Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

Marco Egle; Laurence Loubiere; Aleksandra Maceski; Jens Kuhle; Nils Peters; Hugh S Markus

doi:10.1136/jnnp-2020-325681

Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

J Neurol Neurosurg Psychiatry. 2021 Feb 8;92(6):582-589. doi: 10.1136/jnnp-2020-325681. Online ahead of print.

Authors

Marco Egle¹, Laurence Loubiere², Aleksandra Maceski³, Jens Kuhle³, Nils Peters^{4

5}, Hugh S Markus²

Affiliations

¹ Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK me417@medschl.cam.ac.uk.
² Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
³ Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
⁴ Stroke Center, Klinik Hirslanden, Zürich, Switzerland.
⁵ Stroke Center and Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.

Abstract

Objectives: Serum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk.

Methods: Patients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years.

Results: NfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β=-0.335, SE=0.094, p=0.001) and risk of converting to dementia (HR=1.676 (95% CI 1.183 to 2.373), p=0.004). In contrast to imaging, there was no change in NfL values over the follow-up period.

Conclusions: Baseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD.