NfL Levels May Predict Cognitive Decline and Neuroimaging Changes

Neural network. Computer illustration of a broken brains neural network represented by lines and dots. Some aereas are not connected, depicting dementia and Alzheimers disease.
At the AAN 2021 Virtual Annual Meeting, investigators presented their study findings comparing plasma neurofilament light (NfL) and T-tau levels in predicting cognitive decline.

The following article is part of conference coverage from the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the AAN 2021 Virtual Annual Meeting.

Plasma neurofilament light (NfL) may be effective in predicting cognitive decline and neuroimaging changes of the brain, according to study results presented during the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting, held from April 17 to 22, 2021.

Neuroimaging measures of cortical thickness, cortical atrophy, and white matter hyperintensity and integrity have been associated with elevated plasma T-tau and NfL levels. Study researchers sought to compare how T-tau protein and plasma NfL, proven blood based biomarkers for neurodegeneration, correlate to cognition and certain neuroimaging measures.

This study included a total of 995 patients enrolled in the Mayo Clinic Study on aging. Patients presented without dementia diagnosis and with concurrent plasma and T-tau protein, cognitive status, and neuroimaging data. Patients completed follow-up every 15 months for a median of 6.2 years, with researchers measuring plasma NfL and T-tau protein levels on the Simoa HD-1 Platform.

Study researchers used a linear mixed effects models adjusted for age, sex, and education to evaluate associations between baseline z-scored plasma NfL or T-tau and cognitive neuroimaging outcomes. They replicated their analyses in Alzheimer disease Neuroimaging Initiative (ADNI) with 387 patients without a dementia diagnosis and for a median of 3.0 years.

Among the 995 patients analyzed, there was a stronger association between baseline plasma NfL scores and cognitive and neuroimaging outcomes compared with T-tau scores. When both NfL and T-tau levels were elevated at baseline, study researchers identified a prominent correlation at cross-section with worse global cognition and memory and with neuroimaging measures (temporal cortex thickness, increased number of infarcts). T-tau did not contribute to the diagnostic value of NfL. Results were similar when using ADNI.

Study researchers concluded “plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes” than plasma T-tau; however, plasma T-tau may contribute “cross-sectional value to NfL in specific contexts.”

Marks J, Syrjanen J, Graff-Radford J, et al. Comparison of Neurofilament Light and Total Tau as Blood-Based Biomarkers of Neurodegeneration: Associations with Cognition and Neuroimaging Outcomes Presented at: the American Academy of Neurology 2021 Virtual Annual Meeting; April 17 to 22, 2021.