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Epileptiform discharges in neurodegenerative diseases linked to atrophy but not associated with iron depositions

Christian Sandøe Musaeus; Kristian Steen Frederiksen; Gunhild Waldemar; Troels Wesenberg Kjær; Mark B. Vestergaard; Birgitte Bo Andersen; Peter Høgh; Steen Gregers Hasselbalch; Preben Kidmose; Martin Christian Hemmsen; Mike Lind Rank; Henrik Bo Wiberg Larsson; Ulrich Lindberg
GeroScience · 2026

Abstract

Epileptiform discharges in Alzheimer’s disease (AD) and Lewy body dementia (DLB) may be associated with cognitive decline. Iron accumulation has been implicated in neurodegenerative processes; however, its relationship to epileptiform discharges remains unknown. In addition, the relationship between iron deposition, structural brain changes, and epileptiform discharges remains unclear. The objective is to investigate whether iron deposition and structural brain atrophy are associated with epileptiform discharges in patients with AD, DLB, and healthy controls (HCs). A total of 25 patients with AD, 10 patients with DLB, and 15 HCs were included in the analysis. The participants underwent MRI including quantitative susceptibility mapping (QSM) and structural T1-weighted imaging. We examined the four regions of interest, which are tied to iron deposition and AD pathology. Ear-EEG recordings were used to quantify spike frequency (epileptiform discharges/24 h). No significant group differences were found for susceptibility across regions. Susceptibility was not associated with spike frequency. Patients with AD exhibited significant hippocampal atrophy. Higher hippocampal volume was associated with lower spike rates in adjusted models. Susceptibility and hippocampal volume were associated, and in a multilinear model with age, hippocampal volume accounted for a larger proportion of the explained variance. This study found no evidence linking iron deposition to epileptiform discharges in AD or DLB. Instead, hippocampal atrophy appears more strongly associated with epileptiform discharges, which could indicate that the underlying pathological processes rather than iron are the primary driving factor for epileptiform discharges.

Bibliographic Information

JournalGeroScience
PublisherSpringer
Publication Date2026-05-27
Publication Year2026
Document TypeJournal Article
eISSN2509-2723
DOI10.1007/s11357-026-02323-7

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NARA Access Coverage1978-01-01~Current
Journal Homepagehttps://www.springer.com/journal/11357
Publisher PageOpen Publisher Page
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