Curation of Mini Mental State Examination (MMSE) Scores in the VA Million Veteran Program (MVP): Applications for Cognitive Aging Research
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Background
Electronic health record (EHR)-linked biorepositories provide opportunities to advance epidemiological research in Alzheimer’s disease (AD) and related dementias.
Objective
Evaluate the extraction, curation, and associative validity of Mini Mental State Examination (MMSE) scores from the VA EHR for participants in the VA Million Veteran Program (MVP).
Methods
The sample (N = 49,555; 7.4% women) included a multiethnic cohort (European [68.3%], African [20.4%], Hispanic [9.0%]) with EHR-extracted MMSE scores; 30.7% were apolipoprotein E ( APOE ) ε4 carriers, and 25.8% had multiple scores. Linear regressions examined cross-sectional associations between ε4 dosage (0, 1, 2) and first and lowest MMSE scores. MMSE scores were also evaluated against MVP dementia diagnostic algorithms in participants aged ≥65 years.
Results
Among participants of European ancestry, there was a significant ε4 dose-response relationship ( p s < .001) with MMSE scores. Homozygote carriers scored lower than heterozygote carriers (M diff : first = -0.5; lowest = -0.9), who scored lower than non-carriers (M diff : first = -0.4; lowest = -0.6). Among Veterans of African and Hispanic ancestry, no dose-response relationship was observed, although ε4 carriers had lower scores than non-carriers ( p s ≤ .04). MMSE scores corresponded strongly with dementia case/control status across phenotypes: mild impairment on the MMSE was strongly associated with AD (odds ratio [OR] = 11.48), with more severe MMSE impairment showing stronger associations (moderate OR = 17.95; severe OR = 27.83).
Conclusion
This study demonstrated MMSE scores can be systematically extracted and curated from the VA EHR. Findings offer a scalable framework for future studies on risk stratification, highlighting the potential for harnessing MVP to explore genetic and clinical factors contributing to cognitive and dementia outcomes in diverse samples.
