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We hypothesize that WMH not only directly contributes to cognitive decline but also moderates the relationship among AD pathology, treatment, and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A total of 1169 participants with 240\u2010week follow\u2010up in the Anti\u2010Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were analyzed. Linear regression models examined WMH's contribution to cognitive decline, its interaction with A\u03b2 on p\u2010Tau217 level, and its interaction with anti\u2010amyloid treatment on cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Increase in WMH volume independently contributed to cognitive decline (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0028). Baseline WMH significantly moderated the relationship between A\u03b2 change and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010Tau217 change (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0035). Specifically, A\u03b2 accumulation correlated with p\u2010Tau217 increase only in participants with low baseline WMH. WMH growth was associated with cognitive decline only in the treatment group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>WMH modulates the interplay of pathologies, emphasizing the need for comprehensive treatment approaches targeting multiple pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>White matter hyperintensity (WMH) independently contributed to cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>WMH modulated the longitudinal relationship between A\u03b2 and p\u2010Tau217.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>WMH interacted with anti\u2010amyloid treatment on longitudinal cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70990","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:32:02Z","timestamp":1765344722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["White matter hyperintensity modulates the amyloid\u2010tau\u2010cognition association and anti\u2010amyloid treatment efficacy in asymptomatic older adults"],"prefix":"10.1002","volume":"21","author":[{"given":"Zixuan","family":"Lin","sequence":"first","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education Department of Biomedical Engineering College of Biomedical Engineering &amp; Instrument Science Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Hong","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education Department of Biomedical Engineering College of Biomedical Engineering &amp; Instrument Science Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhe","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education Department of Biomedical Engineering College of Biomedical Engineering &amp; Instrument Science Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Statistics School of Mathematical Sciences Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010Lei","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Science China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education Department of Biomedical Engineering College of Biomedical Engineering &amp; Instrument Science Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of 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