APOE4 is associated with lower adiposity independent of total energy intake in cognitively normal older adults

Background Apolipoprotein E ε4 ( APOE4) carriers with cognitive impairment exhibit lower BMI than non-carriers, but whether APOE4 influences body composition in cognitively normal older adults remains unknown. Objective To examine the association between APOE4 carrier status and body composition in cognitively normal older adults. Methods Cross-sectional analysis of 203 cognitively normal older adults (mean age 71.4 ± 4.8 years). Body composition was assessed via dual-energy x-ray absorptiometry. Linear regression models adjusted for age, sex, total energy intake, and physical activity examined associations between APOE4 status and BMI, body fat percentage, fat mass index (FMI), and lean mass index (LMI). Results APOE4 carriers (32%, n = 65) had lower BMI (β = −1.42 kg/m 2 , p = 0.043), body fat percentage (β = −3.56%, p < 0.001), and FMI (β = −1.51 kg/m 2 , p = 0.002) compared to non-carriers (68%, n = 138). LMI did not differ between groups (β = 0.18 kg/m 2 , p = 0.43). Conclusions APOE4 carriers exhibited lower adiposity but not lean mass compared to non-carriers, independent of total energy intake and physical activity. These findings suggest APOE4 influences fat mass through metabolic mechanisms that emerge before cognitive decline. Longitudinal studies are needed to determine whether these differences contribute to AD pathogenesis.