Factors influencing serum neurofilament light chain levels in normal aging

Objective: Serum neurofilament light (sNfL) is a promising marker for neuro-axonal damage and it is now well known that its levels also increase with higher age. However, the effect of other determinants besides age is still poorly investigated. We therefore aimed to identify factors influencing the sNfL concentration by analysing a large set of demographical, life-style and clinical variables in a normal aging cohort. Methods: sNfL was quantified by single molecule array (Simoa) assay in 327 neurologically inconspicuous individuals (median age 67.8±10.7 years, 192 female) who participated in the Austrian Stroke Prevention Family Study (ASPS-Fam). Random forest regression analysis was used to rank the association of included variables with sNfL in the entire cohort and in age-stratified subgroups. Linear regression then served to identify factors independently influencing sNfL concentration. Results: Age (β=0.513, p<0.001) was by far the most important factor influencing sNfL, which was mainly driven by individuals ≥60 years. In age stratified sub-groups, body mass index (BMI) (β=-0.298, p<0.001) independently predicted sNfL in individuals aged 38-60 years. In individuals ≥60 years, age (β=0.394, p<0.001), renal function (β=0.376, p<0.001), blood volume (β=-0.198, p=0.008) and high density lipoprotein (HDL) (β=0.149, p=0.013) were associated with sNfL levels. Conclusions: Age is the most important factor influencing sNfL concentrations, getting increasingly relevant in elderly people. BMI further influences sNfL levels, especially at younger age, whereas renal function gets increasingly relevant in the elderly.