{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:04Z","timestamp":1787008564616,"version":"build-2736575974"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":45,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R01AG066088-01"],"award-info":[{"award-number":["1R01AG066088-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1P30AG062429-01"],"award-info":[{"award-number":["1P30AG062429-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014041","name":"Alzheimer\u2019s Disease Neuroimaging Initiative","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014041","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["W81XWH-12-2-0012"],"award-info":[{"award-number":["W81XWH-12-2-0012"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The interaction between APOE \u025b4 and vascular risk factors on cognitive function is stronger in women than in men. These effects may be mediated by the amount of tau pathology in the brain. Therefore, we examined whether APOE \u025b4 and sex modify cross-sectional associations between cardiovascular risk and tau deposition in cognitively normal older adults from the Alzheimer\u2019s Disease Neuroimaging Initiative. We calculated the Framingham Heart Study cardiovascular disease risk score for 141 participants (74 women, 47 APOE \u025b4 carriers) with complete medical history data, processed tau-PET data and a Clinical Dementia Rating global score of 0.0 at the time of the tau-PET scan, implying no significant cognitive or functional impairment. We used linear regression models to examine the effects of sex, APOE \u025b4, cardiovascular risk and their interactions on tau deposition in the entorhinal cortex, inferior temporal cortex and a composite meta-region of interest of temporal lobe areas. We found a significant three-way interaction among sex, APOE \u025b4 status and cardiovascular disease risk on tau deposition in the entorhinal cortex (\u03b2\u2009=\u20090.04; 95% CI, 0.01\u20130.07; P\u2009=\u20090.008), inferior temporal cortex (\u03b2\u2009=\u20090.02; 95% CI, 0.0\u20130.05; P\u2009=\u20090.029) and meta-region (\u03b2\u2009=\u20090.02; 95% CI, 0.0\u20130.04; P\u2009=\u20090.042). After stratifying by APOE \u025b4 status to examine interactions between sex and cardiovascular disease risk on tau in APOE \u025b4 carriers and non-carriers, we found a significant two-way interaction between sex and cardiovascular disease risk on tau in the entorhinal cortex (\u03b2\u2009=\u20090.05; 95% CI, 0.02\u20130.08; P\u2009=\u20090.001), inferior temporal cortex (\u03b2\u2009=\u20090.03; 95% CI, 0.01\u20130.05; P\u2009=0.009) and meta-region (\u03b2\u2009=\u20090.02; 95% CI, 0.01\u20130.04; P\u2009=\u20090.008) only among APOE \u025b4 carriers. In analyses stratified by sex, higher cardiovascular risk scores were associated with higher levels of tau in the entorhinal cortex (\u03b2\u2009=\u20090.05; 95% CI, 0.02\u20130.08; P\u2009=\u20090.002), inferior temporal cortex (\u03b2\u2009=\u20090.02; 95% CI, 0.0\u20130.05; P\u2009=\u20090.023) and meta-region (\u03b2\u2009=\u20090.02; 95% CI, 0.01\u20130.04; P\u2009=\u20090.013) in female APOE \u025b4 carriers but not in male carriers. Our findings suggest that cognitively normal older women carrying at least one APOE \u025b4 allele, may be particularly vulnerable to the effects of cardiovascular disease risk on early tau deposition.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac035","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T23:25:44Z","timestamp":1644967544000},"source":"Crossref","is-referenced-by-count":18,"title":["Sex and\n                    <i>APOE<\/i>\n                    \u025b4 modify the effect of cardiovascular risk on tau in cognitively normal older adults"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-7335","authenticated-orcid":false,"given":"Amaryllis A.","family":"Tsiknia","sequence":"first","affiliation":[{"name":"Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Reas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Bangen","sequence":"additional","affiliation":[{"name":"Research Service, VA San Diego Healthcare System, San Diego, La Jolla, CA, USA"},{"name":"Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Sundermann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"McEvoy","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California, San Diego, La Jolla, CA, USA"},{"name":"Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Brewer","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA"},{"name":"Department of Radiology, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Edland","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Banks","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA"},{"name":"Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"2022022618502294200_fcac035-B1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13195-020-00690-7","article-title":"Associations between vascular risk factors and subsequent Alzheimer\u2019s disease in older adults","volume":"12","author":"Lee","year":"2020","journal-title":"Alzheimers Res Ther"},{"key":"2022022618502294200_fcac035-B2","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1212\/WNL.0000000000002480","article-title":"Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia aging studies","volume":"17","author":"White","year":"2016","journal-title":"Neurology"},{"key":"2022022618502294200_fcac035-B3","doi-asserted-by":"crossref","first-page":"367516","DOI":"10.1155\/2012\/367516","article-title":"Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia","volume":"2012","author":"de la Torre","year":"2012","journal-title":"Cardiovasc Psychiatry Neurol"},{"issue":"1","key":"2022022618502294200_fcac035-B4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3233\/JAD-190764","article-title":"Vascular risk factors and Alzheimer\u2019s disease: Blood-brain barrier disruption. 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