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To date, the specific dysfunction in the brain's hierarchical structure in AD remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We introduced the structural decoupling index (SDI), based on a multi\u2010site data set comprising functional and diffusion\u2010weighted magnetic resonance imaging data from 793 subjects, to assess their brain hierarchy.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Compared to normal controls (NCs), individuals with AD exhibited increased SDI within the posterior superior temporal sulcus, insular gyrus, precuneus, hippocampus, amygdala, postcentral gyrus, and cingulate gyrus; meanwhile, the patients with AD demonstrated decreased SDI in the frontal lobe. The SDI in those regions also showed a significant correlation with cognitive ability. Moreover, the SDI was a robust AD neuroimaging biomarker capable of accurately distinguishing diagnostic status (area under the curve [AUC]\u00a0=\u00a00.86).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our findings revealed the dysfunction of the brain's hierarchical structure in AD. Furthermore, the SDI could serve as a promising neuroimaging biomarker for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This study utilized multi\u2010center, multi\u2010modal data from East Asian populations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We found an increased spatial gradient of the structure decoupling index (SDI) from sensory\u2013motor to higher\u2010order cognitive regions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Changes in SDI are associated with energy metabolism and mitochondria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SDI can identify Alzheimer's disease (AD) and further uncover the disease mechanisms of AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14123","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:15:04Z","timestamp":1722212104000},"page":"6305-6315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Structure\u2013function coupling reveals the brain hierarchical structure dysfunction in Alzheimer's disease: A multicenter study"],"prefix":"10.1002","volume":"20","author":[{"given":"Yibao","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Artificial Intelligence in Medical Imaging School of Artificial Intelligence Beijing University of Posts and Telecommunications  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Huanhu Hospital  Tianjin 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