{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:06:13Z","timestamp":1779793573303,"version":"3.53.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Stroke and\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 are established risk factors of dementia. However, it remains unclear whether stroke interacts with\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      genotypes to influence dementia occurrence. This study aims to investigate the associations of stroke and its interaction by\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      genotypes with incident risk of dementia, with a specific focus on peripheral clues for biological mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This prospective cohort study included 336\u2009903 participants (mean age: 56.3\u2009years, stroke history: 1.3%,\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54: 28.5%) from the UK Biobank, with a median follow\u2010up of 13\u2009years. Cumulative incidence curves were constructed using Fine\u2013Gray death competing risks analysis. The additive and multiplicative interaction of stroke (including ischemic and hemorrhagic stroke) with\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      genotypes on incident risk of all\u2010cause dementia (ACD) and Alzheimer disease were examined. Blood proteomics combined with bioinformatics analyses were used to explore the peripheral clues for biological mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Either ischemic or hemorrhagic stroke was significantly associated with elevated risk of ACD and Alzheimer disease (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). A significant multiplicative interaction was observed between stroke and\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). The association of stroke with increased risk of dementia was stronger in\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers than carriers, for both ACD (hazard ratio [HR], 1.93 for carriers and 3.36 for non\u2010carriers,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) and AD (HR, 1.14 for carriers and 2.67 for non\u2010carriers,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). Inflammation\u2010related pathways could be mechanisms underpinning the association of stroke with ACD risk. We identified 191 functionally interconnected (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;1.0\u00d710\n                      <jats:sup>\u221216<\/jats:sup>\n                      ) proteins associated with both stroke and ACD only in\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers. CD4\u2010related and TGF\u2010beta (transforming growth factor beta) signaling pathway could mediate the strengthened relationship in\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers.\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                      Stroke interacts with\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 to influence dementia, with the association being more pronounced in\n                      <jats:italic toggle=\"no\">APOE<\/jats:italic>\n                      \u03b54 non\u2010carriers. Future studies are needed to verify the underpinning mechanisms to guide precise prevention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043446","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:46:13Z","timestamp":1765968373000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["<i>APOE<\/i>\n                    Genotype Modulates the Relationship of Stroke With Dementia Risk: Associations and Peripheral Clues for Biological Mechanisms"],"prefix":"10.1161","volume":"15","author":[{"given":"Chong\u2010Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"Qingdao University","place":["Qingdao, 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