{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:48:38Z","timestamp":1794242918323,"version":"4.9.0"},"reference-count":50,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p>Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer\u2019s disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40\u201489\u2009years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13\u20148.24\u2009years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (\u03b2=\u22121.43), hippocampus (\u22121.25), superior frontal gyrus (\u22121.70), middle frontal gyrus (\u22121.99), posterior cingulate (\u22122.46), and precuneus (\u22122.14), with all P-values\u2009&lt;\u20090.01. Compared with male-\u025b4 carriers, female-\u025b4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-\u025b4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-\u025b4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.<\/jats:p>","DOI":"10.1177\/0271678x211021313","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T21:17:03Z","timestamp":1623359823000},"page":"3016-3027","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["Impact of sex and\n                    <i>APOE<\/i>\n                    \u03b54 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-741X","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"first","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"The Swedish School of Sport and Health Science, GIH, Stockholm, Sweden"},{"name":"Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Oh","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, William S. 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Middleton Memorial Veterans Hospital, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B","family":"Bendlin","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"},{"name":"Geriatric Research Education and Clinical Center, William S. 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