The following is a summary of “Clinical Value of Longitudinal Serum Neurofilament Light Chain in Prodromal Genetic Frontotemporal Dementia,” published in the July 2023 issue of Neurology by Giannini et al.
Neurofilament light chain (NfL) increases in serum reveal frontotemporal dementia (FTD) variants, but the timeline remains unclear for carriers. Researchers performed a cohort study to assess the predictive and early diagnostic potential of longitudinal serum NfL for prodromal conversion in genetic FTD.
They analyzed a cohort of genetic FTD pathogenic variant carriers to examine diagnostic accuracy and conversion risk linked to cross-sectional and longitudinal NfL levels. Investigators compared periods relative to prodromal conversion (>3, 3-1.5, 1.5-0 years before; 0-1.5 years after) with non-converting participants. Additionally, they modeled longitudinal NfL and MRI volume trajectories to determine their timeline.
The results showed 82 participants, 21 converted (5 C9orf72, 10 GRN, 5 MAPT, 1 TARDBP), and 61 did not (20 C9orf72, 30 GRN, 11 MAPT). Those who converted showed consistently higher NfL levels before prodromal conversion (median values 14.0-18.2 pg/mL; betas=0.4-0.7, SE=0.1, p<0.046) compared to non-converters (6.5 pg/mL) and had a further increase 0-1.5 years after conversion (28.4 pg/mL; beta=1.0, SE=0.1, p<0.001). Annualized longitudinal NfL change was significantly higher in converters 0-1.5 years after conversion (beta=1.2, SE=0.3, p=0.001).
The diagnostic accuracy of NfL for prodromal conversion was good-to-excellent before conversion (AUC range: 0.72-0.92), improved 0-1.5 years after conversion (0.94-0.97), and outperformed annualized longitudinal change (0.76-0.84). NfL increase in converters preceded frontotemporal MRI volume change, and this pattern varied based on genetics and clinical phenotypes. Higher NfL levels corresponded to increased conversion risk (hazard ratio: cross-sectional=6.7 [95%CI 3.3-13.7]; longitudinal=13.0 [95%CI 4.0-42.8]; p<0.001), but the time to conversion-free follow-up varied significantly among participants.
Investigators concluded MRI shows an NfL increase in individuals converting to prodromal FTD, but its timing is limited and varies depending on variant-carrying genes and clinical phenotypes.