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, 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 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 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.