{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:25:49Z","timestamp":1788791149892,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304245"],"award-info":[{"award-number":["82304245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Given the complexity of dementia, the inconsistent evidence on statins and dementia highlights the need for robust methods to assess heterogeneous treatment effects (HTEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We emulated a target trial using UK Biobank comparing statin initiators and non\u2010initiators aged \u226555 years. Marginal structural models were fitted to estimate 5\u2010year adjusted risk difference (aRD). We used iterative causal forest, a causal machine learning subgrouping algorithm, to identify subgroups with HTEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 18,366 participants, the overall aRD for all\u2010cause dementia was \u22121.0\u2030 (95% CI: \u22124.2\u2030 to 2.3\u2030). We identified subgroups by polygenic risk score for Alzheimer's disease (AD) excluding apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) genotype (\u201cnon\u2010\n                      <jats:italic>APOE<\/jats:italic>\n                      PRS\u201d). Participants with high non\u2010\n                      <jats:italic>APOE<\/jats:italic>\n                      PRS showed cognitive benefit (all\u2010cause dementia: aRD \u22125.9\u2030, 95% CI: \u22128.1\u2030 to 1.2\u2030; AD: aRD \u22125.0\u2030, 95% CI: \u22128.2\u2030 to \u22120.2\u2030).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Participants with high non\u2010\n                      <jats:italic>APOE<\/jats:italic>\n                      PRS may benefit from statins, suggesting genetic susceptibility beyond\n                      <jats:italic>APOE<\/jats:italic>\n                      could modify statins' cognitive effects.\n                    <\/jats:p>\n                  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