A-142: Independent and Interactive Effects of Brain Iron and White Matter Hyperintensity Burden on Cognitive Performance in Older Adults From the ADNI Cohort
Abstract
Objective: We examined the independent and interactive associations of brain iron, measured using quantitative susceptibility mapping (QSM), and white matter hyperintensity (WMH) burden with cognition in older adults. We hypothesized that greater brain iron and WMH burden would predict poorer executive functioning and tested whether brain iron explained variance beyond vascular burden and whether WMH burden moderated iron–cognition associations. Method/Data Selection: Baseline data from 117 Alzheimer’s Disease Neuroimaging Initiative participants spanning normal cognition, mild cognitive impairment, and Alzheimer’s disease were analyzed using a cross-sectional design. Participants had QSM-derived brain iron estimates, T2-FLAIR-derived WMH measures, and composite scores of executive functioning and episodic memory. Pearson correlations and linear regressions adjusted for age, sex, education, and diagnostic group. Moderation and mediation analyses were conducted. Results/Data Synthesis: Greater WMH burden was significantly associated with poorer executive functioning and remained a significant predictor in adjusted regression models. Brain iron was not significantly associated with executive functioning or episodic memory and did not explain additional variance beyond WMH burden. The interaction between brain iron and WMH burden was nonsignificant, and exploratory mediation analyses did not support indirect effects on cognitive outcomes. Conclusions: WMH burden demonstrated a clearer association with executive functioning than brain iron. Brain iron provided no additional explanatory value beyond vascular burden, and the hypothesized interaction and indirect effects were not observed. These findings suggest that brain iron and WMH burden may operate independently in this dataset. Given the cross-sectional design and sample size, larger longitudinal studies are needed to clarify their contributions to cognitive aging.