Dimensional clinical phenotyping using brain donor medical records: RDoC profiling is associated with Alzheimer's disease neuropathology.

INTRODUCTION

Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to work, as assessments of phenotypic concepts need to rely on existing records.

METHODS

We adapted well-validated methodologies to compute National Institute of Mental Health Research Domain Criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from brain donors and tested whether cognitive domain scores were associated with Alzheimer's disease neuropathological measures.

RESULTS

Our results confirm an association of EHR-derived cognitive scores with neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal (ß = 0.38,  = 0.0004), parietal (ß = 0.35, P = 0.0008), temporal (ß = 0.37, P = 0.0004) and occipital (ß = 0.37, P = 0.0003) lobes.

DISCUSSION

This proof-of-concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from EHR. The associations may accelerate brain research beyond classical case-control designs.