血浆神经丝轻链与非痴呆老年人小血管病负担的相关性：一项纵向研究。

Association of Plasma Neurofilament Light With Small Vessel Disease Burden in Nondemented Elderly: A Longitudinal Study.

机构信息

Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China (Y.Q., C.-C.T., L.T.).

Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, China (X.-N.S., H.-Q.L., M.C., Q.D., J.-T.Y.).

出版信息

Stroke. 2021 Mar;52(3):896-904. doi: 10.1161/STROKEAHA.120.030302. Epub 2021 Feb 1.

DOI:10.1161/STROKEAHA.120.030302

PMID:33517704

Abstract

BACKGROUND AND PURPOSE

Neurofilament light chain (NfL) is a promising predictive biomarker of active axonal injury and neuronal degeneration diseases. We aimed to evaluate if an increase in plasma NfL levels could play a monitoring role in the progression of cerebral small vessel disease (CSVD) among the nondemented elders, which are highly prevalent in elderly individuals and associated with an increased risk of stroke and dementia.

METHODS

The study included 496 nondemented participants from the Alzheimer disease neuroimaging initiative database. All participants underwent plasma NfL measurements and 3.0-Tesla magnetic resonance imaging of the brain; 387 (78.0%) underwent longitudinal measurements. The number of cerebral microbleeds, lacunar infarcts, and volumetric white matter hyperintensities, as well as Fazekas scores, were measured. Cross-sectional and longitudinal associations between CSVD burden and NfL levels were evaluated using multivariable-adjusted models.

RESULTS

Plasma NfL was higher in the moderate-severe CSVD burden group (45.2±16.0 pg/mL) than in the nonburden group (34.3±15.1 pg/mL; odds ratio [OR]=1.71 [95% CI, 1.24-2.35]) at baseline. NfL was positively associated with the presence of cerebral microbleeds (OR=1.29 [95% CI, 1.01-1.64]), lacunar infarcts (OR=1.43 [95% CI, 1.06-1.93]), and moderate-severe white matter hyperintensities (OR=1.67 [95% CI, 1.24-2.25]). Longitudinally, a higher change rate of NfL could predict more progression of CSVD burden (OR=1.38 [95% CI, 1.08-1.76]), white matter hyperintensities (OR=1.41 [95% CI, 1.10-1.79]), and lacunar infarcts (OR=1.99 [95% CI, 1.42-2.77]).

CONCLUSIONS

Plasma NfL level is a valuable noninvasive biomarker that supplements magnetic resonance imaging scans and possibly reflects the severity of CSVD burden. Furthermore, high plasma NfL levels tend to represent an increased CSVD risk, and dynamic increases in NfL levels might predict a greater progression of CSVD.

摘要

背景与目的

神经丝轻链（NfL）是一种有前途的预测生物标志物，可预测活跃的轴突损伤和神经元退行性疾病。我们旨在评估血浆 NfL 水平的升高是否可以在认知正常的老年人（在老年人中高度流行，并与中风和痴呆的风险增加有关）的脑小血管疾病（CSVD）进展中发挥监测作用。

方法

该研究纳入了来自阿尔茨海默病神经影像学倡议数据库的 496 名认知正常的参与者。所有参与者均接受了血浆 NfL 测量和 3.0-Tesla 磁共振成像检查；其中 387 名（78.0%）接受了纵向测量。测量了脑微出血、腔隙性梗死和脑白质高信号体积，以及 Fazekas 评分。使用多变量调整模型评估 CSVD 负担与 NfL 水平的横断面和纵向关联。

结果

基线时，中重度 CSVD 负担组的血浆 NfL 水平（45.2±16.0 pg/mL）高于无负担组（34.3±15.1 pg/mL；比值比[OR]=1.71[95%CI，1.24-2.35]）。NfL 与脑微出血（OR=1.29[95%CI，1.01-1.64]）、腔隙性梗死（OR=1.43[95%CI，1.06-1.93]）和中重度脑白质高信号（OR=1.67[95%CI，1.24-2.25]）的存在呈正相关。纵向来看，较高的 NfL 变化率可预测 CSVD 负担（OR=1.38[95%CI，1.08-1.76]）、脑白质高信号（OR=1.41[95%CI，1.10-1.79]）和腔隙性梗死（OR=1.99[95%CI，1.42-2.77]）的更多进展。