Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia
Weibin Ma, Jingjing Zhang, Jialei Xu, Depeng Feng, Xiaoling Wang, Fengyu Zhang
Abstract
Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mn>11.65</a:mn> <a:mo>±</a:mo> <a:mn>3.04</a:mn> </a:math> ) years and ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mn>10.53</c:mn> <c:mo>±</c:mo> <c:mn>3.87</c:mn> </c:math> ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo>=</e:mo> <e:mn>0.037</e:mn> </e:math> ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mn>8.49</g:mn> <g:mo>±</g:mo> <g:mn>2.37</g:mn> </g:math> ) pg/ml vs. ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mn>19.26</i:mn> <i:mo>±</i:mo> <i:mn>4.71</i:mn> </i:math> ) pg/ml, <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>p</k:mi> <k:mo><</k:mo> <k:mn>0.001</k:mn> </k:math> ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>r</m:mi> <m:mo>=</m:mo> <m:mn>0.238</m:mn> </m:math> , <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>p</o:mi> <o:mo>=</o:mo> <o:mn>0.041</o:mn> </o:math> ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>r</q:mi> <q:mo>=</q:mo> <q:mo>−</q:mo> <q:mn>0.213</q:mn> </q:math> , <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>p</s:mi> <s:mo>=</s:mo> <s:mn>0.040</s:mn> </s:math> ; NfL: <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>r</u:mi> <u:mo>=</u:mo> <u:mo>−</u:mo> <u:mn>0.395</u:mn> </u:math> , <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mi>p</w:mi> <w:mo>=</w:mo> <w:mn>0.027</w:mn> </w:math> ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( <y:math xmlns:y="http://www.w3.org/1998/Math/MathML" id="M13"> <y:mi>β</y:mi> <y:mo>=</y:mo> <y:mn>0.317</y:mn> </y:math> , <ab:math xmlns:ab="http://www.w3.org/1998/Math/MathML" id="M14"> <ab:mi>p</ab:mi> <ab:mo>=</ab:mo> <ab:mn>0.021</ab:mn> </ab:math> ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.