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While cardiovascular risk tends to affect cognition from midlife, it remains unclear whether heritable risk predicts cardiovascular health in young adulthood and midlife, and whether young-adult cardiovascular health predicts midlife cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We sought to examine how heritable dementia risk relates to cardiovascular health and how these cardiovascular risk factors in young adulthood predict midlife brain volumes and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used data from the CARDIA study, which followed 5115 individuals aged 18\u201330 at baseline over 30 years. Analyses focused on 2808 participants (Mean age\u2009=\u200960,\n                      <jats:italic toggle=\"yes\">SD<\/jats:italic>\n                      \u2009=\u20093.58) who attended the 30-year visit. We examined associations between\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      and FH with baseline and 30-year follow-up measures of cardiovascular risk factors (LDL-C, HDL-C, glucose, blood pressure, body mass index (BMI), smoking), cognition, and brain volumes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      carriers with FH had higher LDL-C and lower HDL-C levels as early as young adulthood, persisting into midlife. BMI and smoking were the only cardiovascular risk factors from young adulthood that predicted midlife cognition. There was no association between young adult cardiovascular risk factors and midlife brain volumes, but those with heritable dementia risk had larger brain volumes in regions vulnerable to midlife atrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">APOE4<\/jats:italic>\n                      carriership was associated with an unfavorable lipid profile that started in early adulthood and persisted to later life. Early cardiovascular risk was also associated with midlife cognition, which is earlier than studies typically focusing on later-life cognition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251401482","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T17:56:25Z","timestamp":1767722185000},"page":"757-767","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Relationships between heritable dementia risk factors, cardiovascular risk factors in young adulthood, and midlife neuropsychological outcomes"],"prefix":"10.1177","volume":"109","author":[{"given":"Ivan","family":"Koychev","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-0902","authenticated-orcid":false,"given":"Nemanja","family":"Vaci","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Moonen","sequence":"additional","affiliation":[{"name":"Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6079-9323","authenticated-orcid":false,"given":"Graham","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Experimental Psychology, University of Oxford, Oxford, UK"},{"name":"Oxford Institute of Clinical Psychology Training and Research, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Howgego","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9388-0443","authenticated-orcid":false,"given":"Christoph","family":"Jindra","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, UK"},{"name":"Institute for Educational Quality Improvement (IQB), Humboldt Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gallacher","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenore J.","family":"Launer","sequence":"additional","affiliation":[{"name":"Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30367-6"},{"key":"e_1_3_3_3_2","article-title":"Insulin resistance, age and depression's impact on cognition in middle-aged adults from the PREVENT cohort","volume":"26","author":"Sarah DB","year":"2023","unstructured":"Sarah DB, Michael Ben Y, Graham R, et al. 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