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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\u00a0h). 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.<\/jats:p>","DOI":"10.1007\/s11357-026-02323-7","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:36:14Z","timestamp":1779896174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epileptiform discharges in neurodegenerative diseases linked to atrophy but not associated with iron depositions"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-2910","authenticated-orcid":false,"given":"Christian Sand\u00f8e","family":"Musaeus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian Steen","family":"Frederiksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-220X","authenticated-orcid":false,"given":"Gunhild","family":"Waldemar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2105-6199","authenticated-orcid":false,"given":"Troels Wesenberg","family":"Kj\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark B.","family":"Vestergaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte Bo","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8478-8098","authenticated-orcid":false,"given":"Peter","family":"H\u00f8gh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen Gregers","family":"Hasselbalch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8628-8057","authenticated-orcid":false,"given":"Preben","family":"Kidmose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-8710","authenticated-orcid":false,"given":"Martin Christian","family":"Hemmsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike Lind","family":"Rank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-7749","authenticated-orcid":false,"given":"Henrik Bo Wiberg","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0004-6354","authenticated-orcid":false,"given":"Ulrich","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"2323_CR1","doi-asserted-by":"publisher","first-page":"e2259","DOI":"10.1212\/WNL.0000000000010612","volume":"95","author":"AD Lam","year":"2020","unstructured":"Lam AD, Sarkis RA, Pellerin KR, Jing J, Dworetzky BA, Hoch DB, et al. 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Brain. 2026;149:1058\u201369.","journal-title":"Brain"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02323-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-026-02323-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02323-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:02:18Z","timestamp":1779901338000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-026-02323-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":47,"alternative-id":["2323"],"URL":"https:\/\/doi.org\/10.1007\/s11357-026-02323-7","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"5 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Capital Region Ethics Committee (H-17035751) and by the Danish Medicines Agency (2017112288) and registered at the Data Protection Agency (P-2021-866). All participants gave written and oral informed consent before participating in the study. The study is registered at clinicaltrials.gov (NCT04436341).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have contributed to the work, agreed with the presented findings, and approved the version to be published.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CSM received an unrestricted grant from T&W Engineering. Two authors (Mike Lind Rank and Martin Christian Hemmsen) who are current or past employees of Cebreo Medical contributed to the interpretation and writing of the report. KF reports no competing interests. Outside the present work, KF reports the following disclosures: is or has been a member of advisory boards or acts or has acted as consultant for Eisai, Novo Nordisk, Roche Diagnostics, Eli-Lilly (remuneration paid to institution); has speaking engagement for Eisai\/BioArctic, Novo Nordisk (remuneration paid to institution), Dagens Medicin (personal remuneration); is or has been principal investigator in clinical trials sponsored by Biogen, Novo Nordisk, Roche, Roche Diagnostics (remuneration paid to institution); Editor-in-Chief Alzheimer\u2019s Research and Therapy (Springer\u2014Nature) (personal remuneration); and has received research funding from Aase og Ejner Danielsens Fond, Alzheimer Forskningsfonden, A.P. M\u00f8ller fonden, Beckett fonden, C2N, DANMODIS, Ellen M\u00f8rch Fonden, ERA-PERMED, Fonden for Neurologisk Forskning, Grosserer F.L.Foghts Fond, Harboefonden, Hertzfonden, IHI, Innovationsfonden, Jascha Fonden, KID fonden, Kong Christian den Tiendes Minde-fond, Overretssagf\u00f8rer L. Zeuthens Mindefond, Parkinsonforeningen, Rigshospitalets Forskningspulje.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}