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Studies have shown that 10%\u201325% of individuals with LoUE develop dementia within 3\u20134\u2009years following their first seizure. However, the mechanisms underlying progression from LoUE to dementia remain poorly understood. The goals of the ELUCID study are to identify risk factors associated with the development of cognitive decline and dementia in LoUE and to develop tools to identify patients at a high risk for these outcomes and thereby establish a foundation for dementia prevention strategies in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Analysis<\/jats:title>\n                    <jats:p>ELUCID is a multi\u2010center prospective longitudinal observational study that will enroll 600 participants aged 55 or older with LoUE across seven U.S. medical centers. Participants will undergo a baseline evaluation that includes a detailed clinical history, cognitive testing, brain MRI, overnight scalp EEG, and blood biomarkers. Participants will be followed at 6\u2010month intervals for up to 5\u2009years, to record cognitive and neurological changes, with the primary outcomes of interest being the development of mild cognitive impairment and\/or dementia. This study aims to establish LoUE disease subtypes based on biomarkers, cognitive trajectories, and imaging features and to develop a risk stratification tool for predicting cognitive decline and dementia in patients presenting with LoUE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and Dissemination<\/jats:title>\n                    <jats:p>ELUCID has obtained IRB approval (no. 2023P001566, August 2023), with the Mass General Brigham IRB serving as the single IRB of record. All de\u2010identified study data will be made publicly available on completion of the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:styled-content style=\"fixed-case\">ELUCID<\/jats:styled-content>\n                      study is a research project involving several medical centers across the U.S. It will focus on older adults who have recently developed seizures without a clear cause. Participants undergo an initial evaluation that includes questions about their medical history, a brain\n                      <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>\n                      , an overnight scalp\n                      <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\n                      (brain wave study), and a blood draw. They will be followed over time with health questionnaires and yearly tests of memory and thinking. The purpose of the study is to learn what factors increase the risk of dementia in this population and to develop tools to predict which individuals are at the highest risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70184","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T15:54:45Z","timestamp":1764431685000},"page":"363-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Late\u2010onset unexplained epilepsy as a risk factor for cognitive impairment and dementia: Protocol for a multi\u2010center prospective longitudinal observational study (\n                    <scp>ELUCID<\/scp>\n                    )"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7754-4637","authenticated-orcid":false,"given":"Alice D.","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6457-938X","authenticated-orcid":false,"given":"Emily L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-7864","authenticated-orcid":false,"given":"Rani A.","family":"Sarkis","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Brigham and Women\u2019s Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-6752","authenticated-orcid":false,"given":"Leah J.","family":"Blank","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-789X","authenticated-orcid":false,"given":"Tyler E.","family":"Gaston","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4531-1967","authenticated-orcid":false,"given":"Mouhsin M.","family":"Shafi","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-1723","authenticated-orcid":false,"given":"Rodrigo","family":"Zepeda","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas Southwestern  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4856-7602","authenticated-orcid":false,"given":"Kyle R.","family":"Pellerin","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-5866","authenticated-orcid":false,"given":"Nathalie","family":"Jette","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary Cumming School of Medicine  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-0155","authenticated-orcid":false,"given":"Douglas N.","family":"Greve","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Athinoula A. 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