Serum neurofilament light chain level as a predictor of cognitive stage transition

Abstract

Background: Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants.

Methods: This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high.

Results: The Kaplan-Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor.

Conclusion: The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.

Keywords: Alzheimer’s disease; Amyloid pathology; Cognitive stage; Cortical thickness; Neurofilament light chain.

Fig. 1

Cognitive stage transition. Kaplan–Meier curves for cognitive stage transition according to the serum NFL tertile in participants with mild cognitive impairment (A), cognitively unimpaired (B), and total participants (C)

Fig. 2

The correlation between the cortical thickness and serum NFL levels. The correlation between the cortical thickness of specific brain regions and serum NFL levels is represented using different colors. The positive and negative correlation coefficients are shown in red and blue, respectively. Statistical significance was analyzed using Spearman’s bivariate correlation (*p value < 0.05, **p value < 0.01). PreCG, precentral gyrus; SFGdor, superior frontal gyrus (dorsal); ORBsup superior orbital gyrus; MFG, middle frontal gyrus; ORBmid, middle orbital gyrus; IFGoperc, inferior frontal gyrus pars opercularis; IFGtriang, inferior frontal gyrus pars triangularis; ORBinf, inferior orbital gyrus; ROL, rolandic operculum; SMA, supplementary motor area; OLF, olfactory cortex, SFGmed, superior frontal gyrus (medial); ORBsupmed, superior frontal gyrus (medial orbital); REC, gyrus rectus; INS, insula; ACG, anterior cingulate gyrus; DCG, dorsal cingulate gyrus; PCG, posterior cingulate gyrus; PHG, parahippocampal gyrus; CAL, calcarine fissure and surrounding cortex; CUN, cuneus; LING, lingual gyrus; SOG, superior occipital gyrus; MOG, middle occipital gyrus; IOG, inferior occipital gyrus; FFG, fusiform gyrus; PoCG, postcentral gyrus; SPG, superior parietal gyrus; IPL, inferior parietal lobule; SMG, supra marginal gyrus; ANG, angular gyrus; PCUN, precuneus; PCL, paracentral lobule; HES, Heschl’s gyrus; STG, superior temporal gyrus; TPOsup, superior temporal pole; MTG, middle temporal gyrus; TPOmid, middle temporal pole; ITG, inferior temporal gyrus