Curation and validation of electronic medical record-based dementia diagnoses in the VA Million Veteran Program.

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The age distribution and diversity of the VA Million Veteran Program (MVP) cohort make it a valuable resource for studying the genetics of Alzheimer's disease (AD) and related dementias (ADRD). We present and evaluate the performance of several International Classification of Diseases (ICD) code-based classification algorithms for AD, ADRD, and dementia for use in MVP genetic studies and other studies using VA electronic medical record (EMR) data. These were benchmarked relative to existing ICD algorithms and AD-medication-identified cases. We used chart review of n = 103 MVP participants to evaluate diagnostic utility of the algorithms. Suitability for genetic studies was examined by assessing association with APOE ε4, the strongest genetic AD risk factor, in a large MVP cohort (n = 286 K). The newly developed MVP-ADRD algorithm performed well, comparable to the existing PheCode dementia algorithm (Phe-Dementia) in terms of sensitivity (0.95 and 0.95) and specificity (0.65 and 0.70). The strongest APOE ε4 associations were observed in cases identified using MVP-ADRD and Phe-Dementia augmented with medication-identified cases (MVP-ADRD or medication, p = 3.6 ×10-290; Phe-Dementia or medication, p = 1.4 ×10-290). Performance was improved when cases were restricted to those with onset age ≥60. We found that our MVP-developed ICD-based algorithms had good performance in chart review and generated strong genetic signals, especially after inclusion of medication-identified cases. Ultimately, our MVP-derived algorithms are likely to have good performance in the broader VA, and their performance may also be suitable for use in other large-scale EMR-based biobanks in the absence of definitive biomarkers such as amyloid-PET and cerebrospinal fluid biomarkers.