Contribution of iron and Aβ to age differences in entorhinal and hippocampal subfield volume.

Objective: To test the hypothesis that the combination of both elevated global Aβ burden and greater striatal iron content would be associated with smaller entorhinal cortex (ERC) volume, but not hippocampal subfield volumes, we measured volume and iron content using high resolution MRI and Aβ using PET imaging in a cross-sectional sample of 70 cognitively normal older adults. Methods: Participants were scanned using Florbetapir 18F PET to obtain amyloid-beta standardized uptake value ratios. Susceptibility-weighted MRI was collected and processed to yield R2* images and striatal regions-of-interest (ROIs) were manually placed to obtain a measure of striatal iron burden. Ultra-high-resolution T2/PD weighted MR images were segmented to measure MTL volumes. Analyses were conducted using mixed-effects models with MTL ROI as a within-subject factor and age, iron content, and Aβ as between-subjects factors and MTL volumes (ERC and three hippocampal subfield regions) as the dependent variable. Results: The model indicated a significant four-way interaction among age, iron, Aβ, and MTL region. Post-hoc analyses indicated the three-way interaction among age, Aβ, and iron content was selective to the ERC (β = -3.34, SE = 1.33, 95%CI[-5.95, -0.72]), where a significant negative association between age and ERC volume was only present in individuals with both elevated iron content and Aβ. Conclusions: These findings highlight the importance of studying Aβ in the context of other, potentially synergistic age-related brain factors, such as iron accumulation, as well as highlighting the potential role for iron as an important contributor to the earliest, preclinical stages of pathological aging.