Study On The Deep Medullary Vein And Brain Structure Imaging And Functional Change

Part Ⅰ:Temporal and Spatial Patterns of Structural Abnormalities in Cerebral Small Vein DiseaseBackground and purpose:Cerebral small vessel disease(CSVD)has long been classified as a category of small vessel disease,while the mechanism of cerebral small venules’disease is poorly understood.We speculate that a combination of venous drainage obstruction and amyloid clearance leads to complex brain structural damage patterns.This study aims to explore the temporal and spatial patterns of damage to the deep medullary vein(DMV),white matter,gray matter,and amyloid clearance in a large community population,to further understanding the occurrence and development of cerebral small venules’ disease.Methods:We included participants in the Shunyi cohort study with complete baseline MRI,which included T1,SWI,and diffusion tensor imaging(DTI)sequences,was completed with good quality.A 5-yearsFollow-up MRI was conducted.The number of DMVs was obtained by visual assessment of SWI images;the white matter hyperintensity(WMH)volume and brain volume parameters were automatically segmented from 3D-T1 using SPM and Freesurfer;DTI parameters were obtained using FSL.The Aβ40,Aβ42,and Aβ42/40 concentrations in baseline and follow-up plasma samples were measured.We analyzed the relationship between DMV number and brain structure parameters was analyzed using mediation models.Using the tract-based spatial statistics(TBSS)tool,we analyzed the linear correlation between DMV number and DTI parameters.Using CAT12 and freesurfer,we performed and voxel/surface-based analysis on the correlation between DMV number and brain atrophy.Results:The baseline analysis included 977 participants(average age 56.8 years,34.7%male),of which 544 received complete MRI follow-up(mean follow-up time 5.56 years).The results showed that the reduction in DMVs was associated with widespread white matter microstructure damage(DMV number and fractional anisotropy β=0.000863,SE=0.000176,p<0.001)and progressed faster in deep white matter.More importantly,the reduction in DMV number was stably and strongly correlated with global brain atrophy(DMV number and brain parenchyma fraction β=0.03,SE=0.001,p<0.001),which was distributed in bilateral temporal lobes,hippocampus,and other regions.White matter microstructure damage played an intermediate role in deep medullary vein-induced brain atrophy.The pattern of brain structure changes showed bidirectional features at different stages of the development of deep medullary vein damage,indicating different pathogenic mechanisms.Conclusion:Deep medullary vein damage leads to widespread damage to white matter and gray matter structures,with multiple mechanisms involved in disease progression.Part Ⅱ:Investigation of the Relationship between Deep Medullary Veins Damage and CognitionBackground and Purpose:The relationship between cerebral small vessel pathology and neurodegenerative diseases has been recognized.We hypothesize that cerebral small venules’ disease may lead to cognitive decline as a core clinical feature at the functional level,but the relevant evidence is lacking.This study aimed to explore the relationship between the deep medullary vein(DMV)damage and cognitive function as well as dementia in a large sample community population with long-term follow-up,and to analyze the role of brain structural parameters in these associations,in order to further reveal the clinical symptom characteristics and pathogenic mechanisms of cerebral small venules’ disease.Methods:Participants in ShunYi study that completed comprehensive baseline neuropsychological evaluations in the Shunyi cohort were included in this study.These evaluations included the Mini-Mental State Examination,Montreal Cognitive Assessment,Fuld Object Memory Evaluation,rapid verbal retrieval(RVR),Block Design Test,and Digit Span Test,and cognitive follow-up was conducted four years later.Multiple linear regression was used to analyze the correlation between the number of s(DMVs)and brain structural parameters,and multiple logistic regression was used to analyze whether the number of DMVs predicts dementia and MCI.Mediation analysis was used to analyze the effect of brain structural indicators and plasma amyloid protein concentration in the association between the number of deep medullary veins and cognition.Results:We included 1040 participants the baseline analysis(mean age 56.8 years,34.7%male),of whom 895 received complete cognition follow-up(mean follow-up time 4.33 years),and there were 31 and 59 new-onset dementia and MCI,respectively.In the univariate model,a decrease in the number of deep medullary veins was significantly associated with an increased risk of dementia(OR=0.683,95%CI=0.500-0.934,P=0.017).The reduced number of deep medullary veins was also associated with poorer performance in RVR test(β=0.65,SE=0.17,P<0.001),independently of age,sex,years of education,and vascular risk factors,but no significant progression was observed during follow-up.In the mediation analysis,white matter microstructural damage mediated the association between DMVs number and RVR score.Conclusion:Reduced number of DMV is associated with poorer executive function,is mediated by white matter microstructural damage.However,the causal relationship could not be validated in longitudinal analysis.