Beydoun May A, Hooten Nicole Noren, Georgescu Michael F, Beydoun Hind A, Fanelli-Kuczmarski Marie T, Weiss Jordan, Evans Michele K, Zonderman Alan B
Laboratory of Epidemiology and Population Sciences, NIA Biomedical Research Center/NIH/IRP, Baltimore, MD, 21224, USA.
VA National Center On Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC, USA.
Geroscience. 2025 Feb 19. doi: 10.1007/s11357-025-01567-z.
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.
我们在一个中年城市成年人样本中测试了同型半胱氨酸（Hcy）是否与血浆神经丝轻链（NfL）的纵向变化相关，以及在性别和种族之间是否存在差异。我们使用了来自“全生命周期邻里多样性健康老龄化”（HANDLS）研究的数据[n = 690，首次访视时（v：2004 - 2009年）的年龄：30 - 66岁，42.1%为男性，55.4%为非裔美国人]来评估NfL水平与首次访视时的Hcy（Hcy）以及随时间变化的Hcy浓度（Hcy）之间的关系。具体而言，我们使用混合效应线性回归模型，研究了这些指标与首次访视时的NfL（NfL）以及在约8年的研究期间[2004 - 2009年（v）、2009 - 2013年（v）和/或2013 - 2017年（v）]NfL的年化变化（δNfL）之间的关系。Hcy与NfL呈正相关，但与δNfL无关。然而，当在多重填补数据上同时考虑Hcy和随时间变化的协变量时，NfL和δNfL均与Hcy相关，在纵向关联中存在一些显著的性别差异，即这种关系在男性中更强。从基于群体的轨迹模型获得的Hcy暴露表明，属于“高增长”组的个体始终与更高的NfL以及NfL更快的增长相关（总体而言，完全调整后，高组与低组相比：γ = +0.226 ± 0.058，P < 0.001；γ = +0.022 ± 0.007，P < 0.010）。动态Hcy暴露（Hcy和Hcy）与NfL随时间更快的增长速率相关，反映出潜在的轴突变性速率更快。需要在可比人群中进行进一步研究以重复我们的发现。
