{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:08:49Z","timestamp":1791911329394,"version":"4.3.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30-AG062715"],"award-info":[{"award-number":["P30-AG062715"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL118154"],"award-info":[{"award-number":["HL118154"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL007936"],"award-info":[{"award-number":["HL007936"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["17-499398"],"award-info":[{"award-number":["17-499398"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Cerebral blood flow at rest declines with age. However, age-related changes in functional measures of cerebrovascular health including cerebrovascular reactivity and neurovascular coupling are not well understood. Additionally, the effect of apolipoprotein E (\n                    <jats:italic>APOE<\/jats:italic>\n                    ) \u03b54, a strong genetic risk factor for Alzheimer\u2019s disease, on cerebral blood flow and cerebrovascular function remains unclear.\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 positive (\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54+; n = 37, age = 63\u00b14y) and\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 negative (\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54-; n = 50, age = 63\u00b14y) cognitively unimpaired adults participated in this study. Macrovascular cerebral blood flow and microvascular cerebral perfusion were measured using 4D flow MRI and pseudo-continuous arterial spin labeling MRI, respectively. Cerebrovascular reactivity and neurovascular coupling were assessed by measuring middle cerebral artery blood velocity in response to hypercapnia and the\n                    <jats:italic>n<\/jats:italic>\n                    -back test, respectively. Neurovascular coupling was lower in\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54+ compared with\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54- adults (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05), despite higher cerebral blood flow and cerebrovascular reactivity to hypercapnia. Alterations in neurovascular coupling may occur early, prior to changes in cognition, in aging\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 carriers.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0314744","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T13:28:10Z","timestamp":1733232490000},"page":"e0314744","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lower neurovascular coupling response despite higher cerebral blood flow at rest in apolipoprotein \u025b4 positive adults"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-936X","authenticated-orcid":true,"given":"Andrew G.","family":"Pearson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-3978","authenticated-orcid":true,"given":"Kathleen B.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam T.","family":"Corkery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Loggie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna J.","family":"Howery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo A.","family":"Rivera-Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Wieben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6317-4153","authenticated-orcid":true,"given":"Jill N.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"pone.0314744.ref001","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"EH Corder","year":"1993","journal-title":"Science"},{"key":"pone.0314744.ref002","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.apsb.2021.10.002","article-title":"Apolipoprotein E and Alzheimer\u2019s disease.","volume":"12","author":"BR Troutwine","year":"2022","journal-title":"Acta Pharmaceutica Sinica"},{"key":"pone.0314744.ref003","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.","volume":"9","author":"C-C Liu","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"pone.0314744.ref004","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1161\/STR.0b013e3182299496","article-title":"Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association\/american stroke association","volume":"42","author":"PB Gorelick","year":"2011","journal-title":"Stroke"},{"key":"pone.0314744.ref005","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10571-015-0261-z","article-title":"The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer\u2019s Disease","volume":"36","author":"CC Hays","year":"2016","journal-title":"Cell Mol Neurobiol"},{"issue":"Suppl 4","key":"pone.0314744.ref006","doi-asserted-by":"crossref","first-page":"S411","DOI":"10.3233\/JAD-141467","article-title":"Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer\u2019s disease","volume":"42","author":"CE Wierenga","year":"2014","journal-title":"J Alzheimers Dis"},{"issue":"Pt 1","key":"pone.0314744.ref007","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/brain\/113.1.27","article-title":"Cerebral blood flow, blood volume and oxygen utilization. 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