Effects Of Homocysteine On Cerebral Perfusion And Cognitive Function In Patients With Arteriosclerotic Cerebral Small Vessel Disease

Objective Homocysteine(Hcy)is a significant risk factor for arteriosclerotic cerebral small vessel disease(aCSVD),which is closely associated with the occurrence and development of aCSVD cognitive impairment,but the relevant mechanism remains unknown.There are few studies on the relationship between Hcy and aCSVD cognitive impairment in combination with multimodal Magnetic Resonance Imaging(MRI)technology.This study aims to explore the effect of Hcy on cognitive function in patients with aCSVD from the perspective of cerebral perfusion in combination with arterial spin labeling(ASL)technology and further understand the neural mechanism of cognitive impairment in aCSVD.Methods According to the Montreal Cognitive Scale(Mo CA),a total of 117 patients with aCSVD who visited the First Affiliated Hospital of Anhui Medical University from June 2020 to September 2022 were enrolled and divided into aCSVD with cognitive impairment group(aCSVD-CI,n=57)and aCSVD with non-cognitive impairment group(aCSVD-NCI,n=60).The cerebral blood flow(CBF)was surveyed by magnetic resonance cranial three-dimensional pseudo-continuous arterial self-selected marker(3D-p CASL)sequence scanning.All patients completed general data collection,serum Hcy measurement,and cognitive function,such as Mo CA,the Auditory Verbal Learning Test(AVLT),the Verbal Fluency Test(VFT),and the Stroop Color Word Test(SCWT).The multivariate logistic regression analysis was used to explore the risk factors for cognitive impairment in aCSVD.The CBF of the whole brain,gray matter and white matter and the perfusion in brain region of the two groups were compared.The correlation between gray matter CBF,serum Hcy,and CBF in brain region with differential perfusion and cognitive function scores was analyzed.The mediating effect model was used to analyze the role of CBF of gray matter in the relationship between serum Hcy and overall cognition.Results Serum Hcy levels were higher in the aCSVD-CI group than in the aCSVD-NCI group [16.38(14.02,18.58)μmol/L ratio 14.40(11.93,15.73)μmol/L,Z=-3.812,P<0.001].In terms of cerebral blood perfusion,in comparison to the aCSVD-NCI group,the aCSVD-CI group showed a significant descent in CBF in gray matter(Z=-3.217,P=0.001),the left middle frontal gyrus(t=-4.909,P<0.05),the right middle frontal gyrus(t=-5.137,P<0.05),and the right medial orbitofrontal lobe(t=-4.379,P<0.05).At the same time,CBF in the left hippocampus increased(t=4.575,P <0.05).After controlling for multiple risk factors,multivariate logistic regression showed that serum Hcy(B=0.246,P=0.001)levels were independent risk factors for cognitive impairment in aCSVD.Partial correlation analysis showed that the CBF of the left middle frontal gyrus(r=-0.389,P=0.006),the right middle frontal gyrus(r=-0.436,P=0.002),and the right medial orbitofrontal lobe(r=-0.429,P=0.002)were negatively correlated with the Stroop Color Word Test(SCWT)-C.CBF of the left hippocampus was negatively correlated with the Auditory Verbal Learning Test(AVLT)-long-delayed recall(r=-0.428,P=0.002).Mediation analysis showed that CBF of gray matter partly mediated the effect of Hcyy on overall cognitive function(indirect effect =-0.112,95%CI,-0.294--0.010,P<0.001).Conclusion Hcy is an independent risk factor for the development of cognitive impairment in aCSVD.The effect of elevated Hcy levels on aCSVD cognitive impairment may be achieved through changes in gray matter and regional brain perfusion.Hcy causes CBF regulation in different brain regions,generating corresponding functional cognitive impairment.