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Cross-entropy can characterize inter-regional information flow, but its role in AD remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate cross-regional brain entropy (CRBEN) derived from resting-state fMRI in normal controls (NC), mild cognitive impairment (MCI), and AD, and to assess its potential as a biomarker of disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Resting-state fMRI data from 40 NC, 38 MCI, and 40 AD participants from ADNI 2\/3 were preprocessed using SPM12 and FSL, including motion correction (FD\u2009&lt;\u20090.5\u2005mm). Mean time series were extracted from 300 regions of the seven-network Schaefer atlas. For each subject, a 300\u2009\u00d7\u2009300 CRBEN matrix was computed and decomposed using BrainSpace to obtain functional gradients, aligned via Procrustes analysis. Group differences were tested with two-sample t-tests controlling for age, sex, and education (Bonferroni-corrected, \u03b1\u2009=\u20090.05). Machine-learning classifiers were trained using gradient and demographic features, with robustness assessed by 1000 bootstrap resamples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with NC, MCI showed reduced gradients in somatomotor, ventral-attention, and default-mode networks. AD showed further reductions versus MCI in somatomotor and default-mode networks, and versus NC in frontoparietal-control and default-mode networks (p\u2009&lt;\u20090.05, corrected). Logistic regression achieved the highest accuracy (\u223c90%). Gradient flattening was prominent in temporal and occipital cortices, indicating reduced hierarchical organization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CRBEN gradients demonstrate progressive loss of network complexity across the AD continuum and may provide sensitive biomarkers of functional disintegration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261431317","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:05:25Z","timestamp":1774857925000},"page":"301-311","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross entropy gradient analysis for Alzheimer's disease assessment"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-6028","authenticated-orcid":false,"given":"Aldo","family":"Camargo","sequence":"first","affiliation":[{"name":"University of Maryland School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1982-2875","authenticated-orcid":false,"given":"Gianpaolo Del","family":"Mauro","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-5567","authenticated-orcid":false,"given":"Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine"},{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1997.0263"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.79.061922"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2111-11.2011"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-013-9276-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02215-w"},{"key":"e_1_3_3_7_2","first-page":"43","article-title":"Alzheimer's disease puzzle: delving into pathogenesis hypotheses","volume":"15","author":"Nasb M","year":"2024","unstructured":"Nasb M, Tao W, Chen N. 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