{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:04:50Z","timestamp":1784837090833,"version":"3.55.0"},"reference-count":137,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":329,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"publisher","award":["#91218018"],"award-info":[{"award-number":["#91218018"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"publisher","award":["#733050812"],"award-info":[{"award-number":["#733050812"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020140","name":"Amsterdam Neuroscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020140","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer Nederland and Stichting VUmc funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Understanding the nature and onset of neurophysiological changes, and the selective vulnerability of central hub regions in the functional network, may aid in managing the growing impact of Alzheimer\u2019s disease on society. However, the precise neurophysiological alterations occurring in the pre-clinical stage of human Alzheimer\u2019s disease remain controversial. This study aims to provide increased insights on quantitative neurophysiological alterations during a true early stage of Alzheimer\u2019s disease. Using high spatial resolution source-reconstructed magnetoencephalography, we investigated regional and whole-brain neurophysiological changes in a unique cohort of 11 cognitively unimpaired individuals with pathogenic mutations in the presenilin-1 or amyloid precursor protein gene and a 1:3 matched control group (n = 33) with a median age of 49 years. We examined several quantitative magnetoencephalography measures that have been shown robust in detecting differences in sporadic Alzheimer\u2019s disease patients and are sensitive to excitation-inhibition imbalance. This includes spectral power and functional connectivity in different frequency bands. We also investigated hub vulnerability using the hub disruption index. To understand how magnetoencephalography measures change as the disease progresses through its pre-clinical stage, correlations between magnetoencephalography outcomes and various clinical variables like age were analysed. A comparison of spectral power between mutation carriers and controls revealed oscillatory slowing, characterized by widespread higher theta (4\u20138\u2005Hz) power, a lower posterior peak frequency and lower occipital alpha 2 (10\u201313\u2005Hz) power. Functional connectivity analyses presented a lower whole-brain (amplitude-based) functional connectivity in the alpha (8\u201313\u2005Hz) and beta (13\u201330\u2005Hz) bands, predominantly located in parieto-temporal hub regions. Furthermore, we found a significant hub disruption index for (phase-based) functional connectivity in the theta band, attributed to both higher functional connectivity in \u2018non-hub\u2019 regions alongside a hub disruption. Neurophysiological changes did not correlate with indicators of pre-clinical disease progression in mutation carriers after multiple comparisons correction. Our findings provide evidence that oscillatory slowing and functional connectivity differences occur before cognitive impairment in individuals with autosomal dominant mutations leading to early onset Alzheimer\u2019s disease. The nature and direction of these alterations are comparable to those observed in the clinical stages of Alzheimer\u2019s disease, suggest an early excitation-inhibition imbalance, and fit with the activity-dependent functional degeneration hypothesis. These insights may prove useful for early diagnosis and intervention in the future.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae423","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T18:16:08Z","timestamp":1732558568000},"source":"Crossref","is-referenced-by-count":6,"title":["Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer\u2019s disease: a magnetoencephalography study"],"prefix":"10.1093","volume":"6","author":[{"given":"Anne M","family":"van Nifterick","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc , 1081 HZ Amsterdam ,","place":["The Netherlands"]},{"name":"Clinical Neurophysiology and MEG Center, Neurology, Amsterdam UMC Location VUmc , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3876-1764","authenticated-orcid":false,"given":"Willem","family":"de Haan","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc , 1081 HZ Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis J","family":"Stam","sequence":"additional","affiliation":[{"name":"Clinical Neurophysiology and MEG Center, Neurology, Amsterdam UMC Location VUmc , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Clinical Neurophysiology and MEG Center, Neurology, Amsterdam UMC Location VUmc , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Brain Imaging , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Systems and Network Neurosciences , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc , 1081 HZ Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9592-3777","authenticated-orcid":false,"given":"Ronald E","family":"van Kesteren","sequence":"additional","affiliation":[{"name":"Amsterdam Neuroscience, Neurodegeneration , 1081 HV Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam , 1081 HV Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-3881","authenticated-orcid":false,"given":"Alida A","family":"Gouw","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc , 1081 HZ Amsterdam ,","place":["The Netherlands"]},{"name":"Clinical Neurophysiology and MEG Center, Neurology, Amsterdam UMC Location VUmc , 1081 HV Amsterdam 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