Association of plasma neurofilament light chain (pNfL) with neuroimaging markers of neurodegeneration and cerebrovascular disease

Abstract

AbstractBackgroundCerebrospinal fluid (CSF) concentrations of neurofilament light chain (NfL) have previously been reported to be associated with severity of white matter hyperintensity (WMH) (Bjerke, M. et al. 2014; Jonsson, M. et al. 2010; Sjogren, M. et al. 2001). CSF NfL level has also been reported to be significantly increased in vascular dementia (VaD) patients compared with cognitively normal controls (NCI) (Zhao, Xin et al. 2019). However, plasma NfL (pNfL) in VaD subjects and its association with WMH or other magnetic resonance imaging (MRI) markers of cerebrovascular disease (CeVD) have yet to be investigated. The objectives of this study were to (1) examine whether pNfL levels differ between diagnostic groups (NCI, cognitive impairment no dementia [CIND], Alzheimer’s disease [AD] and VaD, and (2) assess the association between pNfL with neuroimaging markers (amyloid PET, MRI) and cognition (Mini‐Mental State Examination [MMSE] scores).MethodThis study included participants who were clinically diagnosed as NCI (n=43), CIND (n=99), VaD (n=22) or AD (n=44). Presence of significant CeVD burden (CeVD+) was defined as occurrence of cortical infarcts and/or ≥2 lacunes, and/or confluent white matter lesions on MRI. Presence of neurodegeneration (N+) was determined by medial temporal atrophy scores. Presence of elevated brain amyloid (A+) was determined by visual assessment of amyloid PET, performed with either PiB (n=178) or NAV (n=30) ligand. pNfL was measured on the Simoa‐HD 1 platform.ResultpNfL level was significantly increased in VaD and AD patients compared with NCI. Across all participants, pNfL was higher in CeVD+ or N+ groups. pNfL was associated with WMH (rho=0.304, p<0.001) and lacunes (rho=0.221, p<0.001), but not cortical infarcts. There was no difference in pNfL level between the A+ and A‐ groups. Similarly, pNfL did not correlate with SUVR measured by PiB or NAV amyloid PET tracer. Correlation between pNfL and MMSE was moderate but significant (rho=‐0.340, p<0.001). pNfL was independently associated with WMH and worse performance in MMSE.ConclusionpNfL level was increased in both VaD and AD. pNfL was associated with cognitive decline and WMH.