Differences of longitudinal plasma biomarkers between single memory domain and multidomain subject cognitive decline: Evidence from SILCODE

Background Plasma biomarkers demonstrated potential in identifying amyloid pathology in early Alzheimer's disease. Different subtypes of subjective cognitive decline (SCD) may lead to different cognitive impairment conversion risks. Objective To investigate the differences of plasma biomarkers in SCD subtypes individuals, which were unclear. Methods The 347 individuals were involved, including 93 normal controls (NC), 76 single memory domain SCD (sd-SCD), 79 multidomain SCD (md-SCD), 55 mild cognitive impairment and 44 dementia. We investigated plasma biomarkers (Aβ 42/40 , p-tau181, p-tau217, NfL, and GFAP) and neuropsychological scales in the baseline and follow-up. The Kaplan-Meier survival analysis and Cox proportional hazards model were performed to investigate the risk of cognitive decline conversion. The t-test, Mann-Whitney U and multiple linear regression analysis were employed to evaluate the rate of change and correlation between PET-SUVR and plasma biomarker change. Results In cognitively normal subjects, md-SCD exhibited lower Aβ 42/40 and higher p-tau181 and p-tau217 levels. Kaplan-Meier survival analysis revealed that md-SCD group exhibited a higher risk of cognitive decline conversion compared to NC and sd-SCD. Within SCD subgroups, those with positive GFAP status showed higher conversion risk than negative. In the Cox model, the risk of conversion in the md-SCD group was 2.77 times higher than sd-SCD. The md-SCD group demonstrated a faster rate of Aβ 42/40 decline than sd-SCD. Conclusions The study utilized plasma biomarkers to highlight the significance of staging in SCD. In cognitively normal subjects, md-SCD presents a higher risk of cognitive decline than sd-SCD, providing a valuable reference and convenient tool for early identification of individuals at risk for AD.