White matter hyperintensity, neurofilament light chain, and cognitive decline

Abstract

Objective: We aimed to determine whether combining white matter hyperintensity (WMH) with neurofilament light chain (NfL) could provide additional information for cognition in older adults.

Methods: Utilizing data from the population-based Chicago Health and Aging Project, we studied 701 individuals with both biomarkers and cognitive data during the follow-up period. NfL was measured using an ultrasensitive immunoassay, single-molecule array technology. MRI scans of the brain were acquired using 1.5-T systems. Global cognitive function was created as a composite measure of four neuropsychological tests, standardized and averaged to z-scores. Multivariable linear mixed-effects models were used to evaluate the association of WMH and NfL with the rate of cognitive decline.

Results: Higher WMH and NfL were associated with a faster rate of cognitive decline during the follow-up; $\beta$ -coefficients (95%CIs) were -0.011 (-0.02, -0.001) and -0.010 (-0.017, -0.003), respectively. In individuals with lower concentration of NfL (i.e., bottom tertile), a higher WMH volume was associated with a faster cognitive decline ( $\beta$ : -0.030; 95%CI -0.046, -0.014). Similarly, in individuals with lower volumes of WMH (i.e., bottom tertile), a higher concentrations of NfL was associated with a faster cognitive decline ( $\beta$ : -0.023; 95%CI -0.042, -0.005). When we combined WMH with NfL, we noted a graded association with increasing volumes of WMH, particularly in people with lower NfL values.

Interpretation: While both biomarkers, WMH and NfL, were similarly associated with the annual rate of cognitive decline, our study suggests that they provide different underlying mechanisms affecting cognition.