{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:07Z","timestamp":1792790407602,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Neuroscience","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging","award":["R01AG071566"],"award-info":[{"award-number":["R01AG071566"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["R01AG074392"],"award-info":[{"award-number":["R01AG074392"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["P30AG072959"],"award-info":[{"award-number":["P30AG072959"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences","award":["P20GM109025"],"award-info":[{"award-number":["P20GM109025"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Blood\u2013based Alzheimer\u2019s disease (AD) biomarkers provide scalable detection of AD pathology, yet their relationships with hippocampal\u2013dependent mnemonic discrimination remain unclear. This study examined how object mnemonic discrimination relates to age, hippocampal structure, and plasma AD biomarkers in cognitively normal (CN) older adults and individuals with amnestic mild cognitive impairment (aMCI).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Forty\u2013six CN and forty\u2013one aMCI participants completed an object mnemonic similarity task (MST). Mnemonic discrimination was quantified using the overall lure discrimination index (LDI) and similarity\u2013specific LDIs. Plasma pTau181, pTau217, pTau231, and GFAP were assayed, and hippocampal volumes were derived from 7T MR scanner. Multiple linear regression models assessed associations between LDI and biomarkers, controlling for age, sex, education, APOE4 status, and diagnosis. Repeated\u2013measures ANCOVA and linear mixed effects models evaluated similarity\u2013dependent age effects. ROC analyses and stepwise logistic regression quantified diagnostic classification performance.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>LDI was significantly reduced in aMCI compared to CN. Total hippocampal volume and plasma pTau217 showed the strongest associations with LDI, exceeding those of pTau181, pTau231, and GFAP. LDI discriminated aMCI from CN with high accuracy (AUC = 0.836), comparable to hippocampal volume and plasma biomarkers. A combined model including LDI, pTau181, pTau217, and hippocampal volume achieved the highest diagnostic accuracy (AUC = 0.931). Age effects were similarity\u2013dependent: discrimination declined with age only for low\u2013similarity lures, independent of diagnosis. Sex differences emerged within aMCI, with females showing lower LDI than males.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Object mnemonic discrimination provides a sensitive behavioral marker linked to hippocampal volume and plasma pTau217, showing discriminative power comparable to established AD biomarkers in separating aMCI from CN participants. Similarity\u2013dependent age effects highlight age-related deficits are not universal for lures with varying similarity levels.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.14.750966","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:00:22Z","timestamp":1789675222000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of object mnemonic discrimination deficit with age and AD biomarkers in older adults"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-9680","authenticated-orcid":false,"given":"Zhengshi","family":"Yang","sequence":"first","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn M.","family":"Bekris","sequence":"additional","affiliation":[{"name":"Dept. of Laboratory Medicine & Pathology, School of Medicine, University of Washington, Seattle, 98104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Khrestian","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, OH, 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Koenig","sequence":"additional","affiliation":[{"name":"Imaging Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Curran","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Nandy","sequence":"additional","affiliation":[{"name":"Biostatistics, University of North Texas, Health Sciences Center, Fort Worth, Texas, 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithran Pattiam","family":"Giriprakash","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chendi","family":"Han","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagan","family":"Pillai","sequence":"additional","affiliation":[{"name":"Cleveland Clinic, Cleveland, OH, 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fox","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Imaging Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Cordes","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA"},{"name":"Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092112250848000_2026.09.14.750966v1.1","doi-asserted-by":"publisher","DOI":"10.12865\/CHSJ.50.02.02"},{"key":"2026092112250848000_2026.09.14.750966v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22562"},{"key":"2026092112250848000_2026.09.14.750966v1.3","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3233\/JAD-230221","article-title":"Mnemonic Discrimination Performance in a Memory Clinic: A Pilot Study","volume":"94","year":"2023","journal-title":"J Alzheimers Dis"},{"key":"2026092112250848000_2026.09.14.750966v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2019.08.003"},{"key":"2026092112250848000_2026.09.14.750966v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22162"},{"key":"2026092112250848000_2026.09.14.750966v1.6","doi-asserted-by":"crossref","first-page":"7572","DOI":"10.1038\/s41598-020-64595-z","article-title":"Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: A 7\u25a1T imaging study","volume":"10","year":"2020","journal-title":"Scientific Reports"},{"key":"2026092112250848000_2026.09.14.750966v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/alz.095462"},{"key":"2026092112250848000_2026.09.14.750966v1.8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13024-023-00605-8","article-title":"Plasma phospho-tau in Alzheimer\u2019s disease: towards diagnostic and therapeutic trial applications","volume":"18","year":"2023","journal-title":"Molecular Neurodegeneration"},{"key":"2026092112250848000_2026.09.14.750966v1.9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s13195-023-01340-4","article-title":"Clinical and biological relevance of glial fibrillary acidic protein in Alzheimer\u2019s disease","volume":"15","year":"2023","journal-title":"Alzheimer\u2019s Research & Therapy"},{"key":"2026092112250848000_2026.09.14.750966v1.10","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000401"},{"key":"2026092112250848000_2026.09.14.750966v1.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425"},{"key":"2026092112250848000_2026.09.14.750966v1.12","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jalz.2019.04.001","article-title":"Duration of preclinical, prodromal, and dementia stages of Alzheimer\u2019s disease in relation to age, sex, and APOE genotype","volume":"15","year":"2019","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026092112250848000_2026.09.14.750966v1.13","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.1002\/alz.13844","article-title":"Sex and gender differences in cognitive resilience to aging and Alzheimer\u2019s disease","volume":"20","author":"for the Reserve R, Protective Factors Professional Interest Area S, area GPI, Group tASI","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026092112250848000_2026.09.14.750966v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2012.12.014"},{"key":"2026092112250848000_2026.09.14.750966v1.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101567108"},{"key":"2026092112250848000_2026.09.14.750966v1.16","doi-asserted-by":"crossref","unstructured":"Yang Z , Zhuang X , Koenig KA , Leverenz JB , Curran T , Lowe MJ , Cordes D (2024) Pattern separation involves regions beyond the hippocampus in non-demented elderly individuals: A 7T object lure task fMRI study. Imaging Neuroscience 2.","DOI":"10.1162\/imag_a_00404"},{"key":"2026092112250848000_2026.09.14.750966v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20808"},{"key":"2026092112250848000_2026.09.14.750966v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.06.049"},{"key":"2026092112250848000_2026.09.14.750966v1.19","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1093\/geronb\/gbad091","article-title":"Executive Function Predicts Older Adults\u2019 Lure Discrimination Difficulties on the Mnemonic Similarity Task","volume":"78","year":"2023","journal-title":"The Journals of Gerontology: Series B"},{"key":"2026092112250848000_2026.09.14.750966v1.20","doi-asserted-by":"publisher","DOI":"10.1101\/lm.049197.118"},{"key":"2026092112250848000_2026.09.14.750966v1.21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.media.2017.09.006","article-title":"Segmenting hippocampal subfields from 3T MRI with multi-modality images","volume":"43","year":"2018","journal-title":"Med Image Anal"},{"key":"2026092112250848000_2026.09.14.750966v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.23073"},{"key":"2026092112250848000_2026.09.14.750966v1.23","first-page":"64","article-title":"Human neuroimaging studies on the hippocampal CA3 region\u2013integrating evidence for pattern separation and completion","volume":"8","year":"2014","journal-title":"Frontiers in cellular neuroscience"},{"key":"2026092112250848000_2026.09.14.750966v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-12148-5"},{"key":"2026092112250848000_2026.09.14.750966v1.25","doi-asserted-by":"crossref","unstructured":"Sim MA , Rowsthorn E , O\u2019Brien WT , Sun M , Cribb L , Franks K , McDonald SJ , Yiallourou S , Cavuoto M , Harding IH , Chong TTJ , Law M , O\u2019Brien TJ , Vivash L , Pase MP (2025) Plasma phosphorylated tau-217 correlates with brain atrophy, cognition, and cerebrospinal fluid biomarkers in a cognitively healthy community cohort. Brain Communications 7.","DOI":"10.1093\/braincomms\/fcaf383"},{"key":"2026092112250848000_2026.09.14.750966v1.26","doi-asserted-by":"crossref","unstructured":"Sundermann EE , Banks SJ , Bondi MW , Martinez MA , Biegon A , Rotblatt LJ , Hildebrandt T (2026) Sex differences in the relationship of biomarker change to memory decline in early Alzheimer\u2019s disease: an observational cohort study. Biol Sex Differ 17.","DOI":"10.1186\/s13293-025-00820-6"},{"key":"2026092112250848000_2026.09.14.750966v1.27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1001\/jamaneurol.2025.0013","article-title":"Sex Differences in Longitudinal Tau-PET in Preclinical Alzheimer Disease: A Meta-Analysis","volume":"82","year":"2025","journal-title":"JAMA Neurol"},{"key":"2026092112250848000_2026.09.14.750966v1.28","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/jamaneurol.2026.0054","article-title":"Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E \u03b54 in an Admixed Autopsy Sample","volume":"83","year":"2026","journal-title":"JAMA Neurol"},{"key":"2026092112250848000_2026.09.14.750966v1.29","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03830-w"},{"key":"2026092112250848000_2026.09.14.750966v1.30","doi-asserted-by":"crossref","first-page":"100146","DOI":"10.1016\/j.nbas.2025.100146","article-title":"Sex differences in the association between episodic memory residual reserve index and change in executive function","volume":"8","year":"2025","journal-title":"Aging Brain"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.14.750966","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:25:20Z","timestamp":1790018720000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.14.750966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":30,"URL":"https:\/\/doi.org\/10.64898\/2026.09.14.750966","relation":{},"subject":[],"published":{"date-parts":[[2026,9,17]]},"subtype":"preprint"}}