{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T08:19:46Z","timestamp":1793866786272,"version":"4.6.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>\nAbstract\n<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The role of cerebral blood flow (CBF) in the early stages of Alzheimer\u2019s disease is complex and largely unknown. We investigated cross-sectional and longitudinal associations between CBF, amyloid burden, and cognition, in cognitively normal individuals with subjective cognitive decline (SCD).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We included 187 cognitively normal individuals with SCD from the SCIENCe project (65\u2009\u00b1\u20098\u00a0years, 39% F, MMSE 29\u2009\u00b1\u20091). Each underwent a dynamic (0\u201370\u00a0min) [<jats:sup>18<\/jats:sup>F]florbetapir PET and T1-weighted MRI scan, enabling calculation of mean binding potential (BP<jats:sub>ND<\/jats:sub>; specific amyloid binding) and <jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> (measure of relative (r)CBF). Eighty-three individuals underwent a second [<jats:sup>18<\/jats:sup>F]florbetapir PET (2.6\u2009\u00b1\u20090.7\u00a0years). Participants annually underwent neuropsychological assessment (follow-up time 3.8\u2009\u00b1\u20093.1\u00a0years; number of observations <jats:italic>n<\/jats:italic>\u2009=\u2009774).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A low baseline <jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> was associated with steeper decline on tests addressing memory, attention, and global cognition (range betas 0.01 to 0.27, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). High BP<jats:sub>ND<\/jats:sub> was associated with steeper decline on tests covering all domains (range betas\u2009\u2212\u20090.004 to\u2009\u2212\u20090.70, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). When both predictors were simultaneously added to the model, associations remained essentially unchanged. Additionally, we found longitudinal associations between <jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> and BP<jats:sub>ND<\/jats:sub>. High baseline BP<jats:sub>ND<\/jats:sub> predicted decline over time in <jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> (all regions, range betas<jats:sub>BP\u00d7time<\/jats:sub>\u2009\u2212\u20090.09 to\u2009\u2212\u20090.14, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Vice versa, low baseline <jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> predicted increase in BP<jats:sub>ND<\/jats:sub> in frontal, temporal, and composite ROIs over time (range betas<jats:sub><jats:italic>R<\/jats:italic>1\u00d7time<\/jats:sub>\u2009\u2212\u20090.03 to\u2009\u2212\u20090.08, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results suggest that amyloid accumulation and decrease in rCBF are two parallel disease processes without a fixed order, both providing unique predictive information for cognitive decline and each process enhancing the other longitudinally.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-022-05958-8","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T03:25:13Z","timestamp":1662607513000},"page":"410-422","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cerebral blood flow, amyloid burden, and cognition in cognitively normal individuals"],"prefix":"10.1007","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-7224","authenticated-orcid":false,"given":"Jarith L.","family":"Ebenau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander C. 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A.","family":"van Leeuwenstijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara ten","family":"Kate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert D.","family":"Windhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels D.","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Boellaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart N. 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In the past two years, he has received consultancy\/speaker fees (paid to the institution) from Probiodrug Biogen, EIP Pharma, Merck AG.Niels Prins is consultant to Boehringer Ingelheim, Aribio, and Amylyx. He is co-PI of a study with Fuji Film Toyama Chemical. He serves on the DSMB of Abbvie\u2019s M15-566 trial. NP has received a speaker fee from Biogen. Payments were made to his company. He is CEO and co-owner of the Brain Research Centre, The Netherlands.Ronald Boellaard reports no disclosures relevant to the manuscript.Bert Windhorst reports no disclosures relevant to the manuscript.Wiesje van der Flier Research programs have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health\u2009~\u2009Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. WF is recipient of a grant for the Heart-Brain Connection crossroads (HBCx) consortium of the Dutch CardioVascular Alliance (DCVA). This work was supported by the Dutch Heart Foundation [#2018\u201328]. WF holds the Pasman chair. WF has performed contract research for Biogen MA Inc and Boehringer Ingelheim. WF has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai and WebMD Neurology (Medscape). WF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF was associate editor at <i>Alzheimer\u2019s Research & Therapy<\/i> (2020\u20132021); She is associate editor of <i>Brain<\/i> (2021\u2013). All funding is paid to her institution.Bart van Berckel has received research support from EU-FP7, CTMM, ZonMw, NWO, and Alzheimer Nederland. BvB has performed contract research for Rodin, IONIS, AVID, Eli Lilly, UCB, DIAN-TUI, and Janssen. BvB was a speaker at a symposium organized by Springer Healthcare. BvB has a consultancy agreement with IXICO for the reading of PET scans. BvB is a trainer for GE. BvB only receives financial compensation from Amsterdam UMC.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}