Correlation Of Serum Neurofilament Light Chain Protein Levels Combined With Inflammatory Markers With Cognitive Dysfunction In Cerebral Small Vessel Disease

ObjectiveTo investigate the correlation between serum neurofilament light chain(NFL)levels and white matter hyperintensities(WMH)in cerebral small vessel disease(CSVD),and whether this correlation could become a new blood marker or complement imaging features to assess cognitive decline in CSVD.To investigate whether there was a correlation between NFL levels and traditional markers of inflammation,and whether their combination could more effectively detect cognitive decline in CSVD.This study attempted to find more reliable,cost-effective,sensitive and convenient indicators to evalute cognitive impairment in patients with CSVD.MethodA total of 80 subjects who met the inclusion/exclusion criteria for cerebral small vessel disease(large artery problems were strictly excluded)were recruited between September 2021 and January 2023 and divided into a mild WMH group(score 1 to 3,40 subjects)and a severe WMH group(score 4 to 6,40 subjects)according to the severity of cerebral WMH according to the Fazekas scale,and 40 healthy subjects were recruited as controls.The subjects were fully informed when recruited.Within 24 hours of cranial MRI,the serverity of WMH was evaluated by Fazekas scale;blood samples were collected using EDTA tubes;The information of clinical examination and medical history was obtained;Evaluation of cognitive functions was performed by an experienced neuropsychological expert with the Mini-Mental State Examination(MMSE)and the Montreal Cognitive Assessment(MoCA).The normal score of MMSE scale depended on different education levels:illiterate 17;primary school>20;junior high school and above>24.The normal value of MoCA scale was 26.Serum NFL levels were measured by enzyme-linked immunosorbent assay twithin 24 hours of admission.We compared the clinical baseline levels among three groups and used the Nemenyi method to make multiple comparisons for non-normally distributed data.The correlation of serum NFL,neutrophil count(NC),neutrophil/lymphocyte ratio(NLR),platelet count x neutrophils/lymphocytes(Systemic Immune-Inflammation Index,SII),homocysteine(Hey)and other inflammatory markers with WMH and further with cognitive function was evaluated by spearman analysis in these patients.Finally,ROC curves were used to examine the efficacy of serum NFL level,or combined other inflammatory markers,or combined WMH in assessing cognitive impairment.ResultOf the 80 subjects who met the inclusion/exclusion criteria,only 76 subjects had complete data.Of the 40 healthy recruited controls,only 34 had complete data.The level of serum NFL,hs-CRP and Hcy,as well as Fazekas score for WMH and cognitive function score different significantly between the WMH group and the healthy control group(p<0.01).Multiple comparison analysis showed that the level of serum NFL(P<0.01),hs-CRP(P<0.01)and Hcy(P<0.01)were significantly higher in the severe WMH group than in the healthy control group but no significant differences were observed between the mild WMH group and the severe WMH group(P>0.05).Spearman analysis revealed that the serum level of NFL,hs-CRP and Hcy was correlated with WMH;there was also a correlation between serum NFL level and serum level of hs-CRP and Hey.Moreover,the serum level of NFL,hs-CRP and Hcy,and WMH were correlated with cognitive decline;WMH had a stronger correlation relative to other indicators.ROC curves were constructed using the indicators to evaluate their diagnostic value in cognitive decline:the highest AUC value of 0.898(95%CI:84.10%-95.51%)was obtained using the combination of serum NFL level and Fazekas score,followed by an AUC value of 0.877(95%CI:81.41%to 94.02%)using the Fazekas score alone and an AUC value of 0.863 for the combination of NFL level and inflammatory markers(95%CI:79.23%to 93.41%)and 0.848(95%CI:77.39%to 92.21%)for the AUC about the diagnosis of cognitive decline using NFL level alone.ConclusionThere was a correlation between the serum level of NFL and inflammatory markers,between the serum level of NFL or inflammatory marker and the severity of WMH,between the serum level NFL or inflammatory marker or WMH and cognitive decline in CVSD patients.The diagnostic value of serum NFL level in combination with WHM or serum inflammatory markers(hs-CRP and Hcy)in assessing cognitive decline was better than that of serum NFL level alone.Serum NFL levels can be used as a complement to the CSVD cognitive impairment imaging(WMH)assessment.