{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:12:54Z","timestamp":1778026374998,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,1]]},"group-title":"Neurology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Brain structural differences consistent with an older-appearing brain have been reported in people with epilepsy, but the extent to which these differences reflect clinical characteristics vs broader socioeconomic context is unclear. We investigated whether country-level socioeconomic factors are associated with neuroanatomical differences in adults with epilepsy using MRI-based age prediction, along with epilepsy subtype, sex, and clinical factors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Structural MRI and clinical data were collected from 26 epilepsy centres across 12 countries in the Americas, Australia, Europe, Asia and Africa. MRI-based age estimates were estimated using a previously developed prediction model trained on 29,175 healthy subjects. Brain predicted age difference (BrainPAD) was calculated as the difference between MRI-predicted brain age and chronological age. National gross domestic product (GDP) per capita and income inequality (Gini index) were obtained from the World Bank. Associations between BrainPAD and epilepsy subtype (temporal lobe epilepsy, extratemporal epilepsy, and genetic generalised epilepsy), national socioeconomic context (GDP per capita and Gini index), age and sex were assessed using regression models.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We analyzed 2,109 individuals with epilepsy and 1,041 healthy non-epilepsy controls (57% female; median age = 35; range 17-83). BrainPAD was higher in epilepsy than controls (\u03b2 4.2 years, SE 0.4; t=10.6), with increases ranging from 2.5 to 6 years across subtypes. Male sex was associated with 1 year higher BrainPAD relative to females (SE 0.33, t=3.12). There were no main effects of GDP or Gini index; however, significant interactions between were observed. The effect of epilepsy on BrainPAD was greater in countries with lower GDP per capita (t=-2.74) and higher income inequality (t=2.72).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Clinical factors and socioeconomic context both influence brain structural ageing in epilepsy. These findings highlight the importance of geographic and economic diversity in neuroimaging research and underscore the relevance of global socioeconomic context when interpreting brain health measures.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.30.26352177","type":"posted-content","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:05:14Z","timestamp":1777676714000},"source":"Crossref","is-referenced-by-count":0,"title":["Global Socioeconomic Context and Brain Ageing in Epilepsy: an ENIGMA-Epilepsy study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-2167","authenticated-orcid":false,"given":"Heath R","family":"Pardoe","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jemima Robson","family":"Bbiomed","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Ireland","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Absil","sequence":"additional","affiliation":[{"name":"HUB H\u00f4pital Erasme - Radiology - MRI Unit, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-2393","authenticated-orcid":false,"given":"Andre","family":"Altmann","sequence":"additional","affiliation":[{"name":"UCL Hawkes Institute, Department of Medical Physics and Biomedical Engineering, UCL, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina KM","family":"Alvim","sequence":"additional","affiliation":[{"name":"Neuroimaging Laboratory, Department of Neurology, University of Campinas-UNICAMP, Campinas, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatello","family":"Arienzo","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences & Psychiatry, University of California San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Ballerini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Barbi","sequence":"additional","affiliation":[{"name":"Neuroscience and Human Genetics Department, Meyer Children\u2019s Hospital IRCCS, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurosciences, IRCCS Foundation Stella Maris, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-6214","authenticated-orcid":false,"given":"Tobias","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, University Hospital Bonn, Bonn, Germany"},{"name":"Department of Epileptology, University Hospital Bonn, Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-6041","authenticated-orcid":false,"given":"Boris","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Blackmon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA"},{"name":"Department of Population Health, Aga Khan University, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E.Medea, Epilepsy and Clinical Neurophysiology Unit, Conegliano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of South Carolina School of Medicine, Columbia, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bosco","sequence":"additional","affiliation":[{"name":"IRCCS Stella Maris Foundation, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Bunyamin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Eugenia","family":"Caligiuri","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d of 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Melbourne, VIC, Australia"},{"name":"Austin Hospital, Heidelberg, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa"},{"name":"Centre for Global Epilepsy, Oxford University, Oxford, UK"},{"name":"Clinical Epilepsy Research Group, Neuroscience Institute, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Jahanshad","sequence":"additional","affiliation":[{"name":"Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-3205","authenticated-orcid":false,"given":"Jonathan K","family":"Kleen","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4604-3367","authenticated-orcid":false,"given":"Raviteja","family":"Kotikalapudi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University Center G\u00f6ttingen, G\u00f6ttingen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Universit\u00e4tsmedizin Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad Zakaria","family":"Koubeissi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation Medicine, George Washington University, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Labate","sequence":"additional","affiliation":[{"name":"Neurology 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