{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:37:22Z","timestamp":1788269842531,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:00:00Z","timestamp":1678579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1RO1AG069453"],"award-info":[{"award-number":["1RO1AG069453"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG072980"],"award-info":[{"award-number":["P30AG072980"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Resting\u2010state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Cognitively normal apolipoprotein E (APOE) \u03b54 carriers\/noncarriers underwent longitudinal cognitive assessment and one\u2010time MRI. The relationship of left\/right hippocampal connectivity and memory trajectory were compared between carriers\/noncarriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE \u03b54 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early\u2010stage changes in APOE \u03b54 carriers before symptoms of mild cognitive impairment are present.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Graph theory connectivity detects preclinical hippocampal changes in APOE \u03b54 carriers.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The AD disconnection hypothesis was supported in unimpaired APOE \u03b54 carriers.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hippocampal dysfunction starts asymmetrically on the left.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13023","type":"journal-article","created":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T06:35:47Z","timestamp":1678602947000},"page":"3806-3814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hippocampal connectivity and memory decline in cognitively intact APOE \u03b54 carriers"],"prefix":"10.1002","volume":"19","author":[{"given":"Leslie C.","family":"Baxter","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic Arizona  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Limback\u2010Stokin","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Arizona  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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