Abstract

Abstract Background Accurate prediction of future incidence of Alzheimer’s disease may facilitate intervention strategy to delay disease onset. Existing AD risk prediction models require collection of biospecimen (genetic, CSF, or blood samples), cognitive testing, or brain imaging. Conversely, EHR provides an opportunity to build a completely automated risk prediction model based on individuals’ history of health and healthcare. We tested machine learning models to predict future incidence of AD using administrative EHR in individuals aged 65 or older. Methods We obtained de-identified EHR from Korean elders age above 65 years old (N=40,736) collected between 2002 and 2010 in the Korean National Health Insurance Service database system. Consisting of Participant Insurance Eligibility database, Healthcare Utilization database, and Health Screening database, our EHR contain 4,894 unique clinical features including ICD-10 codes, medication codes, laboratory values, history of personal and family illness, and socio-demographics. Our event of interest was new incidence of AD defined from the EHR based on both AD codes and prescription of anti-dementia medication. Two definitions were considered: a more stringent one requiring a diagnosis and dementia medication resulting in n=614 cases (“definite AD”) and a more liberal one requiring only diagnostic codes (n=2,026; “probable AD”). We trained and validated a random forest, support vector machine, and logistic regression to predict incident AD in 1,2,3, and 4 subsequent years using the EHR available since 2002. The length of the EHR used in the models ranged from 1,571 to 2,239 days. Model training, validation, and testing was done using iterative (5 times), nested, stratified 5-fold cross validation. Results Average duration of EHR was 1,936 days in AD and 2,694 days in controls. For predicting future incidence of AD using the “definite AD” outcome, the machine learning models showed the best performance in 1 year prediction with AUC of 0.781; in 2 year, 0.739; in 3 year, 0.686; in 4 year, 0.662. Using “probable AD” outcome, the machine learning models showed the best performance in 1 year prediction with AUC of 0.730; in 2 year, 0.645; in 3 year, 0.575; in 4 year, 0.602. Important clinical features selected in logistic regression included hemoglobin level (b=-0.902), age (b=0.689), urine protein level (b=0.303), prescription of Lodopin (antipsychotic drug) (b=0.303), and prescription of Nicametate Citrate (vasodilator) (b=-0.297). Conclusion This study demonstrates that EHR can detect risk for incident AD. This approach could enable risk-specific stratification of elders for better targeted clinical trials. Key Points Question Can machine learning be used to predict future incidence of Alzheimer’s disease using electronic health records? Findings We developed and validated supervised machine learning models using the HER data from 40,736 South Korean elders (age above 65 years old). Our model showed acceptable accuracy in predicting up to four year subsequent incidence of AD. Meaning This study shows the potential utility of the administrative EHR data in predicting risk for AD using data-driven machine learning to support physicians at the point of care.