ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1598859
Hippocampal iron patterns in aging and mild cognitive impairment
Provisionally accepted
Sonja Maria Maria Kagerer1,2,3*
Laetitia Vionnet4Jiri van Bergen1Rafael Meyer1Anton Franz Gietl1,2Klaas Pruessmann4Christoph Hock1,5
Paul Gerson Unschuld3,6- 1Institute for Regenerative Medicine, Faculty of Medicine, University of Zurich, Zürich, Zürich, Switzerland
- 2Geriatric Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Zurich, Switzerland
- 3Department of Psychiatry, University of Geneva, Geneva, Switzerland
- 4Institute of Biomedical Engineering, ETH Zürich, Gloriastrasse, Zurich, Switzerland
- 5Neurimmune AG, Schlieren, Switzerland
- 6Geriatric Psychiatry Service, University Hospitals of Geneva, Geneva, Switzerland
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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 7T 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: ultra-high field MRI, 7 Tesla, QSM, Mild Cognitive Impairment, Hippocampus subfields, Entorhinal Cortex, Iron, real-time field control
Received: 24 Mar 2025; Accepted: 10 Jun 2025.
Copyright: © 2025 Kagerer, Vionnet, van Bergen, Meyer, Gietl, Pruessmann, Hock and Unschuld. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sonja Maria Maria Kagerer, Institute for Regenerative Medicine, Faculty of Medicine, University of Zurich, Zürich, 8952, Zürich, Switzerland
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