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. 2025 Jul 2:17:1598859.
doi: 10.3389/fnagi.2025.1598859. eCollection 2025.

Hippocampal iron patterns in aging and mild cognitive impairment

Sonja M Kagerer  1   2   3 , Laetitia Vionnet  4 , Jiri M G van Bergen  1 , Rafael Meyer  1 , Anton F Gietl  1   2 , Klaas P Pruessmann  4 , Christoph Hock  1   5 , Paul G Unschuld  3   6
Affiliations

Hippocampal iron patterns in aging and mild cognitive impairment

Sonja M Kagerer et al. Front Aging Neurosci. .

Abstract

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.

Keywords: 7 tesla; QSM; entorhinal cortex; hippocampus subfields; iron; mild cognitive impairment; real-time field control; ultra-high field MRI.

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Conflict of interest statement

PU serves as a consultant for Eli Lilly and company, which is in accordance with HUG rules of compliance. Within the past five years AG received honoraria as speaker or advisor from Eli Lilly, Biogen AG and OM Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Field control set-up. 16 Fluorine field probes measure the field every 120 ms. After processing by the spectrometer, the controller estimates the required shim inputs that maintains the field to the target and actuates the gradients and shims amplifiers.
Figure 2
Figure 2
Image quality of 3D GRE T2* images with and without field control. Axial view of 3D GRE T2* images of one CN subject without (a) and with (b) real-time field control: typical artifacts due to field fluctuations are removed in (b).
Figure 3
Figure 3
Spatial definition of hippocampal subfields by 7 Tesla high-resolution coronal turbo spin echo (TSE) sequences. Coronal view of left and right hippocampal regions of high resolution 7 Tesla TSE images of one HC (1a–1c) with overlay of subfield segmentation by using FreeSurfer V6.0 (2a–2c). Slices are depicted from left to right from anterior to posterior.
Figure 4
Figure 4
Susceptibility distribution pattern of QSM values (ppm) in all subfields in HC and MCI participants. Scatterplot of QSM values (ppm) for all participants and all analyzed hippocampal subfields and the entorhinal cortex. Intraclass correlation coefficients were high for all (0.61), HC (0.58) and MCI (0.69) participants. Two-sample Kolmogorov–Smirnov test showed a significant difference between MCI and HC participants iron distribution (p = 0.049). CA, cornu ammonis; GCDG, granule cell layer of dentate gyrus.
See this image and copyright information in PMC

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