Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI. •Plasma and cerebrospinal fluid neurofilament light (NFL) were moderately correlated.•Cerebrospinal fluid NFL was related to language and memory functions.•Plasma NFL exhibited widespread cognitive associations.•Plasma NFL associations were particularly robust in mild cognitive impairment.