Serum glial fibrillary acidic protein and neurofilament light as prognostic biomarkers for clinical progression in subjective cognitive decline: The SCIENCe project

Abstract

AbstractBackgroundBlood‐based biomarkers might be easy‐to‐use tools for predicting future decline to dementia in cognitively normal individuals presenting at memory clinics (i.e. subjective cognitive decline; SCD). We previously found that glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) relate to neurodegenerative disease processes (Verberk, AAIC 2019). In this study we aimed to assess the prognostic value, by investigating the relation between baseline serum GFAP and NfL and cognitive decline in individuals with SCD.MethodWe included 303 individuals with SCD from the Amsterdam Dementia Cohort and SCIENCe project (age 61±9 years, 42% females, MMSE 28±2), who were followed annually for re‐evaluation of diagnosis and cognitive performance on a standardized neuropsychological test battery covering global cognition and the main cognitive domains (average follow‐up: 3.5 ± 2.6 years, median number visits: 3 (range 2‐12), total evaluations: 1014). Baseline serum NfL and GFAP were measured using Simoa, and Z‐transformed levels were associated with incident dementia in age and sex‐adjusted COX regression models, and with longitudinal neuropsychological test performance in age, sex and education‐adjusted linear mixed models.ResultUpon follow‐up, 27(9%) individuals developed dementia (18 Alzheimer’s, 9 non‐Alzheimer’s). High baseline GFAP was associated with increased risk of progression to dementia (HR=3.5 (95%CI: 2.2–5.7); Figure 1A), as was high baseline NfL (HR=1.8 (95%CI: 1.2–2.8); Figure 1B). When simultaneously entering both serum markers, only GFAP remained independently associated with risk of dementia (HR=3.2 (1.9–5.4); NfL: HR=1.3 (0.8–2.0)). Additionally entering plasma amyloid showed that both GFAP (HR=2.6 (1.4–4.8) and amyloid (HR=2.4 (1.2–4.5)) independently associated with risk of dementia. Investigating trajectories of cognitive decline, we found that higher baseline GFAP was associated with a steeper rate of decline on tests for global cognition, memory, attention and executive functioning (range standardized betas: ‐0.03–‐0.17, all: p<0.05FDR), but not language, whereas for NfL, none of the associations were significant after multiple testing correction (Table 1).ConclusionOur results suggest that especially GFAP is a putative prognostic blood‐based biomarker for identifying individuals with SCD at‐risk for future clinical disease progression. Serum NfL proves to be less useful as a prognostic marker in these earliest disease stages.