Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment

Amish Gaur; Damien Gallagher; Nathan Herrmann; Jinghan Jenny Chen; Susan Marzolini; Paul Oh; Yutaka Amemiya; Arun Seth; Alex Kiss; Krista L Lanctôt

doi:10.1177/08919887241254469

Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment

J Geriatr Psychiatry Neurol. 2024 May 17:8919887241254469. doi: 10.1177/08919887241254469. Online ahead of print.

Authors

Amish Gaur^{1

2}, Damien Gallagher^{1

3}, Nathan Herrmann^{1

3}, Jinghan Jenny Chen^{1

2}, Susan Marzolini⁴, Paul Oh⁴, Yutaka Amemiya⁵, Arun Seth^{5

6}, Alex Kiss¹, Krista L Lanctôt^{1

2

3

4}

Affiliations

¹ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
² Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
³ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁴ KITE Research Institute, Toronto Rehabilitation Institute, Toronto, ON, Canada.
⁵ Genomics Core Facility, Sunnybrook Research Institute, Toronto, ON, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

PMID: 38757180
DOI: 10.1177/08919887241254469

Abstract

Background: Neurofilament Light Chain (NfL) is a biomarker of axonal injury elevated in mild cognitive impairment (MCI) and Alzheimer's disease dementia. Blood NfL also inversely correlates with cognitive performance in those conditions. However, few studies have assessed NfL as a biomarker of global cognition in individuals demonstrating mild cognitive deficits who are at risk for vascular-related cognitive decline.

Objective: To assess the relationship between blood NfL and global cognition in individuals with possible vascular MCI (vMCI) throughout cardiac rehabilitation (CR). Additionally, NfL levels were compared to age/sex-matched cognitively unimpaired (CU) controls.

Method: Participants with coronary artery disease (vMCI or CU) were recruited at entry to a 24-week CR program. Global cognition was measured using the Montreal Cognitive Assessment (MoCA) and plasma NfL level (pg/ml) was quantified using a highly sensitive enzyme-linked immunosorbent assay.

Results: Higher plasma NfL was correlated with worse MoCA scores at baseline (β = -.352, P = .029) in 43 individuals with vMCI after adjusting for age, sex, and education. An increase in NfL was associated with worse global cognition (b[SE] = -4.81[2.06], P = .023) over time, however baseline NfL did not predict a decline in global cognition. NfL levels did not differ between the vMCI (n = 39) and CU (n = 39) groups (F(1, 76) = 1.37, P = .245).

Conclusion: Plasma NfL correlates with global cognition at baseline in individuals with vMCI, and is associated with decline in global cognition during CR. Our findings increase understanding of NfL and neurobiological mechanisms associated with cognitive decline in vMCI.

Keywords: Alzheimer’s disease; cardiac rehabilitation; global cognition; mild cognitive impairment; neurofilament light chain; vascular cognitive impairment.