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

OBJECTIVE: To test the hypothesis that the combination of elevated global β-AMYLOID (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 with florbetapir (18)F PET to obtain Aβ 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 MRIs were segmented to measure medial temporal lobe (MTL) volumes. Analyses were conducted using mixed-effects models with MTL ROI as a within-participant factor; age, iron content, and Aβ as between-participant factors; and MTL volumes (ERC and 3 hippocampal subfield regions) as the dependent variable. RESULTS: The model indicated a significant 4-way interaction among age, iron, Aβ, and MTL region. Post hoc analyses indicated that the 3-way interaction among age, Aβ, and iron content was selective to the ERC (β = −3.34, standard error = 1.33, 95% confidence interval −5.95 to −0.72), whereas a significant negative association between age and ERC volume was present only 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 and the potential role for iron as an important contributor to the earliest, preclinical stages of pathologic aging.