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However, biomarkers alone cannot indicate whether actual clinical symptoms are present or progressing. Plasma biomarkers when paired with specific cognitive deficits on brief novel Cognitive Challenge Tests (CCTs), provide excellent sensitivities to underlying AD pathology in preclinical and prodromal stage. There is a lack of data on the extent to which plasma biomarkers and CCTs independently and jointly, predict longitudinal functional decline in the earliest stages of cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate whether plasma biomarkers and CCTs independently and in combination predict baseline and longitudinal changes on the Clinical Dementia Rating scale Sum of Boxes (CDR-SOB) among older adults with cognitive impairment without dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Older adults aged 54 to 98 years diagnosed with cognitive impairment without dementia (n\u2009=\u2009159) at baseline were followed annually for a minimum of 3 visits, mean follow-up was 41.5 months (SD 11.9). CDR-SOB trajectory was estimated using latent growth curve modeling. The associations between plasma biomarkers (p-tau217, GFAP, and NfL) and CCTs with baseline levels and longitudinal change in CDR-SOB were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After adjusting for age, sex, education, Hispanic ethnicity,\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u025b4, and amyloid positivity, p-tau217 (\u03b2=0.70, SE =\u20090.23, p\u2009&lt;\u20090.01), and NfL (\u03b2=0.03, SE\u2009=\u20090.008, p\u2009&lt;\u20090.001) predicted baseline and longitudinal changes in CDR-SOB, respectively. Deficits in CCTs (\u03b2=-0.11, SE\u2009=\u20090.03, p\u2009&lt;\u20090.001) contributed independently to predicting the rate of change on CDR-SOB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrating plasma biomarkers with sensitive CCTs enhances diagnostic accuracy, monitoring, and prognosis during pre-dementia stages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261453396","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:35:32Z","timestamp":1780392932000},"page":"703-713","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining plasma biomarkers and cognitive challenge tests enhances prediction of functional trajectories of decline among older adults with cognitive impairment"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-2878","authenticated-orcid":false,"given":"D.","family":"Diane Zheng","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie E.","family":"Curiel Cid","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine"},{"name":"1Florida Alzheimer's Disease Research Center, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-4550","authenticated-orcid":false,"given":"Alexandra","family":"Ortega","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten H.","family":"Crenshaw","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of 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