Predicting survival rate by plasma biomarkers and clinical variables in syndromes associated with frontotemporal lobar degeneration

Abstract

Introduction: Modeling the survival rate in syndromes associated with frontotemporal lobar degeneration (FTLD) is essential to assess disease trajectories.

Methods: In 262 patients with FTLD, we considered plasma neurofilament light chain (NfL), glial fibrillary acidic protein, brain-derived tau, phosphorylated tau217 and amyloid beta (Aβ42/Aβ40). The FTLD Survival Score (FTLD-SS) was calculated by the β coefficients of the variables independently associated with survival rate.

Results: Increased plasma NfL levels (p < 0.001), older age at evaluation (p = 0.002), positive family history (p = 0.04), and motor phenotypes (p < 0.001) were associated with reduced survival. The predictive validity of FTLD-SS was 0.75 (95% confidence interval, 0.59-0.91) at 1 year.

Discussion: Survival rate in FTLD is shaped by intensity of neurodegeneration (using plasma NfL as proxy) together with certain clinical variables. The FTLD-SS may serve as a simple tool for survival rate estimation and for patient stratification in clinical trials.

Highlights: Plasma neurofilament light chain and clinical variables can predict survival in frontotemporal lobar degeneration (FTLD)-associated syndromes. FTLD Survival Score (FTLD-SS), computed with survival predictors, may serve as a simple tool for patient stratification. FTLD-SS is associated with greater atrophy in frontal and putamen areas.

Keywords: biological markers; corticobasal syndrome; frontotemporal dementia; frontotemporal lobar degeneration; motor neuron disease; primary progressive aphasia; progressive supranuclear palsy; survival.