{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:46:14Z","timestamp":1785793574380,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,22]]},"group-title":"Neurology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Alzheimer\u2019s disease (AD) develops over a prolonged asymptomatic phase marked by silent pathology. Identifying cognitively unimpaired individuals likely to progress to mild cognitive impairment (MCI) is essential for early intervention. We investigated whether multimodal combinations of biomarkers, including frequency-specific neurophysiological activity, enhance prediction beyond demographic and genetic factors in older adults (n = 102; 31 progressors; mean follow-up = 5.9 years). Biomarkers included MEG-derived alpha power, MRI-derived hippocampal volume, plasma A\u03b242\/40 ratio and p-tau217, and neocortical A\u03b2 and entorhinal tau PET. Cox regression models estimated progression risk and tested time-varying prognostic effects. Neurophysiological and proteinopathy biomarkers improved prediction beyond clinical and genetic factors. Elevated alpha power predicted short-term risk, but its predictive value weakened over time, whereas high neocortical A\u03b2 became increasingly predictive with longer follow-up. Plasma A\u03b242\/40, p-tau217, and tau PET each conferred higher risk, while hippocampal volume did not. Findings support a multimodal, time-sensitive framework for individualized risk prediction in preclinical AD.<\/jats:p>","DOI":"10.1101\/2025.09.20.25336240","type":"posted-content","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:30:29Z","timestamp":1758587429000},"source":"Crossref","is-referenced-by-count":1,"title":["Prediction of mild cognitive impairment progression using time-sensitive multimodal biomarkers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-2352","authenticated-orcid":false,"given":"Jonathan","family":"Gallego-Rudolf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0917-1570","authenticated-orcid":false,"given":"Alex I.","family":"Wiesman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-7162","authenticated-orcid":false,"given":"Yara","family":"Yakoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-6763","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-5713","authenticated-orcid":false,"given":"Sylvain","family":"Baillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2338-0467","authenticated-orcid":false,"given":"Sylvia","family":"Villeneuve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PREVENT-AD Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025092411501337000_2025.09.20.25336240v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00645-6"},{"key":"2025092411501337000_2025.09.20.25336240v1.2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2022.0607"},{"key":"2025092411501337000_2025.09.20.25336240v1.3","first-page":"146","article-title":"\u00dcber eine eigenartige Erkrankung der Hirnrinde","volume":"64","year":"1907","journal-title":"Allgemeine Zeitschrift Fur Psychiatrie Und Phychish-Gerichtliche Medizin"},{"key":"2025092411501337000_2025.09.20.25336240v1.4","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006075"},{"key":"2025092411501337000_2025.09.20.25336240v1.5","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"2025092411501337000_2025.09.20.25336240v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12311"},{"key":"2025092411501337000_2025.09.20.25336240v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-020-04773-3"},{"key":"2025092411501337000_2025.09.20.25336240v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4504"},{"key":"2025092411501337000_2025.09.20.25336240v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.03.002"},{"key":"2025092411501337000_2025.09.20.25336240v1.10","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5847"},{"key":"2025092411501337000_2025.09.20.25336240v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2025092411501337000_2025.09.20.25336240v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00021-6"},{"key":"2025092411501337000_2025.09.20.25336240v1.13","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2016.121"},{"key":"2025092411501337000_2025.09.20.25336240v1.14","doi-asserted-by":"publisher","DOI":"10.1177\/15500594221072708"},{"key":"2025092411501337000_2025.09.20.25336240v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0687-6"},{"key":"2025092411501337000_2025.09.20.25336240v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"2025092411501337000_2025.09.20.25336240v1.17","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0b013e31817da184"},{"key":"2025092411501337000_2025.09.20.25336240v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.021"},{"key":"2025092411501337000_2025.09.20.25336240v1.19","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009240"},{"key":"2025092411501337000_2025.09.20.25336240v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.002"},{"key":"2025092411501337000_2025.09.20.25336240v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.07.004"},{"key":"2025092411501337000_2025.09.20.25336240v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"2025092411501337000_2025.09.20.25336240v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01763-8"},{"key":"2025092411501337000_2025.09.20.25336240v1.24","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00100"},{"key":"2025092411501337000_2025.09.20.25336240v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(84)80190-4"},{"key":"2025092411501337000_2025.09.20.25336240v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25492-9"},{"key":"2025092411501337000_2025.09.20.25336240v1.27","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00605-8"},{"key":"2025092411501337000_2025.09.20.25336240v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.10.001"},{"key":"2025092411501337000_2025.09.20.25336240v1.29","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179935"},{"key":"2025092411501337000_2025.09.20.25336240v1.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"2025092411501337000_2025.09.20.25336240v1.31","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.140.6.566"},{"key":"2025092411501337000_2025.09.20.25336240v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"2025092411501337000_2025.09.20.25336240v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"2025092411501337000_2025.09.20.25336240v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"2025092411501337000_2025.09.20.25336240v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad057"},{"key":"2025092411501337000_2025.09.20.25336240v1.36","unstructured":"Kassambara, A. , Kosinski, M. , Biecek, P. , & Fabian, S. (2024). Survminer: Drawing survival curves using \u201cggplot2\u201d (Version 0.5.0) [Computer software]. https:\/\/rpkgs.datanovia.com\/survminer\/index.html"},{"key":"2025092411501337000_2025.09.20.25336240v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.03.034"},{"key":"2025092411501337000_2025.09.20.25336240v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/srep37685"},{"key":"2025092411501337000_2025.09.20.25336240v1.39","doi-asserted-by":"publisher","DOI":"10.1142\/S0129065717500411"},{"key":"2025092411501337000_2025.09.20.25336240v1.40","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00572"},{"key":"2025092411501337000_2025.09.20.25336240v1.41","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2019.00017"},{"key":"2025092411501337000_2025.09.20.25336240v1.42","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2214"},{"key":"2025092411501337000_2025.09.20.25336240v1.43","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26308"},{"key":"2025092411501337000_2025.09.20.25336240v1.44","doi-asserted-by":"publisher","DOI":"10.1177\/2515245920928009"},{"key":"2025092411501337000_2025.09.20.25336240v1.45","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy044"},{"key":"2025092411501337000_2025.09.20.25336240v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06876-8"},{"key":"2025092411501337000_2025.09.20.25336240v1.47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"2025092411501337000_2025.09.20.25336240v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.04.028"},{"key":"2025092411501337000_2025.09.20.25336240v1.49","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00284"},{"key":"2025092411501337000_2025.09.20.25336240v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00835-z"},{"key":"2025092411501337000_2025.09.20.25336240v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01150-x"},{"key":"2025092411501337000_2025.09.20.25336240v1.52","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.7.1160"},{"key":"2025092411501337000_2025.09.20.25336240v1.53","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.3.303"},{"key":"2025092411501337000_2025.09.20.25336240v1.54","unstructured":"R Core Team. (2021). R: a language and environment for statistical computing (Version 4.1.1) [Computer software]. R Foundation for Statistical Computing."},{"key":"2025092411501337000_2025.09.20.25336240v1.55","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz4069"},{"key":"2025092411501337000_2025.09.20.25336240v1.56","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf131"},{"key":"2025092411501337000_2025.09.20.25336240v1.57","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12349"},{"key":"2025092411501337000_2025.09.20.25336240v1.58","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.20.3.310.823"},{"key":"2025092411501337000_2025.09.20.25336240v1.59","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc0655"},{"key":"2025092411501337000_2025.09.20.25336240v1.60","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012775"},{"key":"2025092411501337000_2025.09.20.25336240v1.61","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"2025092411501337000_2025.09.20.25336240v1.62","doi-asserted-by":"publisher","DOI":"10.1109\/NSSMIC.2012.6551675"},{"key":"2025092411501337000_2025.09.20.25336240v1.63","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210225"},{"key":"2025092411501337000_2025.09.20.25336240v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"2025092411501337000_2025.09.20.25336240v1.65","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.2379"},{"key":"2025092411501337000_2025.09.20.25336240v1.66","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/879716"},{"key":"2025092411501337000_2025.09.20.25336240v1.67","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"2025092411501337000_2025.09.20.25336240v1.68","unstructured":"The MathWorks Inc. (2021). MATLAB (Version R2021b) [Computer software]. The MathWorks Inc. https:\/\/www.mathworks.com"},{"key":"2025092411501337000_2025.09.20.25336240v1.69","unstructured":"Therneau, T. (2024). A package for survival analysis in R (Version 3.8-3) [Computer software]. https:\/\/CRAN.R-project.org\/package=survival"},{"key":"2025092411501337000_2025.09.20.25336240v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102733"},{"key":"2025092411501337000_2025.09.20.25336240v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0240-3"},{"key":"2025092411501337000_2025.09.20.25336240v1.72","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-009-1156-3"},{"key":"2025092411501337000_2025.09.20.25336240v1.73","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv112"},{"key":"2025092411501337000_2025.09.20.25336240v1.74","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00731-8"},{"key":"2025092411501337000_2025.09.20.25336240v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15701-2"},{"key":"2025092411501337000_2025.09.20.25336240v1.76","unstructured":"Wei, T. , & Simko, V. (2024). R package \u201ccorrplot\u201d: Visualization of a correlation matrix (Version 0.95) [Computer software]. https:\/\/github.com\/taiyun\/corrplot"},{"key":"2025092411501337000_2025.09.20.25336240v1.77","unstructured":"Wickham, H. (2016). Ggplot2: Elegant graphics for data analysis (Version 3.4.0) [Computer software]. Springer-Varlag."},{"key":"2025092411501337000_2025.09.20.25336240v1.78","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab430"},{"key":"2025092411501337000_2025.09.20.25336240v1.79","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12200"},{"key":"2025092411501337000_2025.09.20.25336240v1.80","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13318"},{"key":"2025092411501337000_2025.09.20.25336240v1.81","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14537"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.20.25336240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:46:33Z","timestamp":1768509993000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.09.20.25336240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":81,"URL":"https:\/\/doi.org\/10.1101\/2025.09.20.25336240","relation":{},"subject":[],"published":{"date-parts":[[2025,9,22]]},"subtype":"preprint"}}