Correlation Between Neurofilament Light Chain And Post-stroke Cognitive Impairment

Background:The disease and economic burden of stroke is growing rapidly,with an early onset and a large number of people affected by the disease,making it the leading cause of disability and death in China.Post-stroke cognitive impairment(PSCI)is one of the common complications of stroke,severely affecting neurological recovery and survival time,and is an important cause of death and disability in stroke.Plasma neurofilament light chain(NFL)is a marker of axonal injury and neurodegenerative disease.Studies have shown that increased levels of NFL predict functional improvement after stroke and can be used as a biomarker for long-term prognosis in ischaemic stroke,but it is not known whether NFL predicts the risk of PSCI.The aim of this study was to investigate the association between NFL and the occurrence of PSCI in a multicentre,larger population-based ischaemic stroke cohort.Methods:The study was conducted in patients with acute ischaemic stroke who participated in The China Antihypertensive Trial in Acute Ischemic Stroke(CATIS).Seven of the hospitals were randomly selected to conduct a study on the effect of acute blood pressure lowering on cognitive function after stroke before the CATIS subjects were randomised.7 of the 26 hospitals were randomly selected using a simple random sampling method.Of these 7 hospitals,660 patients were selected on a continuous basis,excluding deaf,blind,severely aphasic and other patients who were unable to complete or cooperate with the cognitive function scale.By November 2012,enrolment was completed.80 to 100 patients were enrolled in each hospital on a continuous basis.During the 3-month post-onset follow-up period,15 subjects were lost to follow-up and 7 died,with the final 638 subjects completing the cognitive functioning status assessment and eventually being included in this study.Within 24 hours of admission,blood samples were collected from patients to assess their level of self-care(Modified Rankin Scale)and stroke severity(NIHSS scale)using information on patient demographics,lifestyle,personal history of disease and family history of stroke.Cognitive function was assessed at 3 months post-onset using the Mini-mental state examination(MMSE)and the Montreal cognitive assessment(Mo CA)to determine whether a PSCI had occurred.The normal criteria for the MMSE scale were:illiteracy≥17;primary school≥20;junior high school and above≥24;and the normal criteria for the Mo CA scale were:≥26.Plasma NFL concentrations were measured by electrochemiluminescence immunoassay within 24 hours of the patients’admission to the hospital.Plasma NFL concentrations were included in logistic regression models as continuous variables,and as categorical variables based on median grouping,respectively,to analyse the association between plasma NFL and PSCI at admission and the strength of the association.Results:(1)A total of 638 patients with acute ischaemic stroke were included in this study,with patients in the high concentration group aged61.89±10.78 years older than those in the low concentration group aged58.31±9.70 years(t=4.410,P<0.001).At 3 months post-onset,the Mo CA score 21(16-25)and MMSE score 26(21-28)were lower in the high concentration group than in the low concentration group with 22(18-26)and 27(23-29)(Z=2.490,P=0.013;Z=2.76,P=0.006).(2)Using the Mo CA scale score as the basis for PSCI,the incidence of PSCI was 76.17%.77.43%of patients in the NFL high concentration group and 74.92%in the low concentration group had PSCI,with no statistically significant difference between the two groups(x~2=0.553,P=0.457).The inclusion of NFL concentration as a continuous variable and a categorical variable based on median grouping into logistic regression models respectively showed no significant correlation between plasma NFL levels and PSCI.(3)The incidence of PSCI was 21.94%using the MMSE scale score as the basis for PSCI.25.7%of patients in the high NFL concentration group and 18.2%in the low concentration group had PSCI,with a statistically significant difference between the two groups(x~2=5.271,P=0.022).In univariate analysis,the risk of PSCI was 1.557 times greater in the high NFL concentration group than in the low concentration group(95%CI:1.065-2.276,P=0.022);after adjusting for possible confounders,NFL concentration was not statistically associated with the risk of PSCI(P>0.05).In stratified analysis,the risk of PSCI was 2.088 times greater in the high NFL concentration group than in the low concentration group in study subjects with an m RS score of 0-2(95%CI:1.089-4.003)and remained statistically significant after multifactorial adjustment(OR=2.459,95%CI:1.152-5.247).Conclusions:There was no significant correlation between acute plasma levels of NFL and the risk of PSCI at 3 months in patients with acute ischaemic stroke,but the risk of moderate and higher cognitive impairment was significantly higher in the group with high levels of NFL in patients with an admission m RS score of 0-2.