High-Throughput Phenotyping of the Symptoms of Alzheimer Disease and Related Dementias Using Large Language Models: Cross-Sectional Study.

Abstract

Background: Alzheimer disease and related dementias (ADRD) are complex disorders with overlapping symptoms and pathologies. Comprehensive records of symptoms in electronic health records (EHRs) are critical for not only reaching an accurate diagnosis but also supporting ongoing research studies and clinical trials. However, these symptoms are frequently obscured within unstructured clinical notes in EHRs, making manual extraction both time-consuming and labor-intensive.

Objective: We aimed to automate symptom extraction from the clinical notes of patients with ADRD using fine-tuned large language models (LLMs), compare its performance to regular expression-based symptom recognition, and validate the results using brain magnetic resonance imaging (MRI) data.

Methods: We fine-tuned LLMs to extract ADRD symptoms across the following 7 domains: memory, executive function, motor, language, visuospatial, neuropsychiatric, and sleep. We assessed the algorithm's performance by calculating the area under the receiver operating characteristic curve (AUROC) for each domain. The extracted symptoms were then validated in two analyses: (1) predicting ADRD diagnosis using the counts of extracted symptoms and (2) examining the association between ADRD symptoms and MRI-derived brain volumes.

Results: Symptom extraction across the 7 domains achieved high accuracy with AUROCs ranging from 0.97 to 0.99. Using the counts of extracted symptoms to predict ADRD diagnosis yielded an AUROC of 0.83 (95% CI 0.77-0.89). Symptom associations with brain volumes revealed that a smaller hippocampal volume was linked to memory impairments (odds ratio 0.62, 95% CI 0.46-0.84; P=.006), and reduced pallidum size was associated with motor impairments (odds ratio 0.73, 95% CI 0.58-0.90; P=.04).

Conclusions: These results highlight the accuracy and reliability of our high-throughput ADRD phenotyping algorithm. By enabling automated symptom extraction, our approach has the potential to assist with differential diagnosis, as well as facilitate clinical trials and research studies of dementia.