The Cognitive, Neuroimaging And Metabonomics Features Of The Patients With Vascular Cognitive Impairment

Part I The cognitive, clinical and imagingfeatures of the patients with vascular cognitiveimpairmentObjective: By studying the clinical and radiological characteristics of vascularcognitive impairment (VCI) patients, to investigate the clinical and radiological features ofcognitive impairment patients, and look for the features of clinical, psychology and neuralimaging.Methods:49cases of subcortical infarction patients with cognitive impairment wereenrolled as vascular cognitive impairment,42cases without cognitive impairment（Non-vascular cognitive impairment，NVCI）were enrolled continuously. Demographicdata, clinical features, laboratory and imaging studies, history of present illness, pasthistory were collected. A detailed physical examination and the U.S. National Institutes ofHealth stroke Scale ((National Institutes of Health Stroke Scale, NIHSS) score andneuropsychological assessment including Montreal cognitive Assessment (the MontrealCognitive Assessment, MoCA) were assessed, and the neuropsychological scores ofvascular cognitive impairment parents were compared with those42cases of NVCI.Patients with vascular cognitive impairment were matched in gender, age, education withNVCI patients.Results:Risk factors: Hypertension, hyperlipidemia, elevated homocysteine, smoking, alcoholconsumption, atrial fibrillation, syphilis was no significant difference in the VCI group andNVCI group, while the incidence of diabetes of the vascular cognitive impairment patientswas significantly higher than the NVCI group (VCI (38.78%) vs NVCI (16.67%), P=0.02).Clinical features: VCI patients with acute onset (onset time is less than or equal to1week)were28patients (57.12%).The first onset patients were29cases (59.18%),and theincidence of non-first time was20cases (40.82%). Clinical manifestations includedcognitive impairment in memory disorders (32/49,65.31%), the reaction disorders (12/49,24.49%), disorientation (10/49,20.41%), and comprehension disorders (9/49,18.37%). Accompanied by focal signs are mainly central facial paralysis (8/49,16.33%), limbmovement disorder (10/49,20.41%), mild speech impairment (6/49,12.24%). NIHSSscore was (2.10±2.28) points, NIHSS≤3points in37cases (75.51%). NVCI groupslimb movement disorder (30cases,71.43%), mild language dysfunction (23cases,54.76%), central facial paralysis (26cases,61.90%), NIHSS score was (4.05±2.76)points, which is less than3of those23cases, accounting for54.76%. Compared withNVCI, with central facial paralysis, limb movement disorder, the proportion of patientswith mild speech function was lower, and there is statistically significant. Compared withNVCI patients, VCI patients NIHSS score less than3points a larger number of patients,and there is statistically significant.Etiology Analysis: Application stroke TOAST classification, VCI Group arteryatherosclerosis in24cases (48.98%), small vessel occlusion19cases (38.78%),cardiogenic one case (2.04%), three cases of unknown cause (6.12%), other causes twocases (4.08%). NVCI groups: large artery atherosclerosis in22cases (52.38%), smallvessel occlusion in14cases (33.33%), other causes two cases (4.76%), unexplained4cases (9.52%), the two groups of patients with stroke There was no significant differencein type.Neuroimaging features: MRI T2-weighted images with different degrees of white matterdegeneration in37patients (representing75.51%) were assessment by modified Scheltensscores. The results showed a minimum6points, a maximum28points, and an average of15.32±5.87points. NVCI set minimum4points, up10points, an average of6.11±2.11,VCI group score higher than NVCI white matter of patients were treated withnon-parametric Wilcoxon test shows that, P=.0000<0.05, the difference was statisticallysignificant.Vascular assessment: CTA or MRA or cervical ultrasound were completed a total of45cases. Varying degrees of vascular stenosis in37cases were detected, involving101vascular stenosis, based mainly in intracranial vascular lesions, including29middlecerebral arteries for Ethnic Chinese most commonly involving the blood vessels. Theproportion of patients with cerebral vascular stenosis were75.51%in VCI and there wasmore multiple vascular stenosis patients compared with NVCI with statistic significance.Correlation analysis: VCI MoCA scores of patients with cranial MRI T2-weighted imagesdenaturation of Scheltens scores were negatively correlated (Spearman’s rho=-0.495, P <0.05). MoCA Scale subscale scores and correlation of white matter lesions: immediatememory score and white matter lesions negative correlation (rho=-0.577, P <0.05);executive function score and white matter lesions negative correlation (rho=-0.415, P<0.05); Note score and white matter lesions were negatively correlated (Spearman’s rho=-0.382, P <0.05); delayed memory and white matter degeneration negative correlation(Spearman’s rho=-0.389, P <0.05); computing power, orientation, comprehensiondecline scores were not correlated (P>0.05) and white matter lesions.Conclusion: Although subcortical infarction patients with vascular cognitiveimpairment are common, there is still a large proportion subcortical infarction patients isnot associated with cognitive impairment. According to subcortical infarction in patientswithout cognitive impairment group study, we found that it has a different distribution ofrisk factors. VCI patients with diabetes were significantly higher than NVCI patients. VCIcompared with the extent of white matter degeneration in patients with severe NVCI andT2-weighted MRI white matter lesions and cognitive function of the extent of damagecorrelated, especially immediate memory, delayed memory, and executive function. Inthis study, aortic atherosclerosis is the most common cause of VCI, cerebral vascularstenosis patients accounted for75.51%of all patients, intracranial vascular-based, andcompared with NVCI patient, VCI is more common been seen in patients with multipleintracranial arterial stenosis.Part II：Metabolomics studies in patientswith vascular cognitive impairmentObjective: The study of etiology and biological markers VCI has no breakthrough.Because of complex etiology, genomics and proteomics biomarker is very difficult to find.In the first part of the study on the basis of preliminary consideration VCI may occur withglucose metabolism disorders, intracranial atherosclerosis, such as white matterhypoperfusion of the circumstances of the narrow lead, were associated with cellmetabolism. Therefore, metabolomics study were used to compare the difference ofmetabolites in patients with VCI and NVCI, thereby to shed a light for vascularcognitive impairment biomarkers.Methods: Using UHPLC/Q-TOF technology for the serum of patients in healthycontrol group, non-vascular cognitive impairment group, and vascular cognitive impairment group through multivariate statistical analysis methods to analyze thedifferences between the different groups, screen vascular cognitive impairment potentialbiomarkers, and initially explain the mechanism of VCI.Results: There were serum endogenous metabolites significant changes among VCIgroup, NVCI group and HC group.13metabolites were differentially expressed among thethree groups, including the Krebs cycle metabolic pathways (malic acid) and amino acidmetabolism (L-Valine、 L-Glutamine、 Tyrosine fragment、 L-Phenylalanine、2-Phenylacetamide), lipid metabolism (Sphingosine-1-phosphate、Palmitoylcarnitine、Linoelaid ylcarnitine、Elaidic carnitine、tearoylcarnitine、LPAa(0:0/18:2)、PCc(16:0/0:0)、PId(20:4/0:0)), and purine metabolic pathways (such as uric acid) are closely related。Conclusions: Due to the complex etiology, vascular cognitive impairment genomicsand proteomics have certain difficulties. Metabolomics have an advantage in initiallydetecting vascular dementia metabolites, clarifying specifically chemical formula forfurther retrospective proteomics and other biological markers screened studies.