Virginia Via Research Day Book 2026

Medical Student Research Clinical

UNDERSTANDING SOCIOECONOMIC, PSYCHOSOCIAL, AND CLINICAL DETERMINANTS OF ALZHEIMER’S DISEASE RISK AMONG APOE4-POSITIVE ADULTS AGED 65 AND OLDER

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Cameron Woo; Alycia Auerbeck; Lileen Rochelle; Christian Woo Corresponding author: aauerbeck@vcom.edu

VCOM-Virginia, Blacksburg, Virginia

Cognitive resilience—the ability to sustain cognitive functioning despite underlying neurodegenerative changes—varies widely among older adults, yet the factors driving this variation remain unclear. Understanding how demographic, psychosocial, and clinical influences interact to shape resilience is especially important in individuals at heightened biological risk. Alzheimer’s disease (AD) is particularly common among carriers of the APOE4 allele, but genetic susceptibility alone does not account for the wide differences in disease onset and severity observed in this population. Emerging evidence points to socioeconomic conditions, mental health, and clinical comorbidities as potential modifiers of cognitive vulnerability, yet their combined impact among APOE4 positive older adults has not been well defined. We seek to determine which non-genetic factors are most strongly associated with the presence of AD among APOE4-positive adults aged 65 years and older. We hypothesize that adverse socioeconomic, psychosocial, and clinical conditions will be associated with a significantly greater likelihood of AD compared to those without such exposures. Utilizing the All of Us research database, we conducted a retrospective observational cohort study. Two

cohorts were constructed utilizing the All of Us Cohort Builder: one case cohort comprised of APOE4-positive participants aged 65 years and older with AD and one control cohort comprised of APOE4-positive participants aged 65 years and older without AD. Participant data were extracted across various domains through the Dataset Builder, including demographics (age, sex, race, ethnicity, education, and income), socioeconomic measures (food insecurity, financial strain, employment, and insurance), mental health and quality-of-life variables, lifestyle behaviors (tobacco, alcohol use, and physical activity), and clinical markers (BMI, blood pressure, lipid profiles, hypertension, and diabetes). Datasets were exported as CSV files and merged, utilizing “person_id” as a unique identifier for each participant. Logistic regression models were used to assess associations between each variable and AD status, adjusting for confounders. Additionally, propensity score matching was performed as a sensitivity approach. Odds ratios, 95% confidence intervals, and p-values were calculated for all predictors. Our final analytic cohort consisted of 8,421 APOE4 positive cases and 952,186 APOE4-positive controls. In fully adjusted models, hypertension (OR ~ 4.29), low health literacy (OR ~ 2.11), poor mental health (OR ~ 1.59), and lower BMI (OR ~ 0.94) emerged as the

strongest independent predictors of AD. Socioeconomic variables and social support remained significant in crude comparisons but lost strength when controlling for these dominant clinical and psychosocial factors. These findings demonstrate that cognitive resilience among genetically high-risk older adults is shaped not only by APOE4 status but also by modifiable vascular, literacy-related, and mental health factors. By clarifying how non-genetic influences interact with APOE4 related vulnerability, this study highlights key targets for interventions aimed at strengthening cognitive resilience in aging populations. Findings from this research have the potential to clarify mechanisms underlying individual differences in cognitive decline and support the development of a more effective approach to tackling dementia care.

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187 2026 Research Recognition Day