Early Prediction of Alzheimers Disease Leveraging Symptom Occurrences from Longitudinal Electronic Health Records of US Military Veterans

TL;DR

This study demonstrates that machine learning models analyzing longitudinal electronic health records can predict Alzheimer's disease onset up to ten years in advance with high accuracy, aiding early diagnosis and intervention.

Contribution

It introduces a novel approach using AD-related keyword occurrences in EHRs with machine learning for early AD prediction, validated across diverse subgroups.

Findings

High prediction accuracy (ROCAUC 0.997) up to ten years before diagnosis.

Model well-calibrated and consistent across most demographic groups.

Increased AD-related keywords over time as diagnosis approaches.

Abstract

Early prediction of Alzheimer's disease (AD) is crucial for timely intervention and treatment. This study aims to use machine learning approaches to analyze longitudinal electronic health records (EHRs) of patients with AD and identify signs and symptoms that can predict AD onset earlier. We used a case-control design with longitudinal EHRs from the U.S. Department of Veterans Affairs Veterans Health Administration (VHA) from 2004 to 2021. Cases were VHA patients with AD diagnosed after 1/1/2016 based on ICD-10-CM codes, matched 1:9 with controls by age, sex and clinical utilization with replacement. We used a panel of AD-related keywords and their occurrences over time in a patient's longitudinal EHRs as predictors for AD prediction with four machine learning models. We performed subgroup analyses by age, sex, and race/ethnicity, and validated the model in a hold-out and "unseen" VHA stations group. Model discrimination, calibration, and other relevant metrics were reported for predictions up to ten years before ICD-based diagnosis. The study population included 16,701 cases and 39,097 matched controls. The average number of AD-related keywords (e.g., "concentration", "speaking") per year increased rapidly for cases as diagnosis approached, from around 10 to over 40, while remaining flat at 10 for controls. The best model achieved high discriminative accuracy (ROCAUC 0.997) for predictions using data from at least ten years before ICD-based diagnoses. The model was well-calibrated (Hosmer-Lemeshow goodness-of-fit p-value = 0.99) and consistent across subgroups of age, sex and race/ethnicity, except for patients younger than 65 (ROCAUC 0.746). Machine learning models using AD-related keywords identified from EHR notes can predict future AD diagnoses, suggesting its potential use for identifying AD risk using EHR notes, offering an affordable way for early screening on large population.