The association between neurofilament light chain and cognitive function: a UK Biobank cohort study

Blood neurofilament light chain reflects axonal injury, but its association with cognitive subdomains remains inconsistent across non-dementia populations.

Data were drawn from two waves of the UK Biobank. Participants completed tests in reaction time, fluid intelligence, prospective memory, and incorrect matches. Generalized Linear Models (GLM) and Restricted Cubic Spline (RCS) were used to examine associations between NfL levels and cognitive function, and subgroup analyses were conducted to explore these associations within specific population subgroups.

One thousand one hundred seventy-nine participants with plasma NfL measurements were evaluated at baseline. The cross-sectional results show that high NfL levels were associated with poor prospective memory in females, while no significant associations were observed in males. In participants with low education, NfL levels exhibited a non-linear relationship with fluid intelligence. The longitudinal results show that the annual change rate of reaction time increased with the annual change rate of NfL levels among participants < 60 and in females. Additionally, non-linear associations were observed between the annual change rate of NfL levels and the annual change rate of fluid intelligence in participants < 60 and in the low-education group.

This study examined the relationships between NfL levels and cognitive functions in non-dementia individuals from the UK Biobank. Overall, NfL showed linear and non-linear associations with cognitive performance, reflecting complex and variable links between neural integrity and cognition. These findings highlight that the relationships between NfL and cognition are complex and vary across populations, underscoring the need for further research to clarify the underlying mechanisms.