inhibitors and memantine, and supplements or other drugs) are for action, and Mini-Mental State Exam (MMSE) scores are for reward.ResultsGiven the proper dataset, the RL model can generate an optimal policy (regimen plan) that outperforms the clinician's treatment regimen. With the smallest data samples, the optimal-policy (i.e., policy iteration and Q-learning) gained a lesser reward than the clinician's policy (mean -2.68 and -2.76 vs . -2.66, respectively), but it gained more reward once the data size increased (mean -3.56 and -2.48 vs . -3.57, respectively).ConclusionsOur results highlight the potential of using RL to generate the optimal treatment based on the patients' longitude records. Our work can lead the path toward the development of RL-based decision support systems which could facilitate the daily practice to manage Alzheimer's disease with comorbidities.

Project description:BackgroundGenome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful.MethodsTo address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein-protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics. When applied to AD, this approach integrates GWAS findings, multi-omics data from brain samples of AD patients and AD transgenic animal models, drug-target networks, and the human protein-protein interactome, along with large-scale patient database validation and in vitro mechanistic observations in human microglia cells.ResultsThrough this approach, we identified 103 ARGs validated by various levels of pathobiological evidence in AD. Via network-based prediction and population-based validation, we then showed that three drugs (pioglitazone, febuxostat, and atenolol) are significantly associated with decreased risk of AD compared with matched control populations. Pioglitazone usage is significantly associated with decreased risk of AD (hazard ratio (HR) = 0.916, 95% confidence interval [CI] 0.861-0.974, P = 0.005) in a retrospective case-control validation. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR) agonist used to treat type 2 diabetes, and propensity score matching cohort studies confirmed its association with reduced risk of AD in comparison to glipizide (HR = 0.921, 95% CI 0.862-0.984, P = 0.0159), an insulin secretagogue that is also used to treat type 2 diabetes. In vitro experiments showed that pioglitazone downregulated glycogen synthase kinase 3 beta (GSK3β) and cyclin-dependent kinase (CDK5) in human microglia cells, supporting a possible mechanism-of-action for its beneficial effect in AD.ConclusionsIn summary, we present an integrated, network-based artificial intelligence methodology to rapidly translate GWAS findings and multi-omics data to genotype-informed therapeutic discovery in AD.

Dataset Information

Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease.

Background

Objective

Methods

Results

Conclusions

Publications

Using artificial intelligence to learn optimal regimen plan for Alzheimer's disease.

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