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Total WMH load was determined from T2\u2010FLAIR magnetic resonance scans using the TrUE\u2010Net deep learning tool for white matter segmentation. In separate models, we used mediation analysis to assess whether pulse pressure or MAP mediates the relationship between age and total white matter hyperintensity load, controlling for cardiovascular confounds. We also assessed whether white matter hyperintensity load mediated the relationship between age and cognitive scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pulse pressure, but not mean arterial pressure, significantly mediated the relationship between age and white matter hyperintensity load. White matter hyperintensity load partially mediated the relationship between age and Montreal Cognitive Assessment score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results indicate that pulse pressure, but not mean arterial pressure, is mechanistically associated with age\u2010related accumulation of white matter hyperintensities, independent of other cardiovascular risk factors. White matter hyperintensity load was a mediator of cognitive scores across the adult lifespan. Effective management of pulse pressure may be especially important for maintenance of brain health and cognition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.70086","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T11:55:18Z","timestamp":1748174118000},"page":"1520-1527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pulse Pressure, White Matter Hyperintensities, and Cognition: Mediating Effects Across the Adult Lifespan"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-9905","authenticated-orcid":false,"given":"Jade","family":"Hannan","sequence":"first","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Newman\u2010Norlund","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-7899","authenticated-orcid":false,"given":"Natalie","family":"Busby","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"},{"name":"Linguistics Program, College of Arts and Sciences University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Newman\u2010Norlund","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Arts and Sciences University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Rorden","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Arts and Sciences University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Fridriksson","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Department of Neurology University of South Carolina School of Medicine  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.11.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000053"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41440\u2010021\u201000704\u20103"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24320"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103323"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103480"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103077"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.241465"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2014.884087"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2023.08.007"},{"key":"e_1_2_9_12_1","volume-title":"StatPearls","author":"Homan T. 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