| BackgroundThis study was supported by funding from the Science and Technology Development Program of Shandong Province(No.2014GSF118106),and the Science and Technology Development Program of Liaocheng(No.2014GJH21),and the "Twelfth Five Year" National Science and technology program of the Ministry of Science and Technology of China(No.2011BAI08B02).Featured with high morbidity and mortality,stroke has caused serious damage to people’s health both in developed countries and developing countries.In European and American,about four-fifths stroke patients are ischemic stroke and about half of those patients are accompanied with ipsilateral extracranial carotid artery stenosis.Although in china,intracranial arterial stenosis is accompanied with stroke more frequently,patients with ipsilateral extracranial carotid artery stenosis are still account for approximately 33.3%.With the rapid progress of imageology and neuropathology,research about carotid atherosclerosis and relevent researches,such as cerebral white matter degeneration,cognitive disorder and Lacunar Infarct(LI),constantly go deeper.The collateral circulation of cerebral white matter is insufficient,as it is located in a border area of three vascular blood supplies:the anterior,middle,and posterior cerebral artery.Cerebral white matter degeneration is one of the most common brain damage for old people,which usually implies brain ischemia and abnormal metabolism,and LA is related to the occurrence and development of cognition impairment.The typical radiographic characteristic of cerebral white matter degeneration is the status of leukoaraiosis with hyperintensity on T2/FLAIR in MRI.The main pathologic changes are diffuse demyelination,glial proliferation and axonal degeneration of periventricular and deep white matter tract,with the association fibers and projection fibers being involved.The pathologic changes mostly happen in the periventricular area,and the nearer to the subcortex,the smaller of the lesion volume and incidence are.Carotid artery stenosis-induced chronic brain ischemia is one of the main causes of cerebral white matter degeneration.Cerebral white matter degeneration is demonstrated to be the main mechanism of cognitive disorder.Vascular cognitive impairment(VCI)is considered to be the only preventable and treatable cognitive disorder so far.VCI patients could often have several cognitive damages,including speech,calculation,judgment,memory,visuospatial skills,etc,which induces abnormalities of behaviors,feelings and traits,and could eventually lower abilities of daily living and work.Hypertension,diabetes and smoking contribute to the risk factors of VCI,and are strongly related to carotid artery stenosis.Meanwhile,in clinic,carotid artery stenosis is regularly found to be accompanied with cognitive disorder.Therefore,the correlation between them becomes the hotspot of research.Carotid artery stenosis may lead to cognitive disorder or further intracranial atherosclerosis directly.Carotidendarterectomy(CEA)is the first choice of patients with severe carotid artery stenosis.However,anesthesia tolerance,surgical approach and long time blood supply blocking make CEA performing more difficult and limite its application and promotion.Carotid artery stenting(CAS)is another approach used to improve cerebral blood flow and prevent recurrence of stroke.Considering the advantage of less trauma,local anesthesia,only several seconds of blood supply blocking and rapid recovery after operation,CAS has become one of the main therapy methods for severe carotid artery stenosis.Since carotid artery stenosis could induce cerebral white matter degeneration and result in cognitive disorder,we hypothesized that CAS could improve the cognitive function of patients with carotid artery stenosis-induced lacunar infarction(LI)or cerebral white matter degeneration.LI is intracranial deep perforating artery stenosis or occlusion-induced focus cerebral ischemic necrosis,accounting for about 1/4 of all ischemic stroke.LI was originally considered to be caused by small vessel disease,whereas,recent studies manifested that LI was strongly related to carotid artery stenosis and cerebral white matter degeneration,and the carotid artery stenosis increased the risk of cognitive disorder and dementia.To the best of our knowledge,whether CAS could improve the cognitive disorder of patients with carotid artery stenosis-induced lacunar infarction(LI)or cerebral white matter degeneration is unreported.Our study is designed to solve this problem.ObjectiveCAS is one of the main treatments for patients with carotid artery stenosis.However the influence of CAS upon the cognitive function in patients with LI and cerebral white matter degeneration remains unclear.The aim of our study is to explore the cognitive changes and analyze related risk factors in patients with LI,carotid artery stenosis and cerebral white matter degeneration.MethodsThis study was a multicenter prospective cohort study.The treatment group patients were from the inpatients of neurology department in Liaocheng people’s Hospital,Shandong Provincial Hospital,Nanjing General Hospital and the Third People’s Hospital in Liaocheng(all the four hospitals are sub-centers of China Interventional Stroke Registry),and all the patients were with severe carotid artery stenosis,LI,cerebral white matter degeneration and underwent CAS.The control group patients were the middle-aged and aged people who accepted health check in central neurology clinic during the same period.Montreal Cognitive Assessment(MoCA),mini-mental state examination(MMSE),clinical dementia rating(CDR)and Wechsler Adult Intelligence Scale-Rivised by China(WAIS-RC)were conducted in 579 patients with LI and cerebral white matter degeneration before CAS and 1 month,6 months,1 year,2 years and 3 years after CAS and the scores were compared with those of 552 healthy persons in the control group.Logistic regression analysis also was conducted for the potential risk factors of cognitive function.All the neuropsychological tests were performed by skilled associate chief neurologists.Results(1)Total 628 patients,aged between 49 to 73,and with LI,cerebral white matter degeneration,carotid artery stenosis and underwent CAS were selected into the treatment group.Among them,21 cases had completely occluded carotid revascularization.29 cases developed complications in the perioperative period(4.6%),thereinto,8 cases with severe vasospasm,10 cases with transient cardiac arrest during balloon pre-dilation,5 cases with arterial dissection and disappeared after stenting,3 cases with intracranial hyperperfusion,1 case with ipsi lateral ophthalmic artery embolization,1 case with the formation of arteriovenous and hematoma fistula in artery puncture place and 1 case with a little blood extravasation of section C1 of internal carotid artery and spontaneous remising soon.After active treatment,2 cases died and one case maimed(NIHSS score 8 points)in 3 cases with intracranial hyperperfusion.1 case with ipsilateral ophthalmic artery embolization went blind.Symptoms of neurological deficit did not arise in the other patients.There were 4 death during the follow-up,thereinto,2 cases died of sudden cardiac death 7 months and 19 months after operation,1 case died of cerebral hemorrhage 21 months after operation and 1 case died of traffic accident 25 months after operation.A total of 49 patients were excluded for death,losing follow-up and incompleting the full assessment of cognitive,therefore 579 patients were enrolled to analysis eventually.579 healthy people aged from 48 to 73 were enrolled to the control group.The potential risk factors of atherosclerosis in the two groups were well-matched.Compared with the control group,cerebral blood flow(CBF)in the treatment group was significant lower.The difference was statistically significant(P<0.001).(2)Compared with the control group,the scores of MoCA,MMSE and partial cognitive domain score(Alternate Connection Test,Cube Copy Test,Clock Drawing Test,concentration Delay Recall Test)in the treatment group were significant lower before opeartion,1 month and 6 months after opeartion(P<0.05 or 0.01 respectively).However,6 months,1 year,2 years and 3 years after operation,the scores of MoCA,MMSE and partial cognitive domain were significantly improved than preoperation in the treatment group.The differences were statistically significant(P<0.05 or 0.01).(3)In the treatment group,all the scores of CDR were greater than or equal to 0.5 before operation.Nobody scored of 0.The CDR scores of 11 patients decreased to 0 one month after CAS,and this change was particularly evident 6 months after CAS.The CDR scores of 56 patients decreased to 0 three years after CAS.The number of patients with a 0.5 score of CDR was also increasing with postoperative time-extension,and increased to 411 cases(about 71.0%)3 years after CAS.Meanwhile,the number of patients with 1 or higher score of CDR was significantly decreased,from 164 and 114 to 80 and 32 respectively,with the decreasing amplitudes of 51.2%and 71.9%respectively.(4)Compared with the control group,the WAIS-RC(Full Scale IQ,Performance IQ and Verbal IQ Test)scores of the treatment group were significant lower.The difference was statistically significant(P<0.01).Compared with before CAS,the WAIS-RC scores in the treatment group rapidly improved,especially 6 months after CAS.The difference was statistically significant(P<0.01).With postoperative time-extension,the WAIS-RC scores in the treatment group were further improved,and part cognitive domains(such as verbal comprehension,awareness,vocabulary,similarities and information,etc.)were improved significantly.Even compared with the control group,the difference wasn’t statistically significant(P>0.05).(5)Logistic regression analysis was conducted gradually with MoCA scores as dependent variable in the treatment group followed up for 3 years after operation and with the age,hypertension,smoking,diabetes,coronary heart disease,alcoholconsumption,total cholesterol,triglycerides,educational level and CAS as independent variable.The statististical results showed that the MoCA scores has obvious correation with lower educational level(OR=2.877,95%CI 1.113～7.436;P=0.033),age(OR=5.038,95%CI 1.687-15.045;P=0.009),diabetes(OR=2.489,95%CI 1.058～5.855;P=0.046)and hypertension(OR=1.549,95%CI 1.144～2.097;P=0.021),but has no correation with smoking,total cholesterol,alcohol consumption,triglycerides and coronary heart disease.CAS(OR=2.321,95%CI 0.796～6.767;P=0.075)was not the independent protective factor.ConclusionCognitive dysfunction was more severe in the patients with severe carotid artery stenosis,LI and cerebral white matter degeneration.CAS could improve these cognitive function,andmaintain and raise a long-period(3 years)therapeutic effect continuously.The decrease of cognitive function may relate with age over 65,being accompanied with hypertension or diabetes and lower education level,but CAS was not its independent protective factor. |
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