Plasma homocysteine level and trajectories in association with longitudinal increase in plasma neurofilament light among urban adults.

We tested whether homocysteine (Hcy) was linked to longitudinal change in plasma neurofilament light chain (NfL) overall and differentially across sex and race in a sample of middle-aged urban adults. We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [n = 690, Age at visit 1 (v:2004-2009): 30-66y, 42.1% male, 55.4% African American] to evaluate relationships between NfL levels and both visit 1 Hcy (Hcy) and time-dependent Hcy concentrations (Hcy). Specifically, we examined the relationship between these measures and visit 1 NfL (NfL) as well as annualized change in NfL (δNfL) over the study period of ~ 8y [2004-2009 (v), 2009-2013 (v) and/or 2013-2017 (v)] using mixed effects linear regression models. Hcy was positively associated with NfL, but not with δNfL. However, when Hcy was considered along with time-dependent covariates on multiple-imputed data, both NfL and δNfL were associated with Hcy, with some significant sex difference in the longitudinal association, whereby this relationship was stronger among males. The Hcy exposure obtained from group-based trajectory models, indicated that individuals belonging to the "High increasing" group were consistently associated with both higher NfL and faster increase in NfL (overall, fully adjusted, High vs. Low: γ =  + 0.226 ± 0.058, P < 0.001; γ =  + 0.022 ± 0.007, P < 0.010). Dynamic Hcy exposures (Hcy and Hcy) were associated with faster rate of increase in NfL over time, reflecting potentially faster rate of axonal degeneration. Further studies are needed in comparable populations to replicate our findings.