Changes Of Plasma Markers And Their Relationship With Microstructure Of White Matter In Patients With Mild Cognitive Impairment

Objective To investigate the changes of plasma β-amyloid(Aβ),phosphorylated tau(p-tau),total tau(t-tau)and neurofilament light chain(NFL)in patients with amnestic(aMCI)and vascular mild cognitive impairment(vMCI),as well as the relationship between plasma Aβ42/40 and the microstructure of white matter(WM).Methods 36 aMCI patients,20 vMCI patients and 34 healthy controls(HC)who attended the outpatient and inpatient department the Department of Neurology of the First Affiliated Hospital of Anhui Medical University from August 2020 to April 2022 were included,and the three groups of participants were matched by gender,age and education level.All participants were assessed on neuropsychological scales,including the Mini-Mental State Examination(MMSE),the Montreal Cognitive Assessment(MoCA),and the Activity of Daily Living Scale(ADL);The blood samples of all subjects were collected and the plasma Aβ42,Aβ40,t-tau,p-tau181,p-tau217,NFL levels and APOE genotype were detected;All participants underwent magnetic resonance scans to obtain diffusion tensor imaging(DTI)data;The DTI index of 48 WM regions of each individual were obtained using a region of interest(ROI)-based DTI analysis method(based on the ICBM-DTI-81 white matter map developed by Johns Hopkins University),including fractional anisotropy(FA)and mean diffusivity(MD).The cognitive function,plasma Aβ42,Aβ40,Aβ42/40,t-tau,p-tau181,p-tau217,NFL levels and DTI index of the three groups were compared,and the correlation analysis was made between the plasma Aβ42/40 levels and DTI index of aMCI and vMCI.Results The MMSE and MoCA scores of aMCI and vMCI were significantly lower than those of HC(all P<0.001).There was no significant difference in ADL scores among the three groups(all P>0.05).There were no significant differences in plasma levels of Aβ42,t-tau,p-tau181 and NFL among the three groups(all P>0.05);The plasma Aβ40 level of vMCI was statistically higher than that of HC(P<0,05),aMCI was not significantly increased compared with HC(P>0.05);Either in the aMCI group or the vMCI group,there was no statistically significant difference in plasma Aβ42/40 levels compared to the HC group(all P>0.05),the plasma Aβ42/40 of vMCI was significantly decreased compared with aMCI(P<0.05);The plasma level of p-tau217 in the aMCI group was statistically higher than that in the HC group and the vMCI group(P<0.05),but there was no significant difference between vMCI and HC groups(P>0.05).Compared with HC and aMCI,the FA of the left anterior limb of internal capsule of vMCI were significantly lower than those of HC and aMCI(all P<0.05).The MD of the left superior corona radiata,left external capsule,left cingulum(cingulate gyrus)and left superior fronto-occipital fasciculus in the vMCI group were significantly higher than those in HC and aMCI groups(all P<0.05),while the MD of the right posterior limb of internal capsule and left cingulum(hippocampus)of aMCI and vMCI were significantly higher than those of HC(P<0.05).In aMCI,plasma Aβ42/40 levels were positively correlated with FA of left posterior limb of internal capsule(r=0.403,P=0.015)and negatively associated with MD of the right fonix(r=-0.395,P=0.017);In vMCI,plasma Aβ42/40 levels were mainly positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule(r=0.575,P=0.008;r=0.639,P=0.002).It was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule(r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusion The levels of plasma Aβ40、Aβ42/40、p-tau217 in patients with aMCI and vMCI were different: plasma Aβ40 of vMCI patients was significantly increased compared with HC,plasma Aβ42/40 of vMCI patients was significantly decreased compared with aMCI patients,plasma p-tau217 level of aMCI patients was significantly increased compared with HC and vMCI patients.There are differences in the regions of impairment of WM microstructural integrity in the early stage of different dementia types,mainly in the cingulum,corona radiata,internal capsule,external capsule,etc.Plasma Aβ42/40 levels in patients with aMCI and vMCI were associated with the destruction of WM structural integrity,and there is regional specificity between them,with aMCI mainly in the fornix and vMCI mainly in the superior cerebellar peduncle and anterior limb of internal capsule.