Introduction: The entorhinal cortex (EC)-hippocampus system is critical for memory and affected early in Alzheimer's disease (AD). Cognitive dysfunction in AD is linked to neuropathological changes, including non-heme iron accumulation in vulnerable brain regions. This study characterized iron distribution in the EC-hippocampus system using ultra-high field (UHF) magnetic resonance imaging (MRI) at 7 Tesla (T) in aging and mild cognitive impairment (MCI), an AD at-risk state.

Methods: 40 participants (mean age [SD] 69.2 [7.42] years; 12 mild cognitive impairment (MCI), 28 cognitively healthy controls (HC)) underwent UHF MRI at 7 T with turbo spin echo and quantitative susceptibility mapping (QSM). Gray matter segmentation was performed using FreeSurfer software. Intraclass correlation coefficients (ICCs) were calculated for hippocampal and EC measures.

Results: ICCs for mean susceptibilities were 0.61 overall, 0.58 for HC, and 0.69 for MCI, with significant group differences between HC and MCI (Kolmogorov-Smirnov test, k  = 0.625, p  ≤ 0.05).

Discussion: Our findings suggest a higher coherence of non-heme iron distribution in MCI. An increasingly uniform distribution of iron in MCI could reflect a clinical continuum ranging from healthy aging to pathologic brain change and cognitive disorder. This highlights the potential of non-heme iron as a biomarker for early AD co-pathology.