INTRODUCTION: Alzheimer's disease (AD) is now diagnosed biologically. Since subjective cognitive decline (SCD) may indicate preclinical AD, assessing AD-biomarkers is crucial. We investigated cognitive and neurodegenerative trajectories in SCD over 24 months based on biomarker positivity, and evaluated the predictive value of plasma biomarkers. METHODS: The CoSCo prospective cohort included older adults with SCD. Participants were categorized into high- and low-risk groups based on plasma biomarkers (amyloid beta [Aβ] 42/40, phosphorylated tau 181 [p-tau181], and glial fibrillary acidic protein [GFAP]), and magnetic resonance imaging (MRI) findings to compare outcomes. RESULTS: High-risk SCDs (n = 23, 23%) revealed greater decline in general cognition, memory recall, frontal function, and hippocampal volumes compared to low-risk SCDs. Combined scores of plasma and MRIs yielded the best predictions compared with other biomarker categories. DISCUSSION: SCD participants with high-risk experience faster cognitive and neurodegenerative declines. A combination of plasma biomarkers and MRIs could be used for screening and prognosis. HIGHLIGHTS: This is part of a multicenter prospective cohort study in Korea. We investigated cognitive and atrophic trajectories in SCD over 24 months. High risk SCDs revealed greater cognitive decline and hippocampal atrophy. Integration of plasma and MRIs yielded better predictions than other categories. Risk stratification using plasma and MRIs can be used for screening and prognosis.