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. 2021 Oct;17(10):1756-1762.
doi: 10.1002/alz.12324. Epub 2021 Apr 15.

Elevated plasma neurofilament light predicts a faster rate of cognitive decline over 5 years in participants with objectively-defined subtle cognitive decline and MCI

Katherine J Bangen  1   2 , Kelsey R Thomas  1   2 , Alexandra J Weigand  1   2   3 , Emily C Edmonds  1   2 , Alexandra L Clark  1   2 , Seraphina Solders  4 , Lisa Delano-Wood  1   5 , Douglas R Galasko  4 , Mark W Bondi  2   5 ; Alzheimer's Disease Neuroimaging Initiative
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Elevated plasma neurofilament light predicts a faster rate of cognitive decline over 5 years in participants with objectively-defined subtle cognitive decline and MCI

Katherine J Bangen et al. Alzheimers Dement. 2021 Oct.

Abstract

Introduction: Neurofilament light (NFL) reflects neuroaxonal damage and is implicated in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known about NFL in pre-MCI stages, such as in individuals with objectively-defined subtle cognitive decline (Obj-SCD).

Methods: Two hundred ninety-four participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent baseline blood draw and serial neuropsychological testing over 5 years of follow-up.

Results: Individuals with Obj-SCD and MCI showed elevated baseline plasma NFL relative to the cognitively normal (CN) group. Across the sample, elevated NFL predicted faster rate of cognitive and functional decline. Within the Obj-SCD and MCI groups, higher NFL levels predicted faster rate of decline in memory and preclinical AD composite score compared to the CN group.

Discussion: Findings demonstrate the utility of plasma NFL as a biomarker of early AD-related changes, and provide support for the use of Obj-SCD criteria in clinical research to better capture subtle cognitive changes.

Keywords: Alzheimer's disease; early detection; mild cognitive impairment; neurofilament light; subtle cognitive decline.

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Figures

Figure 1.
Figure 1.
Baseline NFL by cognitive group Dot-box plot showed predicted NFL from ANCOVA models adjusting for age, sex, APOE ε4 allele frequency, and CSF p-tau/Aβ positivity. lgNFL = log transformed neurofilament light; CN = cognitively normal; Obj-SCD = objectively-defined subtle cognitive difficulties; MCI = mild cognitive impairment.
Figure 2.
Figure 2.
Trajectories of cognitive performance and IADL difficulties by baseline NFL and cognitive group Model-predicted values of memory performance and Alzheimer’s preclinical composite score (mPACC) by cognitive group. Graphs illustrate predicted memory performance among those with (a) low baseline NFL and (b) high baseline NFL and Alzheimer’s preclinical composite score among those with (c) low baseline NFL and (d) high baseline NFL adjusted for age, education, sex, APOE ε4 allele frequency, and p-tau/Aβ positivity. Low and high NFL were determined by a median split of the values in the analytic sample. Shaded area represents 95% confidence intervals. NFL=neurofilament light; CN=cognitively normal; Obj-SCD=objectively-defined subtle cognitive difficulties; MCI=mild cognitive impairment.
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