White matter retention on 18F-florbetapir positron emission tomography independently predicts cognitive decline and response to anti-amyloid therapy in Alzheimer’s disease

White matter retention on 18F-florbetapir positron emission tomography independently predicts cognitive decline and response to anti-amyloid therapy in Alzheimer’s disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article White matter retention on 18F-florbetapir positron emission tomography independently predicts cognitive decline and response to anti-amyloid therapy in Alzheimer’s disease Jin-Tai Yu, Hua-Mei Lin, Ying Zhang, Rui-Qing Ni, Min Wang, Jian-Wei Men, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7158871/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract White matter 18F-florbetapir PET signal, often dismissed as non-specific, is shown here to be a clinically relevant biomarker in Alzheimer’s disease (AD). We analyzed normal-appearing white matter (NAWM) retention in 672 participants spanning the AD continuum. NAWM retention displayed distinct temporal dynamics from cortical amyloid, increasing in preclinical stages. Higher NAWM retention independently predicted accelerated cognitive decline and clinical progression (p < 0.0001), with prognostic power comparable to established fluid biomarkers like plasma p-tau217. Furthermore, NAWM retention was responsive to lecanemab therapy. Combining NAWM and cortical amyloid measures significantly improved diagnostic accuracy for amyloid positivity to 92%, outperforming either measure alone. We conclude that NAWM 18F-florbetapir retention is an independent biomarker for AD prognostication and therapeutic monitoring, providing information beyond cortical amyloid burden. These findings support its incorporation into AD staging and clinical protocols. Health sciences/Diseases/Neurological disorders/Dementia/Alzheimer's disease Health sciences/Biomarkers/Predictive markers Alzheimer’s disease 18F-florbetapir normal-appearing white matter retention cognitive decline biomarkers Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementary.pdf White matter retention on 18F-florbetapir positron emission tomography independently predicts cognitive decline and response to anti-amyloid therapy in Alzheimer’s disease Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7158871","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":490442382,"identity":"bfb0f788-4df6-429b-aa56-b49cab529edc","order_by":0,"name":"Jin-Tai Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBACxmYQaQDE7I0PGHjAYgkEtTA2gLXwHDYgTgtIVwOYkkgmUgtzO+/xBz8KGBI33HzMJvGm5g4DP3uOAcPPHfgcxpfY2GMA1HI7mU1yzrFnDJI9bwwYe8/g08Jj2MAD1pJ/TJqH7TCDwY0cA2bGNvxaGv+AtNw8zCbN8+8wgz0xWprBttxgZpPmbQPaIkGEltkyBgzGM88kM1vO7TvMI3HmWcHBXjxaDPvPGHx884dBtu/4YcYbb74dluNvT9744Cc+LQ1g6r9jA1QAHDUHcGtgYJCH0vb4FI2CUTAKRsEIBwB7cE8+9LH/DwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-2532-383X","institution":"Huashan Hospital Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Jin-Tai","middleName":"","lastName":"Yu","suffix":""},{"id":490442383,"identity":"3ce1d4e1-adf5-48e8-be75-5c08e258b4e8","order_by":1,"name":"Hua-Mei Lin","email":"","orcid":"","institution":"Huashan Hospital, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Hua-Mei","middleName":"","lastName":"Lin","suffix":""},{"id":490442384,"identity":"6a98fda2-b794-47d3-804a-bdffc49bfdf8","order_by":2,"name":"Ying Zhang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Zhang","suffix":""},{"id":490442385,"identity":"f94a64c9-c8b0-4b6f-b9be-7e50cd008555","order_by":3,"name":"Rui-Qing Ni","email":"","orcid":"","institution":"Institute for Biomedical Engineering, University and ETH Zurich","correspondingAuthor":false,"prefix":"","firstName":"Rui-Qing","middleName":"","lastName":"Ni","suffix":""},{"id":490442386,"identity":"7d634e24-319b-4069-aa67-4a1f16277c91","order_by":4,"name":"Min Wang","email":"","orcid":"","institution":"Institute of Biomedical Engineering, School of Life Sciences, Shanghai University","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Wang","suffix":""},{"id":490442387,"identity":"13331429-28d6-4d81-b4c9-0e0dc76cc8db","order_by":5,"name":"Jian-Wei Men","email":"","orcid":"","institution":"Institute of Biomedical Engineering, School of Life Sciences, Shanghai University","correspondingAuthor":false,"prefix":"","firstName":"Jian-Wei","middleName":"","lastName":"Men","suffix":""},{"id":490442388,"identity":"87b6b468-c2f6-414c-964c-e3ca15e4c6d6","order_by":6,"name":"Jing-Jie Ge","email":"","orcid":"","institution":"Huashan Hospital, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jing-Jie","middleName":"","lastName":"Ge","suffix":""},{"id":490442389,"identity":"ef14ae5e-ff19-4154-9b64-5cb5233e0dd2","order_by":7,"name":"Jiaying Lu","email":"","orcid":"https://orcid.org/0000-0003-0927-0042","institution":"Huashan Hospital, Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jiaying","middleName":"","lastName":"Lu","suffix":""},{"id":490442390,"identity":"106d43b9-db8f-4963-ad8e-690968891ca8","order_by":8,"name":"Jing Wang","email":"","orcid":"https://orcid.org/0000-0003-2445-4966","institution":"Huashan Hospital \u0026 Human Phenome Institute, Fudan University, Shanghai, China. 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We analyzed normal-appearing white matter (NAWM) retention in 672 participants spanning the AD continuum. NAWM retention displayed distinct temporal dynamics from cortical amyloid, increasing in preclinical stages. Higher NAWM retention independently predicted accelerated cognitive decline and clinical progression (p \u003c 0.0001), with prognostic power comparable to established fluid biomarkers like plasma p-tau217. Furthermore, NAWM retention was responsive to lecanemab therapy. Combining NAWM and cortical amyloid measures significantly improved diagnostic accuracy for amyloid positivity to 92%, outperforming either measure alone. We conclude that NAWM 18F-florbetapir retention is an independent biomarker for AD prognostication and therapeutic monitoring, providing information beyond cortical amyloid burden. 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