Associations of Neurological Biomarkers in Serum With Gait Measures: The Cardiovascular Health Study.

Abhijay N Nadkarni, Kenneth J Mukamal, Xiaonan Zhu, David Siscovick, Jennifer S Brach, Mini Jacob, Sudha Seshadri, Temidayo Abe, Caterina Rosano, Luc Djousse, Andrea L Rosso
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Abstract

Background: Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.

Methods: We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n = 1 959, mean age = 78.0 years, 60.8% female). In a subsample (n = 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996-1997 to 1998-1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998-1999.

Results: Neurofilament light chain was significantly associated with annual gait speed decline (standardized β = -0.64 m/s, 95% CI: [-1.23, -0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses.

Conclusions: Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.

血清中的神经系统生物标志物与步态测量的关系:心血管健康研究
背景:步态障碍会导致行动能力下降,并可能与神经系统有关。本研究探讨了神经系统生物标志物与老年人步态的关系:我们对心血管健康研究(Cardiovascular Health Study)中的参与者进行了研究,该研究是一项基于人群的美国老年人队列研究,研究人员对 1996-97 年收集的样本进行了血清生物标志物评估,包括神经丝蛋白轻链(NfL)、胶质纤维酸性蛋白(GFAP)、泛素羧基末端水解酶 L1(UCH-L1)和总 tau(n=1959,平均年龄=78.0 岁,60.8% 为女性)。在一个子样本(n=380)中,探讨了与定量步态测量的横截面关联。该子样本在垫子上对步态速度、步长、双支撑时间、步幅、步长变异性和步幅变异性进行了评估。从 1996-97 年到 1998-99 年,每年还在 15 英尺的人行道上测量步速,以进行纵向分析。线性回归模型评估了生物标志物与步态测量的横向联系,而混合效应模型则评估了从基线到1998-99年的纵向步态速度变化:在对人口统计学和健康因素进行调整后,NfL与每年步速的下降有明显的相关性(标准化β=-0.64 m/s,95% CI:[-1.23, -0.06])。在步态垫评估的表型中,NfL与步态速度也有横截面相关性(β = 0.001 m/s [0.0003,0.002]),但与其他步态指标无关。在纵向或横截面分析中,其余生物标志物均与步态无明显关系:结论:NfL水平越高,每年步速下降的幅度越大。步速下降可能与轴索变性有关。应探讨NfL的临床实用性。
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