Research Paper Advance Articles

Neurofilament light chain predicts risk of recurrence in cerebral amyloid angiopathy-related intracerebral hemorrhage

Xin Cheng1, *, , Ya Su1, *, , Qiong Wang2,3, , Feng Gao3, , Xiaofei Ye4, , Yiqing Wang1, , Yiwei Xia1, , Jiayu Fu1, , Yong Shen3,5, , Rustam Al-Shahi Salman6, , Qiang Dong1, ,

  • 1 Department of Neurology, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
  • 2 Department of Neurology, First Affiliated Hospital of University of Science and Technology of China, Hefei, China
  • 3 Neurodegenerative Disorder Research Centre and Institute on Aging and Brain Disorders, University of Science and Technology of China, Hefei, China
  • 4 Department of Health Statistics, Second Military Medical University, Shanghai, China
  • 5 Centre for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
  • 6 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
* Equal contribution

Received: April 6, 2020       Accepted: August 1, 2020       Published: November 18, 2020      

https://doi.org/10.18632/aging.103927
How to Cite

Copyright: © 2020 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Predicting recurrent intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) currently relies on brain images. We aimed to investigate whether blood neurodegenerative biomarkers predict disease severity and ICH recurrence in CAA. We recruited 68 first probable CAA-ICH cases from a Chinese prospective cohort, and 95 controls. We used the single-molecule array to measure acute phase blood amyloid-40, amyloid-42, total tau and neurofilament light chain (NfL). We used multivariable Cox regression models to assess the association between blood biomarkers and CAA-ICH recurrence, and used the concordance (c-) index to assess prediction models. Blood amyloid-42/40, total tau, and NfL levels changed in CAA-ICH cases than controls. During a median follow-up of 2.4 years, NfL was associated with CAA-ICH recurrence (adjusted hazard ratio 2.14, 95% CI 1.57-2.93) independent of MRI burden of small vessel disease (SVD). The performance of a model to predict CAA-ICH recurrence using MRI burden of SVD alone (c-index 0.77) increased with the addition of NfL (c-index 0.88, 95% CI 0.73-1.00, p=0.019). Further, NfL was associated with baseline ICH volume, NIHSS and 6-month mRS score. Blood NfL is associated with severity and prognosis of CAA-ICH and is a promising addition to MRI burden of SVD to predict CAA-ICH recurrence.

Abbreviations

Aβ: β-amyloid; CAA: cerebral amyloid angiopathy; CI: confidence interval; c-index: Harrell’s concordance index; CMB: cerebral microbleed; CSF: cerebrospinal fluid; CSO-PVS: periventricular space in the centrum semiovale; cSS: cerebral superficial siderosis; FLAIR: fluid attenuated inversion recovery; HR: Hazard ratio; ICH: intracerebral hemorrhage; IQR: interquartile range; MGH: Massachusetts General Hospital; mRS: modified Rankin scale; NfL: neurofilament light chain; NIHSS: NIH Stroke Scale; OR: odds ratio; SD: standard deviation; SVD: small vessel disease; SWI: susceptibility weighted imaging; WMH: white matter hyperintensity..