{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:04:56Z","timestamp":1783955096715,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011942","name":"'s Heeren Loo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011942","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n Adults with epilepsy and intellectual disabilities (IDs) may be at increased risk of dementia, but clinical evaluation is complex and use of conventional biomarkers is often considered too invasive. We explored abnormality of serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau\u2010217 (p\u2010tau217) in these adults, and their associations with clinical outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Serum biomarker levels were quantified with Single Molecule Array (Simoa) in 68 adults with co\u2010occurring epilepsy and ID at a median age of 52.0 (range 24\u201376) years. Levels were classified normal\/abnormal (>95th percentile) in comparison to reference data of age\u2010matched healthy controls (NfL, GFAP) or Alzheimer's disease (AD)\u2013specific cutoff (p\u2010tau217). Associations with age were assessed with correlations and segmented regression analyses. Associations with adaptive decline, suspected dementia, ID, epilepsy, antiseizure medication, comorbidity, and mortality were explored using chi\u2010square tests, Mann\u2013Whitney\n U<\/jats:italic>\n tests, log rank tests, and Cox regression analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n NfL levels were abnormal in 51.5%, GFAP in 63.2%, and p\u2010tau217 in 2.9%. Age\u2010corrected\n Z<\/jats:italic>\n \u2010scores of NfL were still significantly associated with age (\n r<\/jats:italic>\n \u2009=\u2009.31,\n p<\/jats:italic>\n \u2009=\u2009.01). Elevated NfL was associated with significant adaptive decline (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20097.20,\n p<\/jats:italic>\n \u2009=\u2009.007), suspected dementia (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200910.73,\n p<\/jats:italic>\n \u2009=\u2009.001), monthly seizure frequency (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20095.21,\n p<\/jats:italic>\n \u2009=\u2009.03), non\u2010early seizure onset (\n U<\/jats:italic>\n \u2009=\u2009281,\n p<\/jats:italic>\n \u2009<\u2009.001), carbamazepine use (\n \u03c7<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20094.38,\n p<\/jats:italic>\n \u2009=\u2009.04), and mortality (Log rank\n p<\/jats:italic>\n \u2009=\u2009.04; hazard ratio [HR]\n p<\/jats:italic>\n \u2009=\u2009.007). GFAP levels were significantly higher in severe ID (median\n Z<\/jats:italic>\n \u2009=\u20092.5) compared to mild ID (median\n Z<\/jats:italic>\n \u2009=\u20091.6) (\n U<\/jats:italic>\n \u2009=\u2009196,\n p<\/jats:italic>\n \u2009=\u2009.02). Having abnormal levels of GFAP and NfL simultaneously was the most common biomarker profile in participants with suspected dementia (69.2%).\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n NfL and GFAP were abnormal in many participants, coinciding with clinical decline. Findings are suggestive for ongoing neural injury, but not necessarily for AD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi.70218","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:41:58Z","timestamp":1774874518000},"page":"3494-3507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum\n NfL<\/scp>\n ,\n GFAP<\/scp>\n , and\n p\u2010tau217<\/scp>\n in adults with drug\u2010resistant epilepsy and intellectual disabilities: Signs of ongoing neural injury"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4957-5759","authenticated-orcid":false,"given":"Hadassa","family":"Kwetsie","sequence":"first","affiliation":[{"name":"Amsterdam Reproduction and Development, Emma Children's Hospital Amsterdam UMC Amsterdam The Netherlands"},{"name":"Advisium, 's Heeren Loo Zorggroep Amersfoort The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-7445","authenticated-orcid":false,"given":"Inge M. W.","family":"Verberk","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Neurodegeneration Amsterdam Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-4452","authenticated-orcid":false,"given":"Jans S.","family":"van Ool","sequence":"additional","affiliation":[{"name":"Department of Residential Care Kempenhaeghe Epilepsy Center Heeze The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke J. J.","family":"Rampen","sequence":"additional","affiliation":[{"name":"Department of Neurology Academic Center for Epileptology, Kempenhaeghe Epilepsy Center Heeze The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-7286","authenticated-orcid":false,"given":"Rebecca Z.","family":"Rousset","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Amsterdam Reproduction and Development, Emma Children's Hospital Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Child Neurology Amsterdam Leukodystrophy Center, Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-0720","authenticated-orcid":false,"given":"Dederieke A. M.","family":"Maes\u2010Festen","sequence":"additional","affiliation":[{"name":"Intellectual Disability Medicine, Department of General Practice Erasmus MC, University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-8337","authenticated-orcid":false,"given":"Clara D. M.","family":"van Karnebeek","sequence":"additional","affiliation":[{"name":"Amsterdam Reproduction and Development, Emma Children's Hospital Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam Gastroenterology Endocrinology and Metabolism Amsterdam University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Laboratory Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Neurodegeneration Amsterdam Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-1539","authenticated-orcid":false,"given":"Erik","family":"Boot","sequence":"additional","affiliation":[{"name":"Advisium, 's Heeren Loo Zorggroep Amersfoort The Netherlands"},{"name":"Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Institute (MHeNs) Maastricht University Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8149-8645","authenticated-orcid":false,"given":"Agnies M.","family":"van Eeghen","sequence":"additional","affiliation":[{"name":"Amsterdam Reproduction and Development, Emma Children's Hospital Amsterdam UMC Amsterdam The Netherlands"},{"name":"Advisium, 's Heeren Loo Zorggroep Amersfoort The 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