| Objective: Neurofilament light chain(Nf L)is a promising predictive biomarker of active axonal injury and neuronal degeneration diseases.Cerebral small Vessel Disease(CSVD)refers to the disease caused by small blood vessels in the brain,including small arteries,venules and capillaries.The imaging manifestations contains lacunar infarct(LI),white matter hyperintensity(WMH),cerebral microbleed(CMB)and enlarged perivascular space(EPVS).CSVD is very common in the elderly and is strongly associated with the increased risk of stroke and dementia.Therefore,we speculate that plasma Nf L plays specific roles in predicting and monitoring CSVD progression.Considering the significant clinical and societal implications as well as prevalence of CSVD,we evaluated if an increase in plasma Nf L levels could play a monitoring role in the progression of cerebral small vessel disease(CSVD)among the non-demented elders in the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database.Methods: The study included 496 non-demented participants from the ADNI database.All participants underwent plasma Nf L measurements and 3.0-Tesla Magnetic Resonance Imaging(MRI)of the brain;387(78.0%)underwent longitudinal measurements.Blood samples were detected and analyzed using ultrasensitive single-molecule array(Simoa)technology.We downloaded the imaging data at baseline and follow-up,and manually measured the number of CMBs,LIs,and volumetric WMHs as well as Fazekas scores.CSVD burden was assessed using simple CSVD scores,including CMBs,Fazekas score,and LIs.As for simple MRI score,one point each was scored for the presence of CMBs,a Fazekas score of ≥ 2,and a LI count of ≥ 3,resulting in a minimum score of 0 and a maximum score of 3.Total CSVD burden scores were then categorized into three groups according to the simple CSVD score: none(0 points),mild(1 point)and moderate–severe CSVD(2-3points)groups.The progression of CSVD burden and markers were defined as if there was an increase in simple MRI score,CMB counts,Fazekas score,and LIs counts during follow-up.Cross-sectional and longitudinal associations between CSVD burden and Nf L levels were evaluated using multivariable-adjusted models.Results: Plasma Nf L was higher in the moderate–severe CSVD burden group(45.2 ±16.0 pg/m L)than in the non-burden group(34.3 ± 15.1 pg/m L)(odds ratio [OR] =1.71,95% CI = 1.24-2.35)at baseline.Nf L was positively associated with the presence of CMBs(OR = 1.29,95% CI = 1.01-1.64),LIs(OR = 1.43,95% CI = 1.06-1.93),and moderate–severe WMHs(OR = 1.67,95% CI = 1.24-2.25).Longitudinally,a higher change rate of Nf L could predict more progression of CSVD burden(OR = 1.38,95% CI = 1.08-1.76),WMHs(OR = 1.41,95% CI = 1.10-1.79),and LIs(OR = 1.99,95% CI = 1.42-2.77).Conclusions and Significance: Our study comprehensively evaluated the associations of plasma Nf L levels on the CSVD.The primary results showed that increased plasma Nf L concentration was linked to higher risk of CSVD prevalence at baseline and CSVD progression at follow-up.These findings indicate that plasma Nf L is a dynamic biomarker of CSVD progression in non-demented elders,especially those with normal cognitive function.Therefore,our study offers an available noninvasive blood-based tool to monitor longitudinal CSVD change and understand the future trend of CSVD change.Plasma Nf L level is a valuable non-invasive biomarker that supplements MRI scans and possibly reflects the severity of CSVD burden.Notably,high plasma Nf L levels tend to represent an increased CSVD risk,and dynamic increases in Nf L levels might predict a greater progression of CSVD. |
