Identifying clinical phenotypes of frontotemporal dementia in post-9/11 era veterans using natural language processing.

Introduction: Frontotemporal dementia (FTD) encompasses a clinically and pathologically diverse group of neurodegenerative disorders, yet little work has quantified the unique phenotypic clinical presentations of FTD among post-9/11 era veterans. To identify phenotypes of FTD using natural language processing (NLP) aided medical chart reviews of post-9/11 era U.S. military Veterans diagnosed with FTD in Veterans Health Administration care. Methods: A medical record chart review of clinician/provider notes was conducted using a Natural Language Processing (NLP) tool, which extracted features related to cognitive dysfunction. NLP features were further organized into seven Research Domain Criteria Initiative (RDoC) domains, which were clustered to identify distinct phenotypes. Results: Veterans with FTD were more likely to have notes that reflected the RDoC domains, with cognitive and positive valence domains showing the greatest difference across groups. Clustering of domains identified three symptom phenotypes agnostic to time of an individual having FTD, categorized as Low (16.4%), Moderate (69.2%), and High (14.5%) distress. Comparison across distress groups showed significant differences in physical and psychological characteristics, particularly prior history of head injury, insomnia, cardiac issues, anxiety, and alcohol misuse. The clustering result within the FTD group demonstrated a phenotype variant that exhibited a combination of language and behavioral symptoms. This phenotype presented with manifestations indicative of both language-related impairments and behavioral changes, showcasing the coexistence of features from both domains within the same individual. Discussion: This study suggests FTD also presents across a continuum of severity and symptom distress, both within and across variants. The intensity of distress evident in clinical notes tends to cluster with more co-occurring conditions. This examination of phenotypic heterogeneity in clinical notes indicates that sensitivity to FTD diagnosis may be correlated to overall symptom distress, and future work incorporating NLP and phenotyping may help promote strategies for early detection of FTD.