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Additionally, apolipoprotein E (APOE) \u03b54 carriers may be at an increased risk for greater WMH volumes and hippocampal atrophy in aging. The present study sought to investigate whether regional WMH volume mediates the relationship between age and hippocampal volume and if this association is moderated by APOE \u03b54 status in a group of 190 cognitively healthy adults (APOE \u03b54 status [carrier\/non\u2010carrier] = 59\/131), ages 50\u201389. Analyses revealed that temporal lobe WMH volume significantly mediated the relationship between age and average bilateral hippocampal volume, and this effect was moderated by APOE \u03b54 status (\u22120.020 (SE = 0.009), 95% CI, [\u22120.039, \u22120.003]). APOE \u03b54 carriers, but not non\u2010carriers, showed negative indirect effects of age on hippocampal volume through temporal lobe WMH volume (APOE \u03b54 carriers: \u22120.016 (SE = 0.007), 95% CI, [\u22120.030, \u22120.003]; APOE \u03b54 non\u2010carriers: .005 (SE = 0.006), 95% CI, [\u22120.006, 0.017]). These findings remained significant after additionally adjusting for sex, years of education, hypertension status and duration, cholesterol status, diabetes status, Body Mass Index, history of smoking, and the Wechsler Adult Intelligence Scale\u2010IV Full Scale IQ. There were no significant moderated mediation effects for frontal, parietal, and occipital lobe WMH volumes, with or without covariates. Our findings indicate that in cognitively healthy older adults, elevated WMH volume regionally localized to the temporal lobes in APOE \u03b54 carriers is associated with reduced hippocampal volume, suggesting greater vulnerability to brain aging and the risk for Alzheimer's disease.<\/jats:p>","DOI":"10.1002\/hipo.23308","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T04:15:30Z","timestamp":1613621730000},"page":"469-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Influence of regional white matter hyperintensity volume and apolipoprotein E \u03b54 status on hippocampal volume in healthy older adults"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-2138","authenticated-orcid":false,"given":"Emily J.","family":"Van Etten","sequence":"first","affiliation":[{"name":"Department of Psychology University of Arizona  Tucson Arizona USA"},{"name":"Evelyn F. 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