Social determinants of health modify the association of Alzheimer's disease pathology with cognitive abilities but not of apolipoprotein E‐ε4 with Alzheimer's disease pathology

Abstract INTRODUCTION Apolipoprotein E (APOE) ‐ε4 and social determinants of health (SDoH) are major Alzheimer's disease (AD) risk factors, yet whether SDoH modify the relationship between APOE‐ε4, AD pathology, and cognition remains unclear.

Methods

Using Biobank for Aging Studies (BAS) data, we assessed APOE‐ε4 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‐ε4 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‐ε4–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.