Neurofilament light and GFAP predict survival in frontotemporal dementia spectrum: A population-based study

BACKGROUND: Survival estimates for frontotemporal lobar degeneration (FTLD)-related syndromes by incorporating fluid biomarkers are essential to better assess their prognostic value and explore how they might inform long-term outcomes in FTLD. Population-based registries provide valuable data for these predictions. The aim of the present study was to assess whether NfL and GFAP levels correlate with mortality risk in a population-based registry of incident FTLD. METHODS: Incident cases with FTLD-spectrum, occurring between 2018 and 2020, were followed for up to six years. Survival and hazard analysis according to biomarkers levels were conducted. RESULTS: Median survival was 6 years from symptom onset and 3 years from diagnosis. While FTD-ALS phenotype showed significantly shorter survival, no differences were observed among bvFTD, PPAs, and CBS/PSP. Biomarkers were significantly associated with survival. Higher plasma GFAP (HR = 1.006, 95%CIs 1.001-1.012; p = 0.026) and plasma NfL (HR = 1.027, 95%CIs 1.003-1.053; p = 0.025) were associated with increased mortality risk in bvFTD, PPAs, and CBS/PSP. CONCLUSIONS: These results highlight the potential of NfL and GFAP as valuable biomarkers for assessing prognosis in FTLD and underscore the importance of incorporating biomarker analysis into clinical practice for more accurate patient management. Further studies are needed to refine prognostic models for FTLD.