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A Support Vector Machine was trained on 25 plasma biomarkers spanning neurodegeneration, inflammation, and vascular health, along with demographic factors (age, sex, ethnicity, karyotype, apolipoprotein E [\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54]). Batch\u2010effect correction and feature selection were applied, resulting in 13 key markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The refined model achieved 92.4% sensitivity, 59.9% specificity, and an area under the curve (AUC) of 77.9%, accurately identifying individuals at risk of cognitive decline up to 16 months before clinical progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This multi\u2010domain, blood\u2010based machine learning approach demonstrates that plasma biomarkers are valuable non\u2010invasive tools for early detection and risk stratification of cognitive decline in DS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71659","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:17:32Z","timestamp":1784085452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood biomarkers predict conversion from cognitively stable to mild cognitive impairment or Alzheimer's disease in Down syndrome at 16\u2010month follow\u2010up in ABC\u2010DS"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-1808","authenticated-orcid":false,"given":"Fan","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute for Translational Research University of North Texas Health Science Center  Fort Worth Texas USA"},{"name":"Department of Family Medicine University of North Texas Health Science Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Petersen","sequence":"additional","affiliation":[{"name":"Institute for Translational Research University of North Texas Health Science Center  Fort Worth Texas USA"},{"name":"Department of Family Medicine University of North Texas Health Science Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mapstone","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hall","sequence":"additional","affiliation":[{"name":"Institute for Translational Research University of North Texas Health Science Center  Fort Worth Texas USA"},{"name":"Department of Family Medicine University of North Texas Health Science Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Handen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Christian","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Psychiatry University of Wisconsin Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, Department of Neurology University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herminia Diana","family":"Rosas","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Radiology, Massachusetts General Hospital Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H","family":"Lee","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University Irving Medical Center  New York New York USA"},{"name":"Department of Epidemiology, Mailman School of Public Health Columbia University  New York New York USA"},{"name":"Department of Neurology, Neurological Institute Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J","family":"Krinsky\u2010McHale","sequence":"additional","affiliation":[{"name":"Department of Psychology New York State Institute for Basic Research in Developmental Disabilities  Staten Island New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Harp","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Hom","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Human Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira T.","family":"Lott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigan","family":"Hartley","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Studies University of Wisconsin\u2013Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge  Cambridge Cambridgeshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M.","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Ptomey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pittsburgh Pennsylvania  Pittsburgh USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sid E. 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