{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:42:02Z","timestamp":1793479322780,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early-onset Alzheimer\u2019s disease (EOAD) and late-onset Alzheimer\u2019s disease (LOAD) may differ in large-scale network organization. We compared multimodal MRI markers of diagnosis-age-defined Alzheimer\u2019s phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Alzheimer\u2019s Disease Neuroimaging Initiative participants were classified by age at first recorded mild cognitive impairment or Alzheimer\u2019s disease diagnosis: &amp;lt;65 years for EOAD and \u226565 years for LOAD. Retrospective symptom-onset information was consistent with this grouping when available. We assessed resting-state functional measures, graph-theoretical nodal metrics, structural-functional coupling (SFC), structural decoupling, and DTI-derived measures. Primary models adjusted for age and sex; sensitivity analyses examined nonlinear age, covariate overlap, clinical severity, disease stage, atrophy, biomarkers, head motion, regional coverage, and control-group composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The functional cohort included 50 EOAD, 72 LOAD, and 113 healthy controls. Global mean SFC showed only a modest group effect. LOAD showed higher regional SFC than EOAD in four frontal regions after false discovery rate correction. Graph-theoretical effects were predominantly nominal: only the overall three-group effect in Vermis 9 nodal efficiency survived within-family correction, and no EOAD-versus-LOAD nodal contrast survived. DTI-derived regional measures and structural decoupling were less subtype-discriminative. All four frontal effects remained significant after mean Power framewise displacement adjustment and overlap weighting, with bootstrap confidence intervals excluding zero. However, corrected support narrowed to one region in the nonlinear-age model and disappeared in disease- stage-, APOE \u03b5 4-, amyloid PET-, and centiloid-adjusted models; restriction to amyloid-negative controls also retained one region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the primary model, diagnosis-age-defined LOAD showed higher frontal regional SFC than EOAD. The absence of corrected EOAD-versus-LOAD graph findings, variable sensitivity-analysis support, and lack of corrected SFC\u2013clinical associations indicate a model-sensitive network phenotype rather than a definitive onset-age biomarker or clinically validated subtype marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1914358","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:26:18Z","timestamp":1788841578000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimodal network alterations in diagnosis-age-defined early- and late-onset Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"20","author":[{"given":"Zesong","family":"Yuan","sequence":"first","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Cheng","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingpeng","family":"Kuang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Luo","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e102995","DOI":"10.1371\/journal.pone.0102995","article-title":"Widespread disruption of functional brain organization in early-onset Alzheimer\u2019s disease.","volume":"9","author":"Adriaanse","year":"2014","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neuroimage.2007.07.007","article-title":"A fast diffeomorphic image registration algorithm.","volume":"38","author":"Ashburner","year":"2007","journal-title":"Neuroimage"},{"key":"B3","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation.","volume":"26","author":"Ashburner","year":"2005","journal-title":"Neuroimage"},{"key":"B4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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