Abstract
This study examined the relationships between mid-arm circumference (MAC) and calf circumference (CC) with cognitive performance, considering the moderating effect of apolipoprotein E ε4 allele (APOE4) status. Data from 196 older adults (65-90 years) in the General Lifestyle and AD (GLAD) study were analyzed. Cognitive performance was assessed using the CERAD neuropsychological battery, with episodic memory score (EMS) and non-memory score (NMS) as primary outcomes. Multiple linear regression analyses examined associations between MAC, CC, and waist circumference (WC) with cognition, adjusting for key covariates. Interaction effects with APOE4 status were also explored. Higher MAC (or MAC/WC) significantly correlated with better EMS, while higher CC (or CC/WC) correlated with better NMS, even after Bonferroni correction (P(B) < 0.0125). These associations were stronger in APOE4-negative individuals but not significant in APOE4-positive participants. WC was not associated with cognitive measures. The results suggest that Upper- and lower-limb musculature may play distinct roles in cognitive function, with MAC linked to episodic memory and CC to non-memory cognition, particularly in APOE4-negative individuals. These findings highlight the potential of muscle health maintenance as a strategy for preserving cognitive function in aging populations.