{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:10Z","timestamp":1787018110777,"version":"build-2736575974"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Our previous preclinical study demonstrated that\n                      <jats:italic>APOE4<\/jats:italic>\n                      \u2010targeted replacement mice exhibit more severe cerebral hypoperfusion and cognitive impairment than\n                      <jats:italic>APOE3<\/jats:italic>\n                      \u2010targeted replacement mice with carotid artery stenosis due to neurovascular dysfunction. Therefore, we clinically investigate whether\n                      <jats:italic>APOE4<\/jats:italic>\n                      contributes to cerebral hemodynamic and cognitive impairment in subjects with asymptomatic carotid artery stenosis or occlusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A cross\u2010sectional observational study was conducted between January 2017 and March 2022. In a primary analysis, 91 subjects (114 affected cerebral hemispheres) with asymptomatic carotid artery stenosis or occlusion who underwent neuropsychological examinations and\n                      <jats:sup>15<\/jats:sup>\n                      O\u2010gas positron emission tomography were included to examine associations of\n                      <jats:italic>APOE4<\/jats:italic>\n                      with cognitive impairment and cerebral hemodynamic impairment. A sensitivity analysis was performed with 161 subjects (201 affected cerebral hemispheres) who underwent\n                      <jats:sup>15<\/jats:sup>\n                      O\u2010gas positron emission tomography scan. In the primary analysis, 20 (22.0%) subjects were\n                      <jats:italic>APOE4<\/jats:italic>\n                      carriers.\n                      <jats:italic>APOE4<\/jats:italic>\n                      was an independent risk factor of lower cerebral blood flow in the anterior circulation territory (\u03b2=\u22120.058 [95% CI, \u22120.098 to \u22120.018],\n                      <jats:italic>P<\/jats:italic>\n                      =0.005) and short\u2010term memory impairment in Alzheimer's Disease Assessment Scale\u2010Cognitive Subscale 13 (\u03b2=1.16 [95% CI, 0.009\u20132.30],\n                      <jats:italic>P<\/jats:italic>\n                      =0.048) in a multivariable linear regression analysis. In the sensitivity analysis, 31 (19.3%) subjects carried\n                      <jats:italic>APOE4<\/jats:italic>\n                      , which was an independent risk factor of lower cerebral blood flow (\u03b2=\u22120.048 [95% CI, \u22120.079 to \u22120.012],\n                      <jats:italic>P<\/jats:italic>\n                      =0.003) in the anterior circulation territory.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:italic>APOE4<\/jats:italic>\n                      may confer an increased risk of decreased cerebral blood flow accompanied by memory impairment in asymptomatic carotid artery stenosis or occlusion consistent with our experimental study.\n                      <jats:italic>APOE<\/jats:italic>\n                      genotyping in such subjects may be useful for early detection of disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.039210","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:33:56Z","timestamp":1741847636000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Cerebral Hemodynamic Impairment and Cognitive Dysfunction in\n                    <i>APOE4<\/i>\n                    Carriers With Asymptomatic Carotid Artery Stenosis\/Occlusion"],"prefix":"10.1161","author":[{"given":"Yoshinori","family":"Kakino","sequence":"first","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-4433","authenticated-orcid":false,"given":"Yorito","family":"Hattori","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]},{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-376X","authenticated-orcid":false,"given":"Soshiro","family":"Ogata","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-574X","authenticated-orcid":false,"given":"Yuriko","family":"Nakaoku","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-0949","authenticated-orcid":false,"given":"Kunihiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7914-3068","authenticated-orcid":false,"given":"Hidehiro","family":"Iida","sequence":"additional","affiliation":[{"name":"University of Turku and Turku General Hospital","place":["Turku, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-4048","authenticated-orcid":false,"given":"Masafumi","family":"Ihara","sequence":"additional","affiliation":[{"name":"National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000090791"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13139-019-00633-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00359-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318295d71a"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31824365d3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.04.038"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-019-1127-y"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.047160"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1547-z"},{"key":"e_1_3_2_11_2","unstructured":"Taconic Biosciences . 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