{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:34:52Z","timestamp":1781314492396,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007321","name":"Finding A Cure for Epilepsy and Seizures","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Late\u2010onset epilepsy has the highest incidence among all age groups affected by epilepsy and often occurs in the absence of known clinical risk factors such as stroke and dementia. There is increasing evidence that brain changes contributing to epileptogenesis likely start years before disease onset, and we aim to relate cognitive and imaging correlates of subclinical brain injury to incident late\u2010onset epilepsy in a large, community\u2010based cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied Offspring Cohort of the Framingham Heart Study participants 45\u2009years or older, who were free of prevalent stroke, dementia, or epilepsy, and had neuropsychological (NP) evaluation and brain magnetic resonance imaging (MRI). Cognitive measures included Visual Reproduction Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making Test B minus A (TrTB\u2013TrTA; attention and executive function), and a global measure of cognition derived from principal component analysis. MRI measures included total cerebral brain volume, cortical gray matter volume (CGMV), white matter hyperintensity volume (WMHV), and hippocampal volume. Incident epilepsy was identified through a review of administrative data and medical records. Cox proportional hazards regression models were used for the analyses. All analyses were adjusted for age, sex, and educational level (cognition only).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among participants who underwent NP testing (<jats:italic>n<\/jats:italic>\u2009=\u20092349, 45.81% male), 31 incident epilepsy cases were identified during follow\u2010up. Better performance on the TrTB\u2013TrTA was associated with a lower risk of developing epilepsy (hazard ratio [HR] .25, 95% confidence interval [CI] .08\u2013.73; <jats:italic>p<\/jats:italic>\u2009=\u2009.011). In the subgroup of participants with MRI (<jats:italic>n<\/jats:italic>\u2009=\u20092056, 46.01% male), 27 developed epilepsy. Higher WMHV was associated with higher epilepsy risk (HR 1.5, 95%CI 1.01\u20132.20; <jats:italic>p<\/jats:italic>\u2009=\u2009.042), but higher CGMV (HR .73, 95% CI .57\u2013.93; <jats:italic>p<\/jats:italic>\u2009=\u2009.001) was associated with lower incidence of epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Better performance on the (TrTB\u2013TrTA), a measure of executive function and attention, and higher cortical volumes are associated with lower risk of developing epilepsy. Conversely, higher WMHV, a measure of occult vascular injury, increases the risk. Our study shows that non\u2010invasive tests performed in mid\u2010life may help identify people at risk for developing epilepsy later in life.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18160","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T12:05:41Z","timestamp":1731931541000},"page":"160-169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association of cognitive and structural correlates of brain aging and incident epilepsy. The Framingham Heart Study"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6276-0924","authenticated-orcid":false,"given":"Maria","family":"Stefanidou","sequence":"first","affiliation":[{"name":"Framingham Heart Study  Framingham Massachusetts USA"},{"name":"Department of Neurology Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-9481","authenticated-orcid":false,"given":"Jayandra J.","family":"Himali","sequence":"additional","affiliation":[{"name":"Framingham Heart Study  Framingham Massachusetts USA"},{"name":"Department of Neurology Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"Department of Biostatistics Boston University School of Public Health  Boston Massachusetts USA"},{"name":"Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Science Center  San Antonio Texas USA"},{"name":"Department of Population Health Sciences University of Texas Health Science Center  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Bernal","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences University of Texas Health Science Center  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Satizabal","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health Science Center  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Department of Neurology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R.","family":"Romero","sequence":"additional","affiliation":[{"name":"Framingham Heart Study  Framingham Massachusetts USA"},{"name":"Department of Neurology Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[{"name":"Framingham Heart Study  Framingham Massachusetts USA"},{"name":"Department of Neurology Boston University Chobanian and Avedisian School of Medicine  Boston Massachusetts USA"},{"name":"Department of Biostatistics Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"Framingham Heart Study  Framingham Massachusetts USA"},{"name":"Department of Neurology Boston University Chobanian 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