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The study utilized a sliding\u2010window approach to assess whole\u2010brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid\u2010related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant group difference concerning were observed in relation to <jats:italic>APOE<\/jats:italic>\u2010\u03b54 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state\u20101 characterized by frequent but weak connections, and state\u2010II characterized by less frequent but strong connections. Pre\u2010AD subjects exhibited a preference for spending more time in state\u2010I, whereas AD patients tended remain in state\u2010II for longer periods. Group difference in dFNC was primarily found between AD and non\u2010AD participants within each state. The dFNC of state\u2010I yielded strong power to distinguish AD from other groups compared with state\u2010II. <jats:italic>APOE<\/jats:italic>\u2010\u03b54<jats:sup>+<\/jats:sup>, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state\u2010I, whereas differential connections of state\u2010II mediated the relationships between <jats:italic>APOE<\/jats:italic>\u2010\u03b54 genotype and CSF biomarkers, and cognitive indicators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The dysfunction of dFNC temporal\u2013spatial patterns and increased cognition in individuals with <jats:italic>APOE<\/jats:italic>\u2010\u03b54, high polygenic score, and higher serum lipid levels shed light on the lipid\u2010related mechanisms of dynamic network reorganization in AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70029","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T12:15:52Z","timestamp":1726834552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Feifei","family":"Zang","sequence":"first","affiliation":[{"name":"Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine Southeast University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine Southeast University  Nanjing Jiangsu 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