The Effect Of Vascular Risk Factors On The Default Mode Network In Mild Cognitive Impairment:the Resting-stating Functional Magnetic Resonance Imaging Study

BackgroundAlzheimer's disease(AD)is a progressive,degenerative disease with an insidious onset,and AD is the most common type of dementia in the elderly.Mild cognitive impairment(MCI)is considered as a transitional stage of normal aging and senile dementia,and has been confirmed as a high risk group of AD.The cause is not known,but it is thought to be the result of a combination of genetic and environmental factors.The studies have found that vascular risk factors(VRFs)were associated with cognitive decline and AD pathogenesis,promoting the occurrence and development of AD.Resting-state functional magnetic resonance imaging(rs-fMRI),with its unique advantages,have wide application in AD research.The default mode network(DMN)as a core part of the resting-state networks,plays an irreplaceable role in early diagnosis,monitoring,therapeutic observation in AD-related diseases.Little is known about the potential impacts of VRFs on the DMN and their underlying neural substrates in MCI patients.Therefore,to explore how VRF influence the neural network mechanism of MCI patients,can provide a new idea for early diagnosis,timely intervention and delay the progress of AD.ObjectivesTo explore the potential effect of VRF on DMN in MCI patients by rs-fMRI based on the seed point.Methods128 elderly Han Chinese participants(67 MCI subjects and 61 matched normal elderly or healthy control(HC))with or without VRFs(hypertension,diabetes mellitus,hypercholesterolemia,smoking and alcohol drinking)underwent the rs-fMRI and neuropsychological tests.According to the VRF burden,the subgroups were as follows:MCI(NVRF= 24,VRF1=21,VRF>1=22),HC(NVRF=16,VRF1=20,VRF>1=25).We obtained the default mode network(DMN)to identify alterations in MCI with the varying number of the VRF and analysed the significant correlation with behavioral performance.ResultsRegions related to the main effect of disease were observed in right parahippocampal gyrus and bilateral middle temporal gyrus and middle cingulate gyrus,while the main effect of VRF was detected in right superior frontal gyrus and left precuneus.Additionally,effects of diseasexVRF interaction was primarily in bilateral dorsolateral prefrontal cortex(DLPFC)(i.e.,middle frontal gyrus).We found an intriguing pattern about the relation between executive function(subdomain:Similarity)and altered function connectivity of posterior cingulate cortex(PCC)within the left DLPFC.Firstly,in HC-VRF>1 subgroup,the left DLPFC was significantly negatively correlated with performance on the Similarity(r=-0.512,p=0.018).And then,the left DLPFC displayed significantly negative relation to the performance of the Similarity(r=-0.539,p= 0.014)in MCI-NVRF subgroup.When MCI with VRF1,the alteration of PCC with the left DLPFC was positively correlated with the changes in Similarity scores(r= 0,537,p= 0.026).Furthermore,significantly negative correlation between Similarity scores and increased functional connectivity was found in MCI subgroup with VRF>1(r=-0.482,p= 0.043).ConclusionThese findings suggested that the dose-dependent effects of VRF on DLPFC were highlighted in MCI,and the dynamic compensatory neural processes fluctuated with variation of VRF loading may be a key role in the progression of MCI.