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

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.

SUBMITTER: Vogelgsang J

PROVIDER: S-EPMC10517223 | biostudies-literature | 2023 Jul-Sep

REPOSITORIES: biostudies-literature

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

Vogelgsang Jonathan J Dan Shu S Lally Anna P AP Chatigny Michael M Vempati Sangeetha S Abston Joshua J Durning Peter T PT Oakley Derek H DH McCoy Thomas H TH Klengel Torsten T Berretta Sabina S

Alzheimer's & dementia (Amsterdam, Netherlands) 20230701 3

<h4>Introduction</h4>Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to <i>post-mortem</i> work, as assessments of phenotypic concepts need to rely on existing records.<h4>Methods</h4>We adapted well-validated methodologies to compute National Institute of Mental Health Research Domain Criteria (RDoC) scores using natural language processing (NLP) from electronic h ...[more]

PMID: 37745891

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