{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:13:57Z","timestamp":1791994437016,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In light of the growing interest in the bidirectional relationship between epilepsy and dementia, this review aims to provide an overview of the role of hyperphosphorylated tau (pTau) in cognition in human epilepsy. A literature search identified five relevant studies. All of them examined pTau burden in surgical biopsy specimens from patients with temporal lobe epilepsy. The prevalence of pTau reported across the five studies, encompassing a total of 142 patients, ranged from 3.5% to 95%. Findings also varied regarding the location of pTau in the hippocampus and\/or temporal cortex. Two of five studies (40%) demonstrated an inverse relationship between pTau burden and cognitive performance, one study with regard to executive functions and the other with regard to naming and verbal short-term memory. The only longitudinal study found a significant link between pTau and cognitive decline in verbal learning and memory, and in part also in naming, from the pre- to the postoperative assessment and from three to 12 months postoperatively. Given the heterogeneity of the study cohorts and the neuropsychological and neuropathological methodologies and findings, no clear picture emerges regarding the association between pTau and cognition in temporal lobe epilepsy. Added to this is the multifactorial etiology of cognitive impairment in epilepsy, including the active epilepsy, the underlying and sometimes dynamic pathology, and anti-seizure medication. Some of these factors may affect pTau expression. Further research should aim to investigate pTau longitudinally and noninvasively on a whole-brain level, using targeted neuropsychological outcome measures and controlling for age and other factors potentially influencing cognitive trajectories in epilepsy.<\/jats:p>","DOI":"10.3390\/jcm14020514","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T04:42:08Z","timestamp":1736916128000},"page":"514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hyperphosphorylated Tau and Cognition in Epilepsy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5640-2592","authenticated-orcid":false,"given":"Juri-Alexander","family":"Witt","sequence":"first","affiliation":[{"name":"Department of Epileptology, University Hospital Bonn (UKB), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Andernach","sequence":"additional","affiliation":[{"name":"Department of Epileptology, University Hospital Bonn (UKB), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2661-3705","authenticated-orcid":false,"given":"Albert","family":"Becker","sequence":"additional","affiliation":[{"name":"Section for Translational Epilepsy Research, Institute of Neuropathology, Medical Faculty, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Helmstaedter","sequence":"additional","affiliation":[{"name":"Department of Epileptology, University Hospital Bonn (UKB), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1093\/brain\/awy022","article-title":"Cognition and Dementia in Older Patients with Epilepsy","volume":"141","author":"Sen","year":"2018","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez, M., Garc\u00eda-Cabrero, A., S\u00e1nchez-Elexpuru, G., Burgos, D., and Serratosa, J. (2018). Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041092"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hickman, L.B., Stern, J.M., Silverman, D.H.S., Salamon, N., and Vossel, K. (2023). Clinical, Imaging, and Biomarker Evidence of Amyloid- and Tau-Related Neurodegeneration in Late-Onset Epilepsy of Unknown Etiology. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1241638"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hwang, K., Vaknalli, R.N., Addo-Osafo, K., Vicente, M., and Vossel, K. (2022). Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.903973"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1093\/brain\/aww187","article-title":"Hyperphosphorylated Tau in Patients with Refractory Epilepsy Correlates with Cognitive Decline: A Study of Temporal Lobe Resections","volume":"139","author":"Tai","year":"2016","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/brain\/awz381","article-title":"Alzheimer-like Amyloid and Tau Alterations Associated with Cognitive Deficit in Temporal Lobe Epilepsy","volume":"143","author":"Gourmaud","year":"2020","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1111\/epi.17086","article-title":"Low Prevalence of Amyloid and Tau Pathology in Drug-Resistant Temporal Lobe Epilepsy","volume":"62","author":"Silva","year":"2021","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1007\/s12035-022-03190-x","article-title":"Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: A Neuropathological and Cognitive Study","volume":"60","author":"Toscano","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/epi4.12744","article-title":"Assessment of Tau Phosphorylation and \u03b2-Amyloid Pathology in Human Drug-Resistant Epilepsy","volume":"8","author":"Aroor","year":"2023","journal-title":"Epilepsia Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bandl.2018.12.007","article-title":"Knowledge of Language Function and Underlying Neural Networks Gained from Focal Seizures and Epilepsy Surgery","volume":"189","author":"Drane","year":"2019","journal-title":"Brain Lang."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1076\/jcen.21.6.784.853","article-title":"Short-Term Memory Deficit after Focal Parietal Damage","volume":"21","author":"Markowitsch","year":"1999","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neuroscience.2005.09.018","article-title":"The Functional Neuroanatomy of Working Memory: Contributions of Human Brain Lesion Studies","volume":"139","author":"Knight","year":"2006","journal-title":"Neuroscience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1093\/brain\/awr209","article-title":"Neurofibrillary Tangle Pathology and Braak Staging in Chronic Epilepsy in Relation to Traumatic Brain Injury and Hippocampal Sclerosis: A Post-Mortem Study","volume":"134","author":"Thom","year":"2011","journal-title":"Brain A J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5232","DOI":"10.1002\/alz.13158","article-title":"On behalf on the AMYPAD consortium Longitudinal Amyloid and Tau PET Imaging in Alzheimer\u2019s Disease: A Systematic Review of Methodologies and Factors Affecting Quantification","volume":"19","author":"Bollack","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.braindev.2014.08.010","article-title":"Infantile Tauopathies: Hemimegalencephaly; Tuberous Sclerosis Complex; Focal Cortical Dysplasia 2; Ganglioglioma","volume":"37","author":"Sarnat","year":"2015","journal-title":"Brain Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1055\/s-0028-1109799","article-title":"Neuropsychologie Bei Epilepsie Teil II: Gibt Es Eine Gemeinsame Basis Zur Etablierung Diagnostischer Leitlinien?","volume":"77","author":"Witt","year":"2009","journal-title":"Fortschritte Neurol. Psychiatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/epi.13646","article-title":"Current Standards of Neuropsychological Assessment in Epilepsy Surgery Centers across Europe","volume":"58","author":"Vogt","year":"2017","journal-title":"Epilepsia"},{"key":"ref_18","unstructured":"Helmstaedter, C., Hermann, B., Lassonde, M., Kahane, P., and Arzimanoglou, A. (2011). Inquiry on Assessments across Epilepsy Centers in Different Countries. Neuropsychology in the Care of People with Epilepsy, John Libbey Eurotext."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107865","DOI":"10.1016\/j.yebeh.2021.107865","article-title":"Hazardous Employment of Invalid Measures for Cognitive Outcome Assessment: You Only See What Your Test Can Show You","volume":"117","author":"Witt","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.eplepsyres.2009.09.002","article-title":"Unique and Shared Validity of the \u201cWechsler Logical Memory Test\u201d, the \u201cCalifornia Verbal Learning Test\u201d, and the \u201cVerbal Learning and Memory Test\u201d in Patients with Epilepsy","volume":"87","author":"Helmstaedter","year":"2009","journal-title":"Epilepsy Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1017\/S1355617708080582","article-title":"Differential Neuropsychological Test Sensitivity to Left Temporal Lobe Epilepsy","volume":"14","author":"Loring","year":"2008","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Helmstaedter, C., and Witt, J.-A. (2012). Clinical Neuropsychology in Epilepsy: Theoretical and Practical Issues., Elsevier B.V.","DOI":"10.1016\/B978-0-444-52898-8.00036-7"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1002\/alz.13085","article-title":"The Multifactorial Etiology of Cognitive Deficits in Epilepsy and the Neuropathology of Mesial Temporal Lobe Epilepsy beyond Hyperphosphorylated Tau","volume":"19","author":"Witt","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/ana.26557","article-title":"Neuropathological Insights into Unexpected Cognitive Decline in Epilepsy","volume":"93","author":"Reimers","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1093\/brain\/awp182","article-title":"Chronic Temporal Lobe Epilepsy: A Neurodevelopmental or Progressively Dementing Disease?","volume":"132","author":"Helmstaedter","year":"2009","journal-title":"Brain A J. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/S0140-6736(99)03542-4","article-title":"The Phantom of Progressive Dementia in Epilepsy","volume":"354","author":"Helmstaedter","year":"1999","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Helmstaedter, C., Lutz, T., Wolf, V., and Witt, J.A. (2023). Prevalence of Dementia in a Level 4 University Epilepsy Center: How Big Is the Problem?. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1217594"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/2\/514\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:29:00Z","timestamp":1759919340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/2\/514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["jcm14020514"],"URL":"https:\/\/doi.org\/10.3390\/jcm14020514","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]}}}