Correlation Between Structural And Functional Imaging And Cognitive Impairment In Patient With Subcortical Ischemic Vascular Disease

Vascular dementia (VaD) is the second most common form of dementia,following Alzheimer disease (AD), in the elderly.Vascular cognitiveimpairment (VCI) is a new concept based upon early cognitive impairmentcaused by cerebral vascular disease,which was introduced to identify earlystage cognitive decline for valid treatment by Hachinski and Bowler in1993.VCI as a diagnosis ranges from early cognitive decline to dementia,whichforms a spectrum that includes VaD, mixed AD with a vascular component,and VCI without dementia.Subcortical ischemic vascular dementia is a more homogenous subtype ofVaD with typical extensive periventricular white matter lesions,which isprogressed from subcortical ischemic vascular disease(SIVD).In addition, thecortex is usually unaffected.The primary etiological mechanism responsiblefor SIVD is small vessel disease.Small vessel disease can lead to lacunarinfarction states and white matter lesions,which are found mainly insubcortical areas.White matter tracts control message transduction amongdifferent cortical centers.Subsequently, white matter lesions can decreasecommunication accuracy and nerve conduction velocity,which are associatedwith cognitive dysfunction in subcortical ischemic vascular dementia patients.Subcortical ischemic vascular dementia is considered as a model for VCIbecause its well-defined diagnostic criteria allow identification of ahomogeneous category,which improves VCI diagnosis and treatment.Various imaging techniques have been used to evaluate brain changesassociated with VaD. White matter lesions cause cerebral white mattershrinkage in the later stage in SIVD.The white matter atrophy can bemeasured by using MRI. DTI can detect microstructural integrity of white matter by measuring thedirectionality of molecular diffusion(fractional anisotropy,FA)and the averagemotion of water molecules(mean diffusivity,MD),which can not be measuredby conventional MRI.we can investigate impairment of cognition by detectingthe integrity of cognition related tracts which,such as CC,CF,fornix,SLF, aredirectly related to cognitive function in SIVD patients.Magnetoencephalography (MEG) is considered a more sensitivetechnique compared to morphological imaging in cognitive impairmentbecause it directly provides information regarding the electrophysiologicalchanges of cortical neurons.MEG relies on neuromagnetic signals thatpenetrate the skull and scalp without distortion. Moreover the superconductingquantum interference device (SQUID) detects magnetic field with highsensitivity.As a result of this technology, we can acquire relatively directinformation about white matter tract transduction in SIVD.White matter tracts underlying primary somatosensory and auditorycortex are damaged similarly to white tracts underlying cortex associated withcognitive decline.We can measure changes in somatosensory evoked magneticfield (SEF) and auditory evoked magnetic field (AEF) by MEG and theirrelationship with cognitive impairment in SIVD patients.The following3parts were designed to study white matter atrophy byconventional MRI, microstructural integrity of cognitive related tracts byDTI,alternation of cerebral evoked magnetic field by MEG and theircorrelation with cognitive function impairment in SIVD.Part1：Correlation between cerebral structure imaging and cognitiveimpairment in patients with subcortical ischemic vasculardiseaseObjective: To Summarize neuropsychological characteristics of SIVDpatients by using a set of Neuropsychological tests.To investigate thecorrelation between vascular cognitive impairment and indexes of cerebralstructure imaging in MRI.Methods: according to the MRI criteria of Erkinjuntti(2000),45SIVD patients were recruited.The patients were divided into VaD(24) andV-CIND(21) group.All participants,including SIVD patients and22normalelderly controls(NC) matched in age and gender,were givenneuropsychological tests to assess their cognitive status.Mini-Mental StatusExamination(MMSE) and Montreal Cognitive Assessment(MoCA) were usedin evaluating global cognitive status.Memory function and attention wereevaluated with Digit Span Test(DST).Language function were assessed withVerbal fluency Test(VFT).Visuospatial function was assessed with ClockDrawing Test(CDT).Executive function was evaluated with Trail MakingTest(TMT). White matter lesions(WML) were assessed by MRI linearmeasurement and Age-related white matter change rating scale that isdeveloped by Wahlund. Temporal lobes of participants were scaned using3D-T1FSPGR equences and hippocampal volume was measured bythree-dimensiona semiautomated volumetric method.Correlation analysis wasperformed to investigate the correlation between vascular cognitiveimpairment and indexes of cerebral structure imaging in MRI.Results:1The scores of neuropsychological scale were significantly decreased inMMSE,MoCA,CDT,DST and VFT in V-CIND group as compared to NCgroup(P<0.05).And the scores of TMT was increased(P<0.05).VaD subjectswere worse than that of the V-CIND and NC subjects(P<0.05).2Compared with NC group, Huckman index(HI) and the third ventricwidth(TVW)were increased(P<0.05).Front horn index(FHI)and ventricleindex(VI)were decreased in VaD subjects(P<0.05).There was significantstatistical difference between the V-CIND group and VaD group in HI,FHI andVI(P<0.05).3The mean WML rating scores in VaD group(13.19±2.06) and V-CINDgroup(11.76±2.23) were higher than NC group(2.37±1.49,P<0.05).Significant statistical difference of that was not found between VaD group andV-CIND group(P>0.05).As to each regions,VaD patients had increased scoresin frontal area and parieto-occipital area than NC(P<0.05).There was obvious increase in frontal area and parieto-occipital area in V-CIND group than in NCgroup(P<0.05).The VaD group’s WML rating scores in frontal area andparieto-occipital area were higher than that of V-CIND group(P<0.05).4Significant statistical difference of that was not found in themeasurement of hippocampal volume among VaD group,V-CIND group andNC group. The hippocampal volume of VaD were (3.73±0.75cm3) in lefthemisphere and (3.82±0.86cm3) right hemisphere.Conclusions：1The cognitive impairment of SIVD patients are deteriorated,especifically in executive and visuospatial function.The degree of WML is isclosely related to that of the cognitive function impairment in SIVDpatients,which will be the most serious in the VaD stage.2The linear measurements of WML in frontal are related with cognitiveimpairment in SIVD patients,which usually be detected in the late stage.3Obvious atrophy in hippocampus is not found in the Atrophy,which canbe applied in differential diagnosis of SIVD and AD.Part2：Correlation between cognitive related tracts DTI and cognitiveimpairment in patients with subcortical ischemic vasculardiseaseObjectives: To measure fasciculus of cognition related structure by usingdiffusion tensor imaging(DTI) technique in patients with SIVD.To investigatethe correlation between cognition related tracts and cognitive impairment inSIVD patients.Methods: SIVD patients were recruited according to the MRI criteria ofErkinjuntti(2000). DTI images were applied to16VaD patients,15V-CINDpatients and17NC which matched in age and gender.The values of fractionalanisotropic(FA) and mean diffusivity(MD) in splenium of corpuscallosum(SCC),genu of corpuscallsum(GCC),fornix,anterior cingulate fasciculus(ACF),posterior cingulate fasciculus(PCF) and superior longitudinal fasciculus(SLF)were detected as indexes of tracts injury.Neuropsychological tests were givento all participants to assess their cognitive status.The correlation between vascular cognitive impairment and the values of FA and MD in fasciculus ofcognition related structure was analyzed by correlation analysis.Results:1Patients with V-CIND had reduced scores in MMSE, MoCA,CDT,DST,VFT and increased time consumping in TMT as compared withNC.VaD patients had the worst performance in the three groups.2Compared with NC group, patients with VaD had lower FA value inFornix,GCC,SCC,ACF,PCF and SLF.And patients with V-CIND had lower FAvalue inGCC,ACF,PCF and SLF than NC group.3VaD patients demonstrated increased MD value in Fornix,GCC,SCC,ACF and SLF as compared with NC group.V-CIND patients had higher MDvalue in Fornix than NC group.4Correlation analysis between DTI indexes of tracts of cognition relatedstructure and cognitive impairment were performed in all anticipants.FAvalues in Fornix,GCC,SCC,ACF,PCF,SLF and MD values in Fornix,GCC,SCC,ACF,SLF correlated with global cognitive function (MMSE,MoCAscore).FA values in GCC and MD values in GCC,ACF correlated with TMTscores.FA values in fornix,GCC,ACF and MD values in GCC correlated withCDT scores.FA values in Fornix,ACF,PCF,SLF and MD values in Fornix,ACF,PCF,SLF correlated with DST values.FA values in GCC,ACF,SlF and MDvalues in GCC,SLF correlated with VFT values.Conclusions：1tracts of cognitive structure are impaired in SIVD patients.Theseleisions are mainly presented in GCC and ACF.DTI is useful in detecting theselesions.2Integrity of cognitive structure tracts is closely related to impairment ofcognitive function in several cognitive areas.3DTI can detect integrity of cognitive structure tracts sensitively andobjectively,which can be regard as a index to monitor cognitive impairment inSIVD patients,especial in early detection and disease evaluation. Part3：Magnetoencephalography assessment of evoked magnetic fieldand cognitive function in subcortical ischemic vascular diseasepatientsObjective：To investigate the relationship between cognitive impairmentand somatosensory evoked magnetic field and auditory evoked magnetic fieldchanges in elderly male patients with SIVD.Methods: Magnetoencephalography (MEG) was used to recordsomatosensory evoked magnetic field and auditory evoked magnetic fieldchanges from4VaD patients (76–88years),3patients with vascular cognitiveimpairment with no dementia (V-CIND;74–87years), and6healthy volunteers(72–85years) which matched in age and gender.Latency peaks, equivalentcurrent dipole (ECD) strength, and bilateral ECD position were recorded. TheMEG data were superimposed on magnetic resonance imaging to producemagnetic source imaging.The correlation between vascular cognitiveimpairment and somatosensory evoked magnetic field and auditory evokedmagnetic field changes by correlation analysis to provide objective basis ofcerebral evoked magnetic field changes in SIVD patients.Results：1Three wave peaks were observed in the SEF wave at M20, M35, andM60.Research shows that the M20originating from the primary sensorycortex is the most prominent peak in SEF and is a stable and repeatablemeasure.Compared to controls,VaD patients showed delayed M20latency andincreased ECD strength.There were no significant differences in M20inter-hemispheric positions across diagnostic categories.Compared to controls,V-CIND patients showed delayed M20latency.And the ECD strengthincreased but significant differences were not found.Significant differences inM20inter-hemispheric positions were not found,too.Correlation analysisshowed that there was a correlation between M20latency and scores ofMMSE、MoCA,TMT-a,TMT-b,CDT,DST (backwards),VFT. And M20ECDstrength correlated with MMSE,MoCA,TMT-a,TMT-b,CDT,DST(backwards).2M100, originating from Heschl’s gyrus, is the most prominent peak in AEF, and we used this value to evaluate AEF. VaD patients showed a greatermean latency at M100than controls.There were no significant differences inM100ECD strength and inter-hemispheric positions across diagnosticcategories.there were no significant differences in M100latency,ECD strengthand inter-hemispheric positions between NC group and V-CINDgroup.Correlation analysis showed that there was a correlation between M100latency and scores of MMSE,MoCA,TMT-a,TMT-b,CDT,DST(forwards),DST (backwards) and VFT.Conclusions:1Changes in somatosensory and auditory evoked magnetic fieldcorrelated with cognitive impairment in SIVD patients.2White matter lesions affect somatosensory and auditory tracts in SIVDpatients, while seldom damaging cortical neurons.In our study, the delayedpeak latency and the increased ECD strength in the VaD group support thisidea.3Magnetic field latency measures may provide an objective and sensitiveindex for early dementia detection and monitoring of cognitive function.