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Genetically linking late\u2010life memory with mid\u2010life brain traits may identify early markers of AD\u2010related cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We leveraged GeNetic cOVariance Analyzer (GNOVA) to estimate genetic covariance between genome\u2010wide association studies (GWASs) of memory performance (MEM) and decline (memslopes) and 3935 UK Biobank (UKB) imaging\u2010derived phenotypes (IDPs) across diffusion, structural, and functional modalities, stratifying by cognitive status and apolipoprotein E (\n                      <jats:italic>APOE)<\/jats:italic>\n                      inclusion. Memory GWASs included 24,216 non\u2010Hispanic White older adults (mean\u00a0=\u00a074.46 years); IDP GWASs included 33,224 European\u2010ancestry mid\u2010life participants (45.1 to 81.8 years, mean\u00a0=\u00a064.28).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Diffusion and structural IDPs in medial temporal and frontal regions showed the strongest genetic covariance with memory, with additional shared genetic architecture in default mode network functional connectivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Mid\u2010life brain traits genetically linked to late\u2010life memory map to AD\u2010vulnerable regions, suggesting biologically relevant risk pathways and potential drug targets for cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71663","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:55:28Z","timestamp":1783666528000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically linked brain imaging markers of memory decline in aging and Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Yisu","family":"Yang","sequence":"first","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Sathe","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt G.","family":"Schilling","sequence":"additional","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science Vanderbilt Health Nashville Tennessee USA"},{"name":"Department of Medicine Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie S.","family":"Gaynor","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"},{"name":"Division of Geriatric Medicine, Department of Medicine Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo\u2010Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Scollard","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily H.","family":"Trittschuh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine  Seattle Washington USA"},{"name":"VA Puget Sound Health Care System, GRECC  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhabrata","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Mez","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan C.","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"},{"name":"Vanderbilt Genetics Institute Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett A.","family":"Landman","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt Health Nashville Tennessee USA"},{"name":"Vanderbilt University Institute of Imaging Science Vanderbilt Health Nashville Tennessee USA"},{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"},{"name":"Department of Electrical and Computer Engineering Vanderbilt University  Nashville Tennessee USA"},{"name":"Department of Radiology &amp; Radiological Sciences Vanderbilt Health Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul K.","family":"Crane","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cuccaro","sequence":"additional","affiliation":[{"name":"John P Hussman Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Department of Human Genetics Dr. John T. 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