Application Of Total Cerebral Small Vessel Disease Burden Score In Community Elderly People And Patients With Carotid Artery Stenosi

Part 1Differences in cerebral grey matter volume and cerebral blood flow in cognitively normal elderly people with different cerebral small vessel disease total burden scoresObjective:To explore the differences of brain grey matter volume(GMV)and cerebral blood flow(CBF)in elderly people with normal cognition and different total burden scores of cerebral small vessel disease(CSVD).Methods:Retrospective analyses were conducted on 204 elderly subjects with normal cognitive function[Montreal Cognitive Assessment Scale(MoCA)score≥26 corrected for years of education].The three-dimensional isotropic T1-weighted sequence and pseudocontinuous arterial spin labeling(pCASL)sequence were applied for GMV and CBF analysis respectly.The MRI total CSVD burden score included cerebral microbleeds,lacunes,white matter hyperintensities and enlarged perivascular spaces.The total burden score ranged from 0-4.According to the results,a total burden score of 0-2 was determined as the mild to moderate burden group and 3-4 as the severe burden group.One-way analyses of covariance were used to compare the differences in regional GMV and CBF between the two groups of subjects,with multiple comparison correction.Results:Compared with those in mild to moderate total burden group,subjects in severe burden group had reduced GMV in bilateral fusiform gyrus,right superior temporal gyrus,left inferior frontal gyrus and left inferior lateral parietal regions,but enlarged GMV in bilateral striatum(caudate nucleus,putamen and pallidum)(all Padj<0.05).The severe burden group presented with widespread CBF reduction in cortical brain regions of the bilateral cerebral hemispheres except for bilateral insula and amygdala(Padj<0.05).Conclusion:Among elderly people with normal cognitive function,compared with those with mild to moderate CSVD burden,the ones with severe burden showed reduced GMV in some cortical brain regions and enlarged GMV in bilateral striatum and extensive hypoperfusion of cortical brain regions.These findings have implications for monitoring the health of older individuals,predicting changes in behavioural functions such as cognitive-emotional and deepening the understanding of cortico-striato-thalamic circuits.Part 2Correlation between total burden score,cognitive reserve and cognitive function in patients with cognitive impairment related to cerebral small vessel diseaseObjective:To investigate the correlation between MRI CSVD total burden scores and overall and cognitive domain cognitive function in patients with CSVD-related cognitive impairment,and to explore whether the association between testing cognitive reserve and cognitive change varies according to the degree of CSVD total burden.Methods:A total of 84 patients with CSVD-related cognitive impairment were enrolled for analysis,all satisfying a score of<26 on the MoCA scale.Patients were assessed with CSVD total burden,cognitive reserve scores,and neuropsychological scales.The MRI CSVD total burden score included CMB,WMH,EPVS and lacunes,with a total score range of 1-4.Cognitive reserve scores were analyzed by incorporating education level,marriage partnerships,occupational achievement,height,and hours of physical activity per week,with a range of 0-8.The overall cognitive assessment scale was scored using the MoCA;each cognitive domain was measured in five cognitive domains including orientation(orientation component of the MoCA scale),memory(Philadelphia Word Study Training-12 words),attention/executive function(Digit Breadth Test,Word Fluency Test),visuospatial function(Block Test)and language(Boston Naming Test).Cognitive domain scores were normalized to Z scores.Independent samples t-tests or Mann-Whitney U-tests were chosen to analyze differences in neuropsychological scales between groups.Spearman analysis was used to analyze the correlation between total CSVD burden,cognitive reserve scores,and the cognitive scales.Multiple linear regression models were chosen to investigate the association between CSVD total burden scores,cognitive reserve,and overall and cognitive domain Z-scores.Results:CSVD total burden scores were significantly negatively correlated with semantic fluency test(r=-0.366),czP(r)VLT-12 immediate recall(r=-0.330),delayed recall(r=0.327),and block test(r=-0.322)scores;cognitive reserve scores were significantly and positively correlated with MoCA(r=0.278),digit span forward(r=0.275),phonological fluency test(r=0.310),and semantic fluency test(r=0.336).After adjusting for demographic factors,Zattention/executive(β=-0.197),Zmemory(β=-0.218)and Zvisuospatial(β=0.220)functional domain scores decreased as total CSVD load scores increased;MoCA scores(β=0.638),Zattention/executive(β=0.194),Zmemory(β=0.150)and Zverbal(β=0.150)increased as cognitive reserve scores increased(P<0.05).The interaction items of total CSVD burden scores and cognitive reserve scores were substituted into the regression equation,and no significant relationship was found between the interaction items and each cognitive score(P>0.05).Conclusion:In patients with CSVD-related cognitive impairment,CSVD total burden score and cognitive reserve were independent influence factors on cognitive function changes.With increasing CSVD total burden,attention/executive,memory and visuospatial functions decreased.In contrast,better cognitive reserve protects overall cognitive function,attention/executive,memory and verbal function to some extent.Focusing on the concepts of pathological vascular brain injury and cognitive reserve is important for understanding the pathogenesis and slowing the progression of cognitive impairment associated with CSVD.Part 3Preliminary exploratory research on the relationship between cerebral small vessel disease total burden score,intraplaque hemorrhage and clinical symptoms in patients with carotid artery stenosisObjective:In patients with carotid stenosis,to investigate the relationship between carotid intraplaque hemorrhage(IPH)and total burden of cerebral small vessel disease(CSVD)and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods:A total of 108 patients(mean age 66±7 years,85.2%men)with unilateral carotid stenosis≥50%were enrolled for analysis.High-resolution vessel wall MRI sequences were applied to assess carotid IPH.The total CSVD burden score included white matter hyperintensities,lacunes,perivascular spaces,and cerebral microbleeds.The total burden score ranged from 0-4.Clinical symptoms including transient ischemic attack(TIA),amaurosis fugax,and ischemic stroke were recorded.The association between IPH and total CSVD burden was examined adjusted for other risk factors.The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested.Imaging features(CSVD score,IPH,degree of stenosis,and completeness of the circle of Willis)were correlated with clinical symptoms by Kruskal-Wallis H test,Chi-square test,and Fisher’ s exact test.Results:Multivariable logistic regression analysis showed that IPH(OR=2.98,95%CI 1.39-6.40,P=0.005)was independently associated with a higher CSVD score.The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference(P=0.004).Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients(P=0.004)and those with TIA/amaurosis fugax(P=0.008).The statistical difference was marginally significant between symptoms and IPH(P=0.057).No statistical difference was found between the symptoms and degree of stenosis and the completeness of circle of Willis(P>0.05).Conclusion:In patients with carotid stenosis,carotid IPH is associated with an elevated total burden of CSVD,and total CSVD score might be an imaging marker linked with clinical symptoms.