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These associations are often observed only in the later stages of decline. This study examined if hippocampal grading, a method measuring local morphological similarity of the hippocampus to cognitively normal controls (NCs) and AD participants, is associated with cognition in NCs, subjective cognitive decline (SCD), early (eMCI), late (lMCI), and AD. A total of 1620 Alzheimer's Disease Neuroimaging Initiative participants were examined (495 NC, 262 eMCI, 545 lMCI, and 318\u00a0AD) because they had baseline MRIs and Alzheimer's disease Assessment Scale (ADAS\u201013) and Clinical Dementia Rating\u2014Sum of Boxes (CDR\u2010SB) scores. In a sub\u2010analysis, NCs with episodic memory scores (as measured by Rey Auditory Verbal Learning Test, RAVLT) were divided into those with subjective cognitive decline (SCD+; 103) and those without (SCD\u2212; 390). Linear regressions evaluated the influence of hippocampal grading on cognition in preclinical and prodromal AD. Lower global cognition, as measured by increased ADAS\u201013, was associated with hippocampal grading: NC (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), eMCI (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05), lMCI (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05), and AD (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.01). Lower global cognition as measured increased CDR\u2010SB was associated with hippocampal grading in lMCI (<jats:italic>p\u2009&lt;<\/jats:italic>\u00a0.05) and AD <jats:italic>(p<\/jats:italic>\u2009&lt;\u2009.001). Lower RAVLT performance was associated with hippocampal grading in SCD\u2212 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05) and SCD+ (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). These findings suggest that hippocampal grading is associated with global cognition in NC, eMCI, lMCI, and AD. Early changes in episodic memory during pre\u2010clinical AD are associated with changes in hippocampal grading. Hippocampal grading may be sensitive to progressive changes early in the disease course.<\/jats:p>","DOI":"10.1002\/hbm.26269","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T12:00:49Z","timestamp":1679313649000},"page":"3147-3157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The use of hippocampal grading as a biomarker for preclinical and prodromal Alzheimer's disease"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-5770","authenticated-orcid":false,"given":"Cassandra","family":"Morrison","sequence":"first","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute, McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Dadar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McGill University  Montreal Quebec Canada"},{"name":"McGill Univeristy Douglas Mental Health University Institute  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Shafiee","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute, McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Louis","family":"Collins","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute, McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"For Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"What is Alzheimer's disease","author":"Alzheimer's Association","year":"2021"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2007.06.004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2006.01.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.04.030"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/gbz120"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.10.080"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2012.10.002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22926"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2007.906087"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12091"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.03.025"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102353"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1010"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2014.02.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.07.033"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.12.002"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.4.993"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018.NIA-AA"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa287"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1109\/ICCUBEA.2018.8697386"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.102079"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2008.04.014"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.12.011"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","unstructured":"Morrison C. 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