{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:39:15Z","timestamp":1791938355853,"version":"4.3.4"},"reference-count":73,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["23AARF\u20101026796"],"award-info":[{"award-number":["23AARF\u20101026796"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG072669"],"award-info":[{"award-number":["R01AG072669"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AG087392"],"award-info":[{"award-number":["R21AG087392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03AG070750"],"award-info":[{"award-number":["R03AG070750"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alterations in locus coeruleus\u2019 (LC) metabolic turnover are associated with Alzheimer's disease (AD)\u2010pathology and cognitive impairment. However, the evolution of these changes across disease stages and their functional relevance remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We examined associations of [\n                      <jats:sup>18<\/jats:sup>\n                      F]\u2010fluorodeoxyglucose positron emission tomography (FDG\u2010PET) \u2010derived LC metabolism with clinical diagnostic status, cerebrospinal fluid (CSF) \u2010based AD biomarkers of AD pathology, and cognitive decline in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0604).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      FDG\u2010PET\u2010derived LC metabolism was elevated in the earliest preclinical stages and lower in later disease stages. Higher LC metabolism was associated with attenuated memory decline in preclinical stages, particularly in those with low CSF A\u03b2\n                      <jats:sub>42,<\/jats:sub>\n                      but not in AD patients with cognitive impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Higher locus coeruleus [\n                      <jats:sup>18<\/jats:sup>\n                      F]\u2010FDG\u2010PET\u2010derived signal in the early preclinical stages of AD can confer cognitive resilience and may reflect increased metabolic activity, whereas later stages are characterized by lower LC FDG\u2010PET\u2010derived signal, possibly due to neurodegeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>LC FDG\u2010PET signal is lower in Alzheimer's disease (AD) patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>LC FDG\u2010PET signal is higher in the preclinical stage of AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We observed less memory decline in those with higher LC FDG\u2010PET signal.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher LC FDG\u2010PET signal conferred cognitive resilience in preclinical AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14385","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T06:22:20Z","timestamp":1732602140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Elevated locus coeruleus metabolism provides resilience against cognitive decline in preclinical Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-4254","authenticated-orcid":false,"given":"Elouise A.","family":"Koops","sequence":"first","affiliation":[{"name":"The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyita","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard J.","family":"Hanseeuw","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Alex","family":"Becker","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Van Egroo","sequence":"additional","affiliation":[{"name":"The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prokopis C.","family":"Prokopiou","sequence":"additional","affiliation":[{"name":"The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie C.","family":"Price","sequence":"additional","affiliation":[{"name":"The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Alzheimer's Clinical and Translational Research Unit, Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Center for Alzheimer Research and Treatment, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Center for Alzheimer Research and Treatment, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi I. L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Faculty of Health, Medicine and Life Sciences, Mental Health and Neuroscience Research Institute, Alzheimer Centre Limburg Maastricht University  Maastricht MD The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12387"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02477-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.06.2362"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0411-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320510"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03341.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2016.00025"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90338-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111349"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0437-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130513"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00008-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019442-199805000-00009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(94)00259-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1984.01790150033006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01901-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01269-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119658"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.01.010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj2511"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28986-2"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00062.2017"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1109\/TCI.2019.2913287"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0395"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.02.065"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.12.037"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02041-y"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.06.012"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180360"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab294"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01359-8"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1037\/neu0000835"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3102\/10769986025001060"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynirp.2020.100002"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz193"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24719"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21559"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.252"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000068478"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1071-09.2009"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1782"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.10.129"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4771-07.2008"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085885"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02248-1"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay6931"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12674"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CP02849K"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4265-05.2006"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80100"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2023.114231"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4492"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05682-3"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02380-x"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01964.x"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.4042"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91538-C"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204619119"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.03.019"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006392"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15045"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52059"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-3-15"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(87)90039-6"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.08.001"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712268115"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-019-0715-2"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:06:38Z","timestamp":1762495598000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":73,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/alz.14385"],"URL":"https:\/\/doi.org\/10.1002\/alz.14385","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,26]]},"assertion":[{"value":"2024-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14385"}}