Aging
Plasma homocysteine level and trajectories and their association with longitudinal increase in plasma neurofilament light among urban middle-aged adults May A. Beydoun* May Beydoun Nicole Noren Hooten Michael F. Georgescu Hind A. Beydoun Marie T. Fanelli-Kuczmarski Jordan Weiss Michele K. Evans Alan B. Zonderman
Background and Objectives: Plasma neurofilament light (NfL) is a non-specific marker of axonal degeneration which may be linked to elevated blood concentrations of homocysteine (Hcy). Such associations may be differential across sex and race. Therefore, we tested whether Hcy was linked to longitudinal change in plasma NfL overall and differentially across sex and race in a sample of middle-aged urban adults.
Methods: We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [n=690, Age at visit 1 (v1:2004-2009): 30-66y, 42.1% male, 55.4% African American] to evaluate relationships between NfL levels and both visit 1 Hcy (Hcyv1) and time-dependent Hcy concentrations (Hcytd). Specifically, we examined the relationship between these measures and visit 1 NfL (NfLv1) as well as annualized change in NfL (δNfL) over the study period of ~8y [2004-2009 (v1), 2009-2013 (v2) and/or 2013-2017 (v3)] using mixed effects linear regression models.
Results: Hcyv1 was positively associated with NfLv1, but not with δNfL. However, when Hcytd was considered along with time-dependent covariates on multiple-imputed data, both NfLv1 and δNfL were associated with Hcytd, 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 NfLv1 and faster increase in NfL (overall, fully adjusted, High vs. Low: γ0gbtm=+0.226±0.058, P<0.001; γ1gbtm= +0.022±0.007, P<0.010).
Discussion: Dynamic Hcy exposures (Hcytd and Hcygbtm) 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.
