Harvard Medical School, Boston, MA, USA/Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA/Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA/Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
Mult Scler. 2023 Feb;29(2):206-211. doi: 10.1177/13524585221137697. Epub 2022 Nov 30.
Cognitive decline is inadequately captured by the standard neurological examination. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are biomarkers of neuronal damage and astrocytic reactivity that may offer an accessible measure of the multiple sclerosis (MS) pathology linked to cognitive decline.
To investigate the association of sNfL and sGFAP with cognitive decline in MS patients at high risk for progressive pathology.
We included 94 MS patients with sustained Expanded Disability Status Score (EDSS) ⩾ 3, available serum samples and cognitive assessment performed by symbol digit modalities test (SDMT) over a median of 3.1 years. The visit for sGFAP/sNfL quantification was at confirmed EDSS ⩾ 3. Linear regression analysis on log-transformed sGFAP/sNfL assessed the association with current and future SDMT. Analyses were adjusted for age, sex, EDSS, treatment group, and recent relapse.
sNfL was significantly associated with concurrent SDMT (adjusted change in mean SDMT = -4.5; 95% confidence interval (CI): -8.7, -0.2; = 0.039) and predicted decline in SDMT (adjusted change in slope: -1.14; 95% CI: -1.83, -0.44; = 0.001), particularly in active patients. sGFAP was not associated with concurrent or future SDMT.
Higher levels of sNfL were associated with cognitive impairment and predicted cognitive decline in MS patients at high risk for having an underlying progressive pathology.
标准的神经检查不能充分评估认知能力下降。血清神经丝轻链（sNfL）和胶质纤维酸性蛋白（sGFAP）是神经元损伤和星形胶质细胞反应的生物标志物，它们可能提供一种可测量的多发性硬化症（MS）与认知能力下降相关的病理学方法。
研究在有进展性病理学风险的 MS 患者中，sNfL 和 sGFAP 与认知能力下降的相关性。
我们纳入了 94 名 MS 患者，这些患者的扩展残疾状况评分（EDSS）持续 ⩾3，有血清样本，并且在中位数为 3.1 年的时间内通过符号数字模式测试（SDMT）进行认知评估。进行 sGFAP/sNfL 定量检测的就诊时间是确诊的 EDSS ⩾3。对 log 转换后的 sGFAP/sNfL 进行线性回归分析，以评估其与当前和未来 SDMT 的相关性。分析调整了年龄、性别、EDSS、治疗组和最近的复发。
sNfL 与当前的 SDMT 显著相关（调整后的平均 SDMT 变化值为-4.5；95%置信区间（CI）：-8.7，-0.2； = 0.039），并且预测了 SDMT 的下降（调整后的斜率变化值为-1.14；95% CI：-1.83，-0.44； = 0.001），特别是在活跃的患者中。sGFAP 与当前或未来的 SDMT 无关。
较高的 sNfL 水平与 MS 患者的认知障碍相关，并预测了有潜在进展性病理学的 MS 患者的认知能力下降。
