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

Alzheimers Dement (Amst). 2023 Sep 22;15(3):e12464. doi: 10.1002/dad2.12464. eCollection 2023 Jul-Sep.

Abstract

Introduction: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to post-mortem 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 post-mortem 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, P = 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 post-mortem EHR. The associations may accelerate post-mortem brain research beyond classical case-control designs.

Keywords: biological specimen banks; dementia; medical informatics; natural language processing; neuropathology.