Allostatic Load Indices and Cognition Among Older Adults: The Moderating Role of Apolipoprotein ε4 Genotype on Metabolic Burden
Abstract
Objective: Allostatic Load (AL), an index of multisystem biological dysregulation, is linked with adverse cognitive outcomes. The Apolipoprotein E-ε4 (APOE-ε4) genetic variant is associated with an accelerated cognitive decline and Alzheimer’s disease. This study investigates the association between AL indices (nutritional deficit, adiposity, renal, glycemic, and metabolic burden) and cognition among older adults, and whether this association differs between APOE-ε4 carriers (homozygous+heterozygous) and non-APOE-ε4-carriers. Method/Data Selection: Participants with complete AL, APOE-ε4 genotype, and cognitive data from the University of Alabama at Birmingham Alzheimer's Disease Research Center Cohort were included (N = 248; Mage (years) = 69.03; 46.00% APOE-ε4 carriers). A cognitive composite z-score was derived from 12 neuropsychological tests (National Alzheimer’s Coordinating Center Unified Data Set). We used Ordinary Least Squares regression with age, education, sex, and race as covariates. Results/Data Synthesis: Metabolic burden showed significant interaction with APOE-ε4 status that remained after covariate adjustment (β= -0.15, 95% CI [-0.32, -0.01], p< 0.05). Specifically, the influence of metabolic burden on cognition is worse among APOE-ε4 carriers. Nutritional deficit demonstrated significant interaction with APOE-ε4 status that became non-significant after covariate adjustment. Renal and glycemic burden showed significant negative main effects on cognition that similarly became non-significant after adjustment. Conclusions: Findings highlight that metabolic burden has an effect on cognition in older adults who have the APOE-ε4 genotype. This suggests that genetic risk may amplify the influence of metabolic dysregulation on cognition. While these findings suggest that maintaining metabolic health is necessary for preserving cognition, especially among APOE-ε4 carriers, replication studies in larger, longitudinal samples are warranted.