Associations of plasma neurofilament light protein levels with cognitive functions and brain structure parameters

Abstract Background Neurofilament light (NfL) protein level is considered a non‐specific marker of neurodegeneration. NfL levels have been associated with established, non‐blood based neurodegenerative markers, including cognitive performance and reduced brain volume. However, most studies were small (N<300), compared in patients (MCI, Alzheimer’s disease) those healthy controls. We investigated to what extent are MRI measures volume microstructure, large non‐demented population‐based sample. Method The analyses on 4,578 participants (30‐95 years) the Rhineland Study, community‐based cohort study Bonn, Germany. Plasma measured SIMOA platform. assessed tests for memory, processing speed, executive function crystallized intelligence an eye movement (EM) test battery. 3,206 persons underwent structural diffusion weighted MR imaging. Imaging outcomes included volumetric (total brain, grey matter, white hippocampus); tensor (fractional anisotropy; mean, radial, axial diffusivity); neurite orientation dispersion density imaging (NODDI) measures. used multivariable regression models assess relation between adjustment possible confounders. Result Across all participants, we found only negligibly associations performance, age‐stratified revealed that age 40‐49 from 60 onwards higher lower index (ODI). In 70‐ 79‐year‐olds, additionally prosaccade accuracy, radial diffusivity, extracellular intracellular fraction index. 80+‐year‐olds, negatively hippocampal matter positively fractional anisotropy diffusivity. Conclusion Higher smaller NODDI older subjects. younger (up 70 years), ODI. This suggests sensitive subtle changes especially old age.