Association of apolipoprotein E genotype with cognitive performance: findings from the University of California, Davis Alzheimer's Disease Research Center longitudinal diversity cohort.

INTRODUCTION

The apolipoprotein E (ApoE) ε4 allele is a key genetic risk for Alzheimer's disease, but its effects may differ by heritage. We examined how ApoE4 influences hippocampal volume, episodic memory, and clinical syndrome across race and ethnicity (ethnoracial) groups.

METHODS

We analyzed 946 participants with the ApoE genotype, clinical diagnosis, and magnetic resonance imaging scans. Regression and structural equation modeling tested ApoE4's impact on cognition and whether an ethnoracial group consisting of 486 White, 234 Black/African American, or 226 Hispanic/Latino individuals moderated these effects.

RESULTS

ApoE4 prevalence increased with the clinical syndrome (odds ratio [OR] = 3.0, p < 0.0001). It correlated with lower hippocampal volume (ß = -0.14, p < 0.001) and weaker memory performance (ß = -0.21, p < 0.001). The indirect effect of ApoE4 via hippocampal volume was largest among White participants.

DISCUSSION: ApoE4's influence on hippocampal volume, episodic memory and clinical syndrome varies by ethnoracial group, with the strongest effects among White individuals. Our findings necessitate further AD biomarker research, as standard markers may not apply universally.