Contributors to Serum NfL Levels in People without Neurologic Disease.

Contributors to Serum NfL Levels in People without Neurologic Disease.
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DOI:
10.1002/ana.26446
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发表时间:
2022-10
影响因子:
11.2
通讯作者:
Calabresi, Peter A.
Calabresi, Peter A.
中科院分区:
医学1区
文献类型:
--
作者:
Fitzgerald, Kathryn C.;Sotirchos, Elias S.;Smith, Matthew D.;Lord, Hannah-Noelle;DuVal, Anna;Mowry, Ellen M.;Calabresi, Peter A.

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评估人口统计学、生活方式因素和合并症对无神经系统疾病人群血清神经丝轻链(sNfL)水平的影响,并建立人口统计学特异性的sNfL参考范围。国家健康和营养检查调查(NHANES)是美国人口的代表性样本,系统地收集了人口统计、生活方式、常规实验室检查和整体健康状况的详细信息。从储存的血清样本中,我们使用一种新型的高通量免疫分析法(Siemens Healthineers)测量sNfL水平。我们评估了52个人口统计学、生活方式、合并症、人体测量学或实验室特征在解释sNfL水平变异性方面的预测能力。使用交叉验证的R2 (R2cv)评估预测性能,并使用正向选择获得一组最佳sNfL水平预测因子。利用位置、规模和形状的广义加性模型,推导出调整后的参考范围。我们纳入了1706名无神经系统疾病的NHANES参与者(平均年龄:43.6±14.8岁;50.6%为男性,35%为非白人)。在单变量模型中,年龄解释了sNfL的最大变异性(R2cv=26.8%)。sNfL的多变量预测模型包含3个协变量(按选择顺序):年龄、肌酐和糖化血红蛋白(HbA1c)(标准化β -年龄:0.46,95% CI: 0.43, 0.50;肌酐:0.18,95% CI: 0.13, 0.22; HbA1c: 0.09, 95% CI: 0.06, 0.11)。调整后的百分位曲线纳入确定的预测因子。我们提供了一个交互式的R Shiny应用程序来翻译我们的发现,并允许其他研究人员使用衍生的百分位曲线。结果将有助于指导解释sNfL水平,因为它们与神经系统状况有关。
To assess the effects of demographics, lifestyle factors, and comorbidities on serum neurofilament light chain (sNfL) levels in people without neurologic disease and establish demographic-specific reference ranges of sNfL. The National Health and Nutrition Examination Survey (NHANES) is a representative sample of the US population in which detailed information on demographic, lifestyle, routine laboratory tests and overall health status are systematically collected. From stored serum samples, we measured sNfL levels using a novel high-throughput immunoassay (Siemens Healthineers). We evaluated the predictive capacity of 52 demographic, lifestyle, comorbidity, anthropometric, or laboratory characteristics in explaining variability in sNfL levels. Predictive performance was assessed using cross-validated R2 (R2cv) and forward selection was used to obtain a set of best predictors of sNfL levels. Adjusted reference ranges were derived incorporating characteristics using generalized additive models for location, scale and shape. We included 1706 NHANES participants (average age: 43.6±14.8y; 50.6% male, 35% non-white) without neurological disorders. In univariate models, age explained the most variability in sNfL (R2cv=26.8%). Multivariable prediction models for sNfL contained 3 covariates (in order of their selection): age, creatinine, and glycosylated hemoglobin (HbA1c) (standardized β – age: 0.46, 95% CI: 0.43, 0.50; creatinine: 0.18, 95% CI: 0.13, 0.22; HbA1c: 0.09, 95% CI: 0.06, 0.11). Adjusted centile curves were derived incorporating identified predictors. We provide an interactive R Shiny application to translate our findings and allow other investigators to use the derived centile curves. Results will help to guide interpretation of sNfL levels as they relate to neurologic conditions.
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