Multimodal Magnetic Resonance Imaging Study Of Early Cognitive Impairment In Poststroke Patients With Cerebral Small Vessel Disease

Object:Cerebral small vessel disease?CSVD?is one of the most common causes of vascular cognitive impairment?VCI?.The subcortical VCI related to CSVD is homogenous,with insidious onset,gradual development and is lack of specific treatment.We conducted a study on Renji CSVD cohort,using a comprehensive battery of neuropsychological tests with multimodal MRI examinations to probe the characteristics of early cognitive impairment in these patients.The correlations between cognition with different imaging measures of CSVD were analyzed to reveal the mechanism of the occurrence and development of VCI due to CSVD.Method:Participants were recruited from the stroke clinic at the Department of Neurology,Renji Hospital,an affiliated teaching institution of School of Medicine,Shanghai JiaoTong University from June 2015 to February 2018?Renji Cerebral SVD Cohort Study,RCCS,http://www.clinicaltrials.gov,NCT01334749?.Healthy elderly matched by age,gender and education with CSVD patients were also enrolled from Tangqiao community,Pudong new district in Shanghai.Demographics such as gender,age,years of education as well as spectrum of vascular risk factors?VRFs?were recorded for each participant.MRI sequences were obtained including T1 weighted imaging?T1WI?,T2 weighted imaging?T2WI?,T2-fluid attenuated inversion recovery?T2-FLAIR?and diffusion tensor imaging?DTI?.All participants were dignosed as mild cognitive impairmet?MCI?,no cognitive impairment?NCI?or normal control?NC?group after finishing all neuropsychological tests.Semi-quantitative visual rating scales of MRI structural lesions were assessed,including Fazekas score for white matter hyperintensity?WMH?,the number of lacunes,the number of cerebral microbleeds?CMB?and the number of enlarged perivascular spaces?EPVS?.Staal's SVD score was calculated combining all the above mentioned four structural lesions.Quantitative measures such as WMH volume,structural brain network measures and DTI measures including FA?fractional anisotropy?,MD?mean diffusivity?and PSMD?peak width of skeletonized mean diffusivity?were also analysed.The group difference of multiple imaging parameters was compared.The relationships between multimodal imaging measures and cognition were examined to reveal the mechanism of occurrence and development of cognitive impairment of CSVD.Results:?1?Part 1:Aanlysis of structural MRI:There were significant cognitive differences between MCI and NCI group,including general cognition:mini-mental state examination?MMSE?and the Montreal Cognitive Assessment?MoCA?,and all tests of different cognitive domains?all p<0.05?.There was no statistically significant difference on the Fazekas score between the two groups?p=0.09?,however,WMH volume was different between the two groups?p=0.004?.There was no correlation between Fazekas score and cognitive scores in any of the tests of different cognitive domains?all p>0.05?,while whole brain WMH volume was significantly correlated with tests of executive,memory,visual-spatial and language function?all p<0.05?.Further analysis of the correlation between the deep brain WMH volume or the periventricular WMH volume with different cognitive tests scores was conducted.The results showed that the WMH volume in the periventricular regions was correlated with Trial making test-B?TMT-B??r=0.232,p=0.014?,Stroop Word Test C?SCWT-C??r=0.202,p=0.034?,Digital Symbol Substitution Test?DSST??r=-0.272,p=0.004?,and Auditory Verbal Learning Test Short term free recall?AVLT-4??r=-0.240,p=0.011?,Auditory Verbal Learning Test Long term free recall?AVLT-5??r=-0.257,p=0.007?,Rey-O Complex Figure Test copy?RCFT copy??r=-0.368,p<0.001?.There were also significant correlation between deep WMH volume and tests of executive function or visual-space function,but no correlation was found between deep WMH volume and tests of memory or language function.?2?Part 2:DTI Analysis:There were significant differences in the general cognitive scores?MMSE and MoCA?among the three groups?p<0.001?.There were no significant differences in general cognitive scores between NCI and NC group?p>0.05?.Significant differences in the different cognitive domains were found among the three groups.Post-hoc analysis showed significant differences existed between MCI and NCI group?all p<0.05?or between MCI and NC group?all p<0.05?,but not between NCI and NC group.However,DSS and VFT scores were different between every two groups.There were significant differences in DTI measures among the three groups?all p<0.001?.After adjusting for age,gender,years of education and vascular risk factors,FA had no significant correlation with tests scores of general cognition or tests scores of any cognitive domain?p>0.05?,MD was significantly correlated with SCWT-C and showed no significant correlation with other cognitive tests,while PSMD was positively correlated with TMT-B,SCWT-C,and was negatively correlated with DSST,AVLT4 and AVLT5.There was no correlation between PSMD and test scores of language or visual spatial function?p>0.05?.Logistic regression analysis showed that PSMD had a significant impact on cognitive status?OR=0.581,95%CI=0.367⁰.919,P=0.02?,while FA and MD had no significant impact on general cognition?P>0.05?.?3?Part 3:Structural brain networks analysis:There were significant differences between MCI and NCI group in multiple cognitive tests.E_Globallobal significantly correlated with most neuropsychological tests?p<0.05?,while no significant correlation was found between the SVD score and any of the neuropsychological tests.Binary logistic regression found that only E_Globallobal had a significant effect on the cognitive status of CSVD patients?OR=0.41,95%ci:0.22-0.74,p=0.003?,while SVD score had no significant effect on the cognitive status of CSVD patients?OR=1.11,95%CI:0.72¹.71,p=0.650?.The mediation analysis showed that SVD score had a significant standardized total effect on cognitive function?p=0.013?,and also had a significant standardized indirect effect?p=0.016?.However,the standardized direct effect of CSVD structural damage on cognitive function was not significant?p=0.097?.Conclusions:?1?Patients with CSVD has exhibited a wide range of cognitive decline in the early stage of the disease.Cognitive impairment due to CSVD was closely related to WMH.Quantitative WMH volume was more sensitive detecting the early cognitive impairment compared to Fazekas score.Besides,periventricular WMH was more related to cognitive decline compared to deep WMH.?2?Compared with FA and MD,the new DTI measure PSMD was more sensitive and reliable to detect the early cognitive impairment in patients with CSVD.As a fully automated calculated DTI measure,PSMD might be a new surrogate marker for CSVD cognitive impairment.?3?Compared with SVD score,structural brain network measures were significantly correlated with cognitive dysfunction in this cohort of post-stroke CSVD patients.The mediation analysis indicated that brain network disruption was a mediating factor between CSVD structural lesions and cognitive impairment.Structural lesions lead to the cognitive decline by interrupting the integrity of the brain network.This study provided some evidence for the mechanism of early cognitive impairment in patients with CSVD.