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In addition, we developed a novel region set enrichment analysis (RSEA) to detect brain functional changes based on metabolic variations. Results were aligned with transcriptomic signatures and clinical cognitive assessments (CCAs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Our findings highlight sexual dimorphic changes across the disease spectrum, which suggest brain network reorganization occurs as compensatory mechanisms due to pathological disruptions. RSEA indicated functional changes in motor, memory, language, and cognitive functions related to disease progression, and these changes were supported by transcriptomic signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Together, metabolic covariance analysis, regional connectomics, and RSEA allow for AD progression tracking and functional alteration identification based on metabolic readouts, consistent with CCA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71218","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:02:52Z","timestamp":1777374172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiscale metabolic covariance networks uncover stage\u2010specific biomarker signatures across the Alzheimer's disease continuum"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-2294","authenticated-orcid":false,"given":"Juan Antonio K.","family":"Chong Chie","sequence":"first","affiliation":[{"name":"Stark Neuroscience Research Institute Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Persohn","sequence":"additional","affiliation":[{"name":"Stark Neuroscience Research Institute Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi S.","family":"Pandey","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia R.","family":"Simcox","sequence":"additional","affiliation":[{"name":"Wood College of Osteopathic Medicine Marian University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Carter","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Salama","sequence":"additional","affiliation":[{"name":"School of Electrical and Computer Engineering Purdue University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-332X","authenticated-orcid":false,"given":"Paul R.","family":"Territo","sequence":"additional","affiliation":[{"name":"Stark Neuroscience Research Institute Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging 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