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Dementia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC\u2010MTL functional connectivity (FC<jats:sub>LC\u2010MTL<\/jats:sub>) on cortical atrophy across Braak stage regions and its impact on cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We analyzed functional magnetic resonance imaging and amyloid beta (A\u03b2) positron emission tomography data from 128 cognitively normal participants, associating novelty\u2010related FC<jats:sub>LC\u2010MTL<\/jats:sub> with longitudinal atrophy and cognition with and without A\u03b2 moderation.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Cross\u2010sectionally, lower FC<jats:sub>LC\u2010MTL<\/jats:sub> was associated with atrophy in Braak stage II regions. Longitudinally, atrophy in Braak stage 2 to 4 regions related to lower baseline FC<jats:sub>LC\u2010MTL<\/jats:sub> at elevated levels of A\u03b2, but not to other regions. Atrophy in Braak stage 2\u00a0regions mediated the relation between FC<jats:sub>LC\u2010MTL<\/jats:sub> and subsequent cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>FC<jats:sub>LC\u2010MTL<\/jats:sub> is implicated in A\u03b2\u2010related cortical atrophy, suggesting that LC\u2010MTL connectivity could confer neuroprotective effects in preclinical AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Novelty\u2010related functional magnetic resonance imaging (fMRI) LC\u2010medial temporal lobe (MTL) connectivity links to longitudinal A\u03b2\u2010dependent atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This relationship extended to higher Braak stage regions with increasing A\u03b2 burden.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Longitudinal MTL atrophy mediated the LC\u2010MTL connectivity\u2013cognition relationship.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings mirror the animal data on MTL atrophy following NE signal dysfunction.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13839","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T07:35:11Z","timestamp":1714203311000},"page":"3958-3971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Atrophy links lower novelty\u2010related locus coeruleus connectivity to cognitive decline in preclinical AD"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5012-1711","authenticated-orcid":false,"given":"Christoph","family":"Schneider","sequence":"first","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prokopis C.","family":"Prokopiou","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn V.","family":"Papp","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Alzheimer Research and Treatment Department of Neurology Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Engels\u2010Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Faculty of Health Medicine and Life Sciences School for Mental Health and Neuroscience Alzheimer Centre Limburg Maastricht University, MD  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hsieh","sequence":"additional","affiliation":[{"name":"The Athinoula A. 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