Social determinants of health modify the association of Alzheimer's disease pathology with cognitive abilities but not of apolipoprotein E‐ ε 4 with Alzheimer's disease pathology

Abstract INTRODUCTION Apolipoprotein E (APOE) ‐ ε 4 and social determinants of health (SDoH) are major Alzheimer's disease (AD) risk factors, yet whether SDoH modify the relationship between APOE‐ ε 4, AD pathology, and cognition remains unclear. METHODS Using Biobank for Aging Studies (BAS) data, we assessed APOE‐ ε 4 using polymerase chain reaction (PCR), AD pathology using immunohistochemistry, and cognitive abilities using Clinical Dementia Rating – Sum of Boxes (CDR‐SB). RESULTS In 1,193 individuals (mean [SD] age 73.4 [13.0] years; 50.1% women; 65.4% White), APOE‐ ε 4 carriers had higher odds of AD pathology (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.85; 5.51; p < 0.001), and AD pathology was associated with poorer cognition ( β = 8.07, 95% CI: 7.47; 8.67; p < 0.001). SDoH modified this pathology–cognition association ( p = 0·002), which was stronger in the unfavorable ( β = 9.09, 95% CI: 8.00; 10.19, p < 0.001) versus the favorable SDoH profile ( β = 6.39, 95% CI: 5.42; 7.37; p < 0.001). SDoH did not modify the APOE‐ ε 4–pathology association ( p = 0.806), and no race effect modification was observed. DISCUSSION AD pathology was more strongly associated with poorer cognition in unfavorable SDoH profiles, highlighting SDoH as targets for AD prevention.