{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T23:29:12Z","timestamp":1783553352128,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006775","name":"GE Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the relationship between amyloid\u2010<jats:italic>\u03b2<\/jats:italic> (A<jats:italic>\u03b2<\/jats:italic>) deposition and markers of brain structure on cognitive decline in oldest\u2010old individuals with initial normal cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied cognitive functioning in four domains at baseline and change over time in fifty\u2010seven cognitively intact individuals from the EMIF\u2010AD 90+ study. Predictors were A<jats:italic>\u03b2<\/jats:italic> status determined by [<jats:sup>18<\/jats:sup>F]\u2010flutemetamol PET (normal\u00a0=\u00a0A<jats:italic>\u03b2<\/jats:italic>\u00a0\u2212\u00a0vs. abnormal\u00a0=\u00a0A<jats:italic>\u03b2<\/jats:italic>+), cortical thickness in 34 regions and hippocampal volume. Mediation analyses were performed to test whether effects of A<jats:italic>\u03b2<\/jats:italic> on cognitive decline were mediated by atrophy of specific anatomical brain areas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Subjects had a mean age of 92.7\u00a0\u00b1\u00a02.9\u00a0years, of whom 19 (33%) were A<jats:italic>\u03b2<\/jats:italic>+. Compared to A<jats:italic>\u03b2<\/jats:italic>\u2212, A<jats:italic>\u03b2<\/jats:italic>+ individuals showed steeper decline on memory (<jats:italic>\u03b2<\/jats:italic>\u00a0\u00b1\u00a0SE\u00a0=\u00a0\u22120.26\u00a0\u00b1\u00a00.09), and processing speed (<jats:italic>\u03b2<\/jats:italic>\u00a0\u00b1\u00a0SE\u00a0=\u00a0\u22120.18\u00a0\u00b1\u00a00.08) performance over 1.5\u00a0years (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Furthermore, medial and lateral temporal lobe atrophy was associated with steeper decline in memory and language across individuals. Mediation analyses revealed that part of the memory decline observed in A<jats:italic>\u03b2<\/jats:italic>+ individuals was mediated through parahippocampal atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results show that A<jats:italic>\u03b2<\/jats:italic> abnormality even in the oldest old with initially normal cognition is not part of normal aging, but is associated with a decline in cognitive functioning. Other pathologies may also contribute to decline in the oldest old as cortical thickness predicted cognitive decline similarly in individuals with and without A<jats:italic>\u03b2<\/jats:italic> pathology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51273","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:49:59Z","timestamp":1610671799000},"page":"348-358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Amyloid\u2010<i>\u03b2<\/i>, cortical thickness, and subsequent cognitive decline in cognitively normal oldest\u2010old"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6708-5374","authenticated-orcid":false,"given":"Wiesje","family":"Pelkmans","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-934X","authenticated-orcid":false,"given":"Nienke","family":"Legdeur","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8290-8543","authenticated-orcid":false,"given":"Mara","family":"ten Kate","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Radiology &amp; Nuclear Medicine Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-3706","authenticated-orcid":false,"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Nuclear Medicine Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"},{"name":"Queen Square Institute of Neurology and Centre for Medical Image Computing UCL London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-740X","authenticated-orcid":false,"given":"Maqsood M.","family":"Yaqub","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Nuclear Medicine Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7688-3087","authenticated-orcid":false,"given":"Henne","family":"Holstege","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Clinical Genetics Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1811-4383","authenticated-orcid":false,"given":"Bart N. M.","family":"van Berckel","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Nuclear Medicine Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-6408","authenticated-orcid":false,"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-6224","authenticated-orcid":false,"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Epidemiology &amp; Biostatistics Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-9727","authenticated-orcid":false,"given":"Pieter Jelle","family":"Visser","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"},{"name":"Department of Psychiatry &amp; Neuropsychology School for Mental Health and Neuroscience Maastricht University Maastricht The Netherlands"},{"name":"Department of Neurobiology, Care Sciences and Society Division of Neurogeriatrics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2612-1797","authenticated-orcid":false,"given":"Betty M.","family":"Tijms","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology I Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70139-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828ab35d"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.3391"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70194-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.6669"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009724"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000977"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.06.005"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.3029"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318266fc77"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001831"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1872-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-018-0984-z"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.046"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2015.2419072"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1997.0303"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000033967.83623.34"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.056499"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.211532"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1159"},{"key":"e_1_2_7_27_1","volume-title":"Memory scale: fourth edition technical and interpretive manual","author":"Wechsler D","year":"2009"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15324826an0302_8"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.2.126"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-013-1301-7"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.43.9.781"},{"key":"e_1_2_7_32_1","unstructured":"WechslerD.Manual for the Wechsler Adult Intelligence Scale \u2010 Revised.1981."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2466\/pms.1958.8.3.271"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1076\/clin.16.3.322.13858"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1991.00530150042015"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v059.i05"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.3098"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005291"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy150"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glz180"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828c2fc8"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.272"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.12.014"},{"key":"e_1_2_7_45_1","first-page":"160","article-title":"Amyloid burden, cortical thickness, and cognitive function in the Wisconsin Registry for Alzheimer\u2019s Prevention","volume":"1","author":"Doherty BM","year":"2015","journal-title":"Alzheimer\u2019s Dement Diagnosis, Assess Dis Monit"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.1062"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22333"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn320"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv007"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.15990"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31824b211b"},{"key":"e_1_2_7_52_1","first-page":"43","article-title":"Thinner temporal and parietal cortex is related to incident clinical progression to dementia in patients with subjective cognitive decline","volume":"5","author":"Verfaillie SCJ","year":"2016","journal-title":"Alzheimer\u2019s Dement Diagnosis Assess Dis Monit"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0299-x"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz037"},{"key":"e_1_2_7_55_1","article-title":"Understanding brain resilience in superagers: a systematic review","author":"Godoy LL","year":"2020","journal-title":"Neuroradiology"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.03.024"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22234"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3932(98)00017-7"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06616"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww017"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007133"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx320"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51273","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51273","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T10:36:10Z","timestamp":1693650970000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,9]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/acn3.51273"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51273","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,9]]},"assertion":[{"value":"2020-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}