Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology

Vogelgsang, J. S.; Dan, S.; Lally, A. P.; Chatigny, M.; Vempatia, S.; Abston, J.; Durning, P. T.; Oakley, D. H.; McCoy, T. H.; Klengel, T.; Berretta, S.

doi:10.1101/2023.05.04.539430

bioRxiv · 10.1101/2023.05.04.539430

Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology

Vogelgsang, J. S.·Dan, S.·Lally, A. P.·Chatigny, M.·Vempatia, S.·Abston, J.·Durning, P. T.·Oakley, D. H.·McCoy, T. H.·Klengel, T.·Berretta, S.

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Abstract

INTRODUCTIONTransdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to postmortem work, as assessment of newly developed phenotypic concepts needs to rely on existing records. METHODSWe adapted well-validated methodologies to compute NIMH research domain criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether RDoC cognitive domain scores were associated with hallmark Alzheimers disease (AD) neuropathological measures. RESULTSOur results confirm an association of EHR-derived cognitive scores with hallmark neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal ({beta}=0.38, p=0.0004), parietal ({beta}=0.35, p=0.0008), temporal ({beta}=0.37, p=0. 0004) and occipital ({beta}=0.37, p=0.0003) lobes. DISCUSSIONThis proof of concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from postmortem EHR.

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Vogelgsang, J. S., Dan, S., Lally, A. P., Chatigny, M., Vempatia, S., Abston, J., Durning, P. T., Oakley, D. H., McCoy, T. H., Klengel, T., Berretta, S.. 2023-05-05. Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology. https://doi.org/10.1101/2023.05.04.539430

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