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. 2019 Jul 16;93(3):e252-e260.
doi: 10.1212/WNL.0000000000007767. Epub 2019 Jun 10.

Plasma and CSF neurofilament light: Relation to longitudinal neuroimaging and cognitive measures

Michelle M Mielke  1 , Jeremy A Syrjanen  2 , Kaj Blennow  2 , Henrik Zetterberg  2 , Prashanthi Vemuri  2 , Ingmar Skoog  2 , Mary M Machulda  2 , Walter K Kremers  2 , David S Knopman  2 , Clifford Jack Jr  2 , Ronald C Petersen  2 , Silke Kern  2
Affiliations

Plasma and CSF neurofilament light: Relation to longitudinal neuroimaging and cognitive measures

Michelle M Mielke et al. Neurology. .

Abstract

Objective: We aimed to (1) assess and compare baseline plasma and CSF neurofilament light (NfL) for cross-sectional and longitudinal associations with neuroimaging or cognition and (2) determine whether change in plasma NfL corresponded with change in these outcomes.

Methods: Seventy-nine participants without dementia, median age 76 years, had plasma and CSF NfL, neuropsychological testing, and neuroimaging (MRI, amyloid PET, FDG-PET) at the same study visit, and a repeat visit (15 or 30 months later) with both plasma NfL and neuroimaging. Plasma NfL was measured on the Simoa-HD1 Platform and CSF NfL with an in-house ELISA. Linear mixed effects models were used to examine the associations between baseline plasma or CSF NfL and cognitive and neuroimaging outcomes adjusting for age, sex, and education. The relationship between change in plasma NfL and change in the outcomes was assessed using linear regression.

Results: There were no cross-sectional associations between CSF or plasma NfL and any neuroimaging or cognitive measure. Longitudinally, higher baseline plasma NfL was associated with worsening in all neuroimaging measures, except amyloid PET, and global cognition. Higher baseline CSF NfL was associated with worsening in cortical thickness and diffusion MRI. The beta estimates for CSF NfL were similar to those for plasma NfL. Change in plasma NfL was associated with change in global cognition, attention, and amyloid PET.

Conclusion: Elevated baseline plasma NfL is a prognostic marker of cognitive decline and neuroimaging measures of neurodegeneration, and has similar effect sizes to baseline CSF NfL. Change in plasma NfL also tracked with short-term cognitive change.

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Figures

Figure
Figure. Longitudinal associations between baseline z log-transformed plasma or CSF neurofilament light (NfL) and neuroimaging and cognitive measures
(A) Everyone. (B) The 64 cognitively unimpaired (CU) participants at baseline. (C) The 62 participants with a 30-month follow-up. CI = confidence interval; DTI = diffusion tensor imaging; FDG = [18F]-fluorodeoxyglucose.
See this image and copyright information in PMC

References

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