{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:30:21Z","timestamp":1792459821550,"version":"4.5.0"},"reference-count":101,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["P30 AG062677"],"award-info":[{"award-number":["P30 AG062677"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R37 AG011378"],"award-info":[{"award-number":["R37 AG011378"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 AG041851"],"award-info":[{"award-number":["R01 AG041851"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["P50 AG016574"],"award-info":[{"award-number":["P50 AG016574"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["U01 AG006786"],"award-info":[{"award-number":["U01 AG006786"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000867","name":"Robert Wood Johnson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016293","name":"Elsie and Marvin Dekelboum Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016293","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liston Family Foundation"},{"name":"Edson Family"},{"DOI":"10.13039\/100015595","name":"GHR Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015595","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation Dr. Corinne Schuler"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) emerges from multi-scale interactions between molecular pathology and disruptions in large-scale brain network dynamics. Understanding how these processes co-evolve and relate to disease stages is essential for advancing complex systems models of ageing and AD, and for developing system-informed interventions. However, progress has been limited by a lack of large-scale longitudinal data.<\/jats:p>\n                  <jats:p>To address this, we examined the longitudinal relationship between subsystems of the default mode network (DMN; posterior DMN, ventral DMN, anterior dorsal DMN) using task-free functional MRI (fMRI) and amyloid PET imaging in a large longitudinal cohort spanning the clinico-biological spectrum of AD (n = 1451; 2763 time points) using mixed-effect models. We also assessed whether patterns of DMN connectivity predicted conversion to amyloid positivity, mild cognitive impairment (MCI) and dementia using Cox proportional hazards models.<\/jats:p>\n                  <jats:p>Our findings reveal a dynamic interplay between amyloid accumulation and connectivity within and between DMN subsystems, with both hyper- and hypoconnectivity emerging across DMN subsystems in association with increasing amyloid burden. Importantly, survival models showed that DMN connectivity patterns predicted conversion to critical stages of the disease, including not only conversion to MCI and dementia, but also conversion to amyloid positivity in otherwise clinically unimpaired individuals who were amyloid negative at baseline. These associations were independent of age, APOE4 status, sex, education and in-scanner motion.<\/jats:p>\n                  <jats:p>These results support a model in which breakdowns in tightly regulated feedback loops governing DMN physiology represent a core systems-level pathophysiology of AD. Notably, this functional dyshomeostasis precedes detectable amyloidosis on imaging. Future studies should focus on the development of robust biomarkers of brain function that can be applied at the individual level, which could in turn help support the development of therapeutic approaches targeting system-level pathophysiology.<\/jats:p>","DOI":"10.1093\/brain\/awag146","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:31:47Z","timestamp":1776771107000},"source":"Crossref","is-referenced-by-count":3,"title":["Default mode network failure across the Alzheimer\u2019s disease spectrum"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6561-9870","authenticated-orcid":false,"given":"Nick","family":"Corriveau-Lecavalier","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Department of Psychiatry and Psychology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Dicks","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit , Amsterdam 1081 HZ ,","place":["The Netherlands"]},{"name":"Alzheimer Center Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit , Amsterdam 1081 HZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J","family":"Wiste","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Kamykowski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L","family":"Senjem","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-8357","authenticated-orcid":false,"given":"Christopher G","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-685X","authenticated-orcid":false,"given":"Hugo","family":"Botha","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-0691","authenticated-orcid":false,"given":"Jonathan","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Machulda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-8187","authenticated-orcid":false,"given":"Bradley F","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 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