{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:59:54Z","timestamp":1782514794911,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Semantic intrusion errors (SIEs) are associated with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). It is unknown whether accounting for maximum learning capacity still leads to an increase in SIEs when elevated plasma p-tau<jats:sub>217<\/jats:sub>, a biological indicator of underlying AD, is present.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred fifty-eight older adult participants completed the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive cognitive challenge test designed to elicit SIEs. Of these, 108 were clinically diagnosed with amnestic MCI (aMCI). Fifty-eight individuals met or exceeded a plasma p-tau<jats:sub>217<\/jats:sub> positivity of &amp;gt;<jats:italic>0.5<\/jats:italic>5 pg\/ml, while 50 individuals scored below this threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjusting for demographic covariates and maximum learning capacity, the aMCI p-tau<jats:sub>217<\/jats:sub>+ group evidenced more SIEs compared to aMCI p-tau<jats:sub>217<\/jats:sub>- on the first (list B1; <jats:italic>p<\/jats:italic> = 0.035) and second trials of the competing list (list B2; <jats:italic>p<\/jats:italic> = 0.006). Biological predictors such as <jats:italic>ApoE<\/jats:italic> \u03b54 status, higher p-tau<jats:sub>217<\/jats:sub>, and older age were predictors of an elevated number of SIEs [list B2: <jats:italic>F<\/jats:italic> (3,104) = 10.92; <jats:italic>p<\/jats:italic> = 0.001; <jats:italic>R<\/jats:italic> = 0.489)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Unlike previous studies that used amyloid PET or other plasma biomarkers, individuals with aMCI p-tau<jats:sub>217<\/jats:sub>+ evidenced more SIEs, even after adjusting for their initial learning capacity, a covariate that has not been studied previously. These findings support that SIEs are more prevalent in the presence of underlying AD pathology and occur independent of learning deficits.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1613694","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:30:48Z","timestamp":1753198248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Semantic intrusion errors differentiate between amnestic MCI who are plasma p-tau217+ from p-tau217- after adjusting for initial learning strength"],"prefix":"10.3389","volume":"16","author":[{"given":"Rosie E.","family":"Curiel Cid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vaillancourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Crocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Crenshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Remedios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breton M.","family":"Asken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idaly Velez","family":"Uribe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-en","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rosselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Adjouadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Marsiske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren W.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"DeKosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjan","family":"Duara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Loewenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1037\/neu0000883","article-title":"A review of novel cognitive challenge tests for the assessment of preclinical Alzheimer's disease","volume":"37","author":"Curiel Cid","year":"2023","journal-title":"Neuropsychology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3233\/JAD-160866","article-title":"Validation of the Spanish version of the LASSI-L for diagnosing mild cognitive impairment and Alzheimer's disease","volume":"56","author":"Mat\u00edas-Guiu","year":"2017","journal-title":"J Alzheimers Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3233\/JAD-170276","article-title":"Recovery from proactive semantic interference and MRI volume: a replication and extension study","volume":"59","author":"Loewenstein","year":"2017","journal-title":"J Alzheimers Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.3233\/JAD-160881","article-title":"Recovery from proactive semantic interference in mild cognitive impairment and normal aging: relationship to atrophy in brain regions vulnerable to Alzheimer's disease","volume":"56","author":"Loewenstein","year":"2017","journal-title":"J Alzheimers Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jpsychires.2021.08.033","article-title":"Changes in LASSI-L performance over time among older adults with amnestic MCI and amyloid positivity: a preliminary study","volume":"143","author":"Kitaigorodsky","year":"2021","journal-title":"J Psychiatr Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1191718","DOI":"10.3389\/fneur.2023.1191718","article-title":"LASSI-L detects early cognitive changes in pre-motor manifest Huntington's disease: a replication and validation study","volume":"14","author":"Sierra","year":"2023","journal-title":"Front Neurol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1097\/WNN.0000000000000329","article-title":"Using the LASSI-L to detect robust interference effects in premanifest Huntington disease","volume":"36","author":"Sierra","year":"2023","journal-title":"Cogn Behav Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3389\/fneur.2020.00309","article-title":"Memory impairment in relapsing-remitting multiple sclerosis using a challenging semantic interference task","volume":"11","author":"Matias-Guiu","year":"2020","journal-title":"Front Neurol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.jagp.2013.01.066","article-title":"An evaluation of deficits in semantic cueing and proactive and retroactive interference as early features of Alzheimer's disease","volume":"22","author":"Crocco","year":"2014","journal-title":"Am J Geriatr Psychiatry."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e976","DOI":"10.1212\/WNL.0000000000006128","article-title":"Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment","volume":"91","author":"Loewenstein","year":"2018","journal-title":"Neurology."},{"key":"B11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3233\/JAD-170604","article-title":"Comparison between FCSRT and LASSI-L to detect early stage Alzheimer's disease","volume":"61","author":"Matias-Guiu","year":"2018","journal-title":"J Alzheimers Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.3233\/JAD-170491","article-title":"Failure to recover from proactive semantic interference and abnormal limbic connectivity in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease","volume":"60","author":"S\u00e1nchez","year":"2017","journal-title":"J Alzheimers Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1037\/neu0000542","article-title":"Types of errors on a semantic interference task in mild cognitive impairment and dementia","volume":"33","author":"Torres","year":"2019","journal-title":"Neuropsychology."},{"key":"B14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1177\/1073191117691608","article-title":"Novel cognitive paradigms for the detection of memory impairment in preclinical Alzheimer's disease","volume":"25","author":"Loewenstein","year":"2018","journal-title":"Assessment."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S98","DOI":"10.1002\/alz.13453","article-title":"Amyloid and tau-PET in early-onset AD: baseline data from the longitudinal early-onset Alzheimer's Disease Study (LEADS)","volume":"19","author":"Cho","year":"2023","journal-title":"Alzheimers Dement"},{"key":"B16","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic accuracy of a plasma phosphorylated Tau 217 immunoassay for Alzheimer disease pathology","volume":"81","author":"Ashton","year":"2024","journal-title":"JAMA Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13195-020-00595-5","article-title":"Elecsys CSF biomarker immunoassays demonstrate concordance with amyloid-PET imaging","volume":"12","author":"Doecke","year":"2020","journal-title":"Alzheimers Res Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13195-023-01302-w","article-title":"Head-to-head comparison between plasma p-tau217 and flortaucipir-PET in amyloid-positive patients with cognitive impairment","volume":"15","author":"Mundada","year":"2023","journal-title":"Alzheimers Res Ther."},{"key":"B19","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/978-94-007-0753-5_690","article-title":"Clinical Dementia Rating Scale","volume-title":"Encyclopedia of Quality of Life and Well-Being Research","author":"Schmidt","year":"2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1192\/bjp.140.6.566","article-title":"A new clinical scale for the staging of dementia","volume":"140","author":"Hughes","year":"1982","journal-title":"Br J Psychiatr."},{"key":"B21","article-title":"Hopkins verbal learning test\u2013revised: professional manual","author":"Brandt","year":"2001","journal-title":"Psychol Assess Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1097\/WAD.0b013e318142774e","article-title":"The National Alzheimer's Coordinating Center (NACC) database: the uniform data set","volume":"21","author":"Beekly","year":"2007","journal-title":"Alzheimer Dis Assoc Disord."},{"key":"B23","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1017\/S1355617700677032","article-title":"Category fluency test: normative data for English-and Spanish-speaking elderly","volume":"6","author":"Acevedo","year":"2000","journal-title":"J Int Neuropsychol Soc."},{"key":"B24","first-page":"816","volume-title":"Wechsler Adult Intelligence Scale\u2013Fourth Edition (WAIS\u2013IV)","author":"Wechsler","year":"2008"},{"key":"B25","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2466\/pms.1958.8.3.271","article-title":"Validity of the Trail Making Test as an indicator of organic brain damage","volume":"8","author":"Reitan","year":"1958","journal-title":"Percept Mot Skills."},{"key":"B26","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1080\/13854040590945346","article-title":"Advantages and disadvantages of separate norms for African Americans","volume":"19","author":"Manly","year":"2005","journal-title":"Clin Neuropsychol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e12617","DOI":"10.1002\/dad2.12617","article-title":"Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults","volume":"16","author":"Asken","year":"2024","journal-title":"Alzheimers Dement"},{"key":"B29","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.jagp.2016.02.056","article-title":"A novel cognitive stress test for the detection of preclinical Alzheimer disease: discriminative properties and relation to amyloid load","volume":"24","author":"Loewenstein","year":"2016","journal-title":"Am J Geriatr Psychiatry."},{"key":"B30","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.dadm.2019.05.003","article-title":"A cognitive stress test for prodromal Alzheimer's disease: Multiethnic generalizability","volume":"11","author":"Curiel Cid","year":"2019","journal-title":"Alzheimers Dement."},{"key":"B31","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000512804","article-title":"Intrusion errors and progression of cognitive deficits in older adults with mild cognitive impairment and PreMCI states","volume":"50","author":"Crocco","year":"2021","journal-title":"Dement Geriatr Cogn Disord."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1336008","DOI":"10.3389\/fnagi.2024.1336008","article-title":"Different aspects of failing to recover from proactive semantic interference predicts rate of progression from amnestic mild cognitive impairment to dementia","volume":"16","author":"Curiel Cid","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","article-title":"FSL","volume":"62","author":"Jenkinson","year":"2012","journal-title":"Neuroimage."},{"key":"B34","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3233\/JAD-200790","article-title":"A brief version of the LASSI-L detects prodromal Alzheimer's disease states","volume":"78","author":"Crocco","year":"2020","journal-title":"J Alzheimers Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1006\/nimg.2002.1132","article-title":"Improved optimization for the robust and accurate linear registration and motion correction of brain images","volume":"17","author":"Jenkinson","year":"2002","journal-title":"Neuroimage."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2014.07.003","article-title":"The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET","volume":"11","author":"Klunk","year":"2015","journal-title":"Alzheimers Dement."},{"key":"B37","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13195-020-00587-5","article-title":"Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease","volume":"12","author":"Amadoru","year":"2020","journal-title":"Alzheimers Res Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jpsychires.2020.02.008","article-title":"A novel method of evaluating semantic intrusion errors to distinguish between amyloid positive and negative groups on the Alzheimer's disease continuum","volume":"124","author":"Curiel Cid","year":"2020","journal-title":"J Psychiatr Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3508","DOI":"10.1007\/s00259-022-05784-y","article-title":"Quantification of amyloid PET for future clinical use: a state-of-the-art review","volume":"49","author":"Pemberton","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B40","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/0278-2626(91)90088-P","article-title":"The occurrence of different intrusive errors in patients with Alzheimer's disease, multiple cerebral infarctions, and major depression","volume":"16","author":"Loewenstein","year":"1991","journal-title":"Brain Cogn."},{"key":"B41","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1080\/87565648909540427","article-title":"An analysis of intrusive error types in Alzheimer's disease and related disorders","volume":"5","author":"Loewenstein","year":"1989","journal-title":"Dev Neuropsychol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1159\/000516230","article-title":"False memory and Alzheimer's disease pathology in patients with amnestic mild cognitive impairment: a study with amyloid PET","volume":"11","author":"Choi","year":"2021","journal-title":"Dement Geriatr Cogn Dis Extra."},{"key":"B43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3233\/JAD-2009-0931","article-title":"False recognition correlates with amyloid-\u03b21\u201342 but not with total tau in cerebrospinal fluid of patients with dementia and mild cognitive impairment","volume":"16","author":"Hildebrandt","year":"2009","journal-title":"J Alzheimers Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1037\/neu0000413","article-title":"Word-list intrusion errors predict progression to mild cognitive impairment","volume":"32","author":"Thomas","year":"2018","journal-title":"Neuropsychology."},{"key":"B45","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1017\/S1041610220004007","article-title":"Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis","volume":"34","author":"Zheng","year":"2022","journal-title":"Int Psychogeriatr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1037\/neu0000945","article-title":"Vulnerability to semantic and phonological interference in normal aging and amnestic mild cognitive impairment (aMCI)","volume":"38","author":"Chasles","year":"2024","journal-title":"Neuropsychology."},{"key":"B47","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s13311-022-01192-0","article-title":"Salient cognitive paradigms to assess preclinical Alzheimer's disease","volume":"19","author":"Curiel Cid","year":"2022","journal-title":"Neurotherapeutics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1017\/S1355617710000676","article-title":"Interdependence of episodic and semantic memory: evidence from neuropsychology","volume":"16","author":"Greenberg","year":"2010","journal-title":"J Int Neuropsychol Soc."},{"key":"B49","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3233\/JAD-220754","article-title":"Neuropsychological, metabolic, and connectivity underpinnings of semantic interference deficits using the LASSI-L","volume":"90","author":"Valles-Salgado","year":"2022","journal-title":"J Alzheimers Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1007\/s00429-019-01945-2","article-title":"The cingulate cortex and limbic systems for emotion, action, and memory","volume":"224","author":"Rolls","year":"2019","journal-title":"Brain Struct Funct."},{"key":"B51","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4236\/aad.2024.131002","article-title":"The computerized LASSI-BC test versus the standard LASSI-L paper-and-pencil version in community-based-samples","volume":"13","author":"Curiel Cid","year":"2024","journal-title":"Adv Alzheimers Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3233\/JAD-220348","article-title":"Persistent failure to recover from proactive semantic interference on the cognitive stress test differentiates between amnestic mild cognitive impairment, pre-mild cognitive impairment, and cognitively unimpaired older adults","volume":"90","author":"Loewenstein","year":"2022","journal-title":"J Alzheimers Dis"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1613694\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:30:49Z","timestamp":1753198249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1613694\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":52,"alternative-id":["10.3389\/fneur.2025.1613694"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1613694","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]},"article-number":"1613694"}}