{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:36Z","timestamp":1783003896515,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp; Dem Diag Ass &amp; Dis Mo"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Both elevated cortisol and hippocampal volume have been linked to an increased risk for the development of Alzheimer's disease (AD). This longitudinal study assessed the effects of plasma cortisol on hippocampal atrophy and clinical progression rates in patients with mild cognitive impairment (MCI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with amnestic MCI (<jats:italic>n<\/jats:italic>\u00a0=\u00a0304) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on availability of baseline plasma cortisol and hippocampal volume measures, assessed at baseline and during follow\u2010ups. We investigated associations between plasma cortisol, hippocampal volume, and risk of clinical progression to AD over a study period of up to 100 months (mean follow\u2010up time 36.8 months) using linear mixed models, Cox proportional hazards models, and Kaplan\u2010Meier estimators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma cortisol predicted greater hippocampal atrophy, such that participants with higher cortisol showed faster decline in hippocampal volume over time (interaction: \u03b2\u00a0=\u00a0\u20100.15, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.004). Small hippocampal volume predicted a higher risk of clinical progression to AD (haard ratio [HR]\u00a0=\u00a02.15; confidence in terval [CI], 1.64\u20132.80; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). A similar effect was not found for cortisol (HR\u00a0=\u00a01.206; CI, 0.82\u20131.37; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.670) and there was no statistical evidence for an interaction between hippocampal volume and cortisol on clinical progression (HR\u00a0=\u00a00.81; CI, 0.57\u20130.17; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.260).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest that higher cortisol predicts higher hippocampal atrophy, which in turn is a risk factor for progression to AD. Regulation of the hypothalamic\u2010pituitary\u2010adrenal axis through stress\u2010reducing lifestyle interventions might be a protective factor against hippocampal degeneration at the prodromal stage of AD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.12463","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T02:21:15Z","timestamp":1691979675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment"],"prefix":"10.1002","volume":"15","author":[{"given":"Silke","family":"White","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden Saxony Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Mauer","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics and Biometry Faculty of Medicine Dresden University of Technology Dresden Saxony Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Klimecki","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden Saxony Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"Huijbers","sequence":"additional","affiliation":[{"name":"Biogen Digital Health Biogen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranka","family":"Wirth","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden Saxony Germany"}],"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":[[2023,8,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro\u20102014\u20100035"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2797\u201006.2006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0730\u201011.2011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011\u20100145"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.04.017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00043"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100404.1990.tb00994.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000048637"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.07.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1154112"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.10.031"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.7.1397"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.08.003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2008.12.026"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.08.008"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1176\/AJP.2006.163.12.2164"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsc.2016.08.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.3135"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055531"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20103956(82)90033\u20104"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20103956(75)90026\u20106"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412\u2010a"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1155"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.141.11.1356"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.5_Suppl_6.10S"},{"key":"e_1_2_9_27_1","unstructured":"ADNI. 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