| As China is entering aging society, the incidence of cognitive impairment in elderlypeople rises with increasing age and the study of cognitive impairment is being paid greatattention. Cognitive impairment can be classified into mild cognitive impairment (MCI) anddementia in two phases. MCI is the early stage of dementia and associated with anincreased risk for progression to Alzheimer diseases (AD)(10%to15%per year), which is10times that in normal population. Large numbers of scholars at home and abroadcommitted to research the risk factors for cognitive impairment in the elderly. MCI isatteached excessive concern as an early stage of dementia, so it is very important to studythe risk factors in the transformation process of MCI to dementia and cognitive dysfunctionof the patients with MCI. Carotid plaque and stenosis is not only considered as anindependent risk factor of ischemic stroke and cognitive impairment, but also known to bean independent risk factor in the transformation process of MCI to dementia. Therefore,understanding and treatment of carotid artery stenosis at the MCI stage may be an importantstrategy for preventing and delaying the progression to dementia.The most common clinical type of elderly cognitive impairment are AD and vasculardementia (VaD). It is generally accepted previously that the VaD and AD are two types ofdiseases, which have different pathological basis and susceptible gene. But in recent yearsthe role of vascular factors in the pathogenesis of AD is gradually taken seriously. Manyrisk factors associated with vascular factors or hemodynamic can increase the risk of AD.Hypertension, diabetes, hyperlipidemia, current smoking habit, daily alcohol consumptionand Carotid atherosclerosis are considered as common vascular risk factors（VRFs) ofdementia. Carotid atherosclerosis is most popular among elderly people, which can causevascular intimal thickening, carotid plaque, vascular stenosis and occlusion. Carotidatherosclerosis plaque and stenosis often means atherosclerosis of total systemic vascularand encephalic, which maybe the direct causes of cognition decline. AsymptomaticSpontaneous cerebral emboli (SCE) and cerebral hemodynamics low perfusion are associated with an accelerated cognitive and functional decline in asymptomatic patients(>70%stenosis).CEA (carotid endarterectomy) and CAS (carotid artery stenting) have a positive effecton severe carotid artery stenosis, which can improve cerebral perfusion and reducemicro-emboli derived from carotid atherosclerotic plaques and leukodystrophy. However,the effects of CAS on cognitive outcome in patients with carotid artery stenosis arecontroversial. A number of factors may lead to the variation in cognitive responsesobserved in the clinic, including differences in baseline cerebral perfusion status,detrimental effects on procedural emboli, temporary flow interruption and the beneficialeffect of improved cerebral hemodynamics. So a more objective evaluation of short-andlong-term standards, complete and detailed neuropsychological testing, scientificallyrigorous experimental design are required to evaluate the long-term curative effect of CASon the improvement of cognitive function in patients with carotid artery stenosis and MCI.The research about relationship between carotid atherosclerosis and cognitiveimpairment and corresponding treatment of CAS include two parts:(1) To observerelationship between carotid atherosclerotic, smoking, alcohol Intake, and cognitiveimpairment in Chinese elderly people.(2) Using case-control design method and theprospective study, to investigate the effect of CAS on neurocognitive function in patientswith carotid artery stenosis and MCI.Section1Study of the relationship between carotid atherosclerotic and cognitiveimpairment among elderly peopleObjects: the incidence of cognitive impairment is increasing; and its risk factors isattached with great importance. This report focuses on investigating the relationshipbetween carotid atherosclerosis, smoking, alcohol Intake, and cognitive impairment inChinese elderly people.Methods：From January2011to October2012,1367patients aged60years old andover were enrolled from Daping hospital of Chongqing. Screening with high-resolutionB-mode ultrasound,691paitents with carotid atherosclerosis plaque were assigned toplaque group, rest of676cases of plaque-free into the control group. In plaque group,Computerized Tomography angiography (CTA) by a Light Speed VCT64-slice scanner or (DSA)were scheduled to assess the plaque characteristics and carotid artery stenosis.Cognitive function was measured by the Mini-Mental State Examination (MMSE) andActivities of Daily Living (ADL). The χ~2test and logistic regression was used to find therelationship between carotid atherosclerosis, smoking, alcohol intake, and cognitiveimpairment.Results：1.Baseline characterictics in overall patients: In total,803men(58.7％) and564women(41.3%) were registered in this study (mean age of70.4years old),691cases inplaque group（50.5％） and676cases in control group （49.5％）. Of1367patients,116cases had MCI,46cases had dementia. The patients in the two groups did not differ withregard to age, gender, education level and hyperlipidemia. The incidence of hypertension,diabetes mellitus and cardiac disease of plaque group were significantly higher than that ofcontrol group. Meanwhile, the number of current smokers and daily drinking of plaquegroup were much more than control group（p<0.01）. The MMSE score of plaque group（25.9±1.7）were significantly lower than that of the control group（27.1±1.5）（p<0.01）,and patients with MCI（74vs42，p<0.01）,dementia（31vs15，p<0.05）were obvious muchmore than control group.2．Plaque characteristic, degree of stenosis, gender and age distribution in plaquegroup: of691cases in plaque group,406were male（58.8%），285were female（41.2%）.In male patients,147cases（36.2%）had calcified plaque which had the highest percentage,while mixed plaque106（37.2%） were more common in female. Among patients withsevere stenosis,50cases were male（12.3%）,51cases were female（17.9%）, prompting thatfemale had higher rate of severe carotid stenosis than male. From the perspective of agedistribution, mixed plaque had the highest rate in people aged60-69（107cases,37.2%）,while noncalcified plaque was more common in people aged70-79（99cases,38.2%）. Of138patients age above80, calcified plaque had the highest percentage（52cases,37.7%）,among which,23cases with severe stenosis, which means the older the more severestenosis.3. Univariate associations of smoking, drinking, plaque characteristic and stenosis withcognitive impairmentThere was a significant trend for an association of cigarette smoking, alcohol drinking, plaque characteristic and stenosis with cognitive impairment. Current smokers were morelikely to be cognitive impairment (MCI χ~2=6.33，p=0.035),(dementia χ~2=6.16，p=0.042)than past smokers and those who had never smoked. Those who drank every day had ahigher risk for MCI (χ~2=6.52，p=0.023) and dementia（χ~2=6.83，p=0.019）than those whodrank every week, every month and occasional. Patients with mixed plaque andnoncalcified plaque were more likely to be MCI and dementia than patients with calcifiedplaque and control group. Plaque characteristic was associated with MCI（χ~2=7.02，P=0.012） and dementia（χ~2=7.26，P=0.0095）. Patients who with severe carotid stenosishad a higher risk for MCI（χ~2=7.43，P=0.009） and dementia（χ~2=7.87，P=0.0083） thanthose with moderate stenosis and control group. In addition, we found that education level,age and sex were also risk factors for cognitive impairment.4. Multivariate associations of smoking, drinking, plaque characteristic and stenosiswith cognitive impairment: After excluding the risk factors of age, sex, education level,alcohol drinking and carotid plaque, there was still a significant association between currentsmoking with cognitive impairment（MCI RR=2.44,95%CI=1.49-4.08）、（dementiaRR=1.68,95%CI=1.06-2.73） than those who had never smoked and past smokers.Meanwhile, after excluding other risk factors, those who drank every day had asignificantly higher risk of MCI（RR=3.51,95%CI=1.91–6.84）and dementia（RR=3.75,95%CI=1.96-7.05）than occasional drinkers. There was a significant risk in those who drankevery week, MC（IRR=1.63,95%CI=1.07-2.77）、dementia（RR=1.46,95%CI=1.03-2.44）.After excluding other risk factors, there were still a significant association betweencognitive impairment with noncalcified plaque（MCI RR=2.78,95%CI=1.45-6.15）,（dementia RR=2.62,95%CI=1.30-6.02）, mixed plaque （MCI RR=2.96,95%CI=1.56–6.33）,（Dementia RR=2.54,95%CI=1.42-5.99）, and calcified plaque（MCIRR=1.57,95%CI=1.04–2.86）,（Dementia RR=1.31,95%CI=1.10–3.21）compared withcontrol group. While excluding other risk factors, there was a significant association withcognitive impairment and carotid artery stenosis. Compared with those with moderatestenosis（MCI RR=1.59,95%CI=1.02-2.84）、（dementia RR=1.73,95%CI=1.11-3.16）,patients with severe stenosis had higher risk of cognitive impairment（MCI RR=3.72,95%CI=1.88–7.18）、（dementia RR=3.82,95%CI=1.98–7.55）. In addition, after excludingsmoking, drinking, carotid plaque and stenosis, we found an association of cognitive impairment with age, sex and education.Conclusions：1. The incidence of hypertension, diabetes mellitus and cardiac disease of plaquegroup were significantly higher than that of control group. Meanwhile, the number ofcurrent smokers and daily drinking of plaque group were much more than control group.The MMSE score of plaque group were significantly lower than control group, and patientswith MCI and dementia were obvious more than control group.2. In male patients, calcified plaque had the highest percentage, while mixed plaquewere more common in female. Female had higher rate of severe stenosis than male. Fromthe perspective of age distribution, mixed plaque had the highest rate in people aged60-69.while noncalcified plaque was more common in people aged70-79. Of patients age above80, calcified plaque had the highest percentage, who also had the more severe stenosis.3. Current smoking, daily drinking, mixed plaque and noncalcified plaque had asignificant association with cognitive impairment.4. After excluding the risk factors of age, sex and education level, current smoking,daily drinking, carotid plaque characteristic (noncalcified plaque, mixed plaque) and severecarotid stenosis is closely related to MCI and dementia in Chinese elderly people. Whiledrinking every week, calcified plaque and moderate carotid stenosis still have moderatecorrelations with cognitive impairment. Section2Study of carotid artery stenting on cognitive function in elderly people with mildcognitive impairmentObjects：Using case-control design method and prospective study, to investigate theeffect of CAS on neurocognitive function in patients with carotid stenosis and MCI.Methods：A total of240inpatients with carotid stenosis and MCI were consecutively selected from the Department of Neurology, Daping Hospital, Chongqing from January2011to October2011. They were assigned to a treatment group (CAS+drugs therapy,167cases) or a control group (simple drug therapy,73cases) according to patient preference.CAS was performed in the week after the patients were assigned to the treatment group.Patients in the control group were treated with the same oral medication as the treatmentgroup.208patients finished the neuropsychological examinations (NPEs) and CTA,Computerized Tomography Perfusion (CTP) examination before treatment and6months offollow-up.Results:1. Analysis of baseline characteristics:Among the240patients registered in this study,208patients (144in the CAS groupand64in the control group) finished the NPEs and analysis of cognitive scores aftertreatment and6months of follow-up. The pretreatment CTP examinations were performedin155of the218patients and the post-treatment scan in120patients (58%). Technicalsuccess was achieved in all patients in the CAS group. Following stent placement, theseverity of carotid stenosis decreased to21%vs68%preoperatively. The stenosis wasleft-sided in62.5%of patients. In the6month follow-up, we observed stent restenosis in4patients (2.8%), ipsilateral cerebral infarction in3patients (2.1%) and ipsilateral transientischemic attack (TIA) in4patients (2.8%). Of the64patients in the control group,2patients (3.1%) had ipsilateral cerebral infarction and3patients (4.7%) had ipsilateral TIA.The patients in the two groups did not differ with regard to baseline characteristics,educational level, VRFs and NPEs prior to the procedure.2. Neurocognitive and neurologic functions at baseline and6months after in the CASand control groups: In the CAS group, we observed significant improvements in the MMSE(before,24.6±1.7vs after,24.8±1.9; P=0.016), Montreal Cognitive Assessment (MOCA)(before,23.7±1.7vs after,24.1±2.0; P=0.006), Fuld Object Memory Evaluation (FOM)(before,13.8±2.2vs. after,14.0±2.3; P=0.031) and Wechsler Adult IntelligenceScale-digital span (WAIS-DS)(before,6.7±2.1vs. after,6.9±2.3; P=0.040). The change inMOCA was the most significant and rapid verbal retrieval (RVR)(before,25.7±2.1vs.after,25.9±2.3; P=0.201) also exhibited an increasing trend. In comparison, all testparameters were decreased at follow up in the control group, however the reductions were not statistically significant. National Institutes of Health Stroke Scale (NIHSS) and ADLvalues were similar in the two groups at the6month follow-up compared with baselineresults.3. Correlation coefficients between perfusion change and changes in NPE scores: Ofthe84patients in the CAS group who received CTP follow-up,72(86%) demonstratedimprovements in ipsilateral brain perfusion following the procedure; however, noimprovements were identified in the control group. There are close correlations between thechange in perfusion and the change in MMSE (r=0.575) and MOCA (r=0.574), as well asmoderate correlations between the change in perfusion and the change in WIAS-DS(r=0.464), RVR (r=0.449) and FOME (r=0.375).Conclusions：1. Technical success was achieved in all patients in the CAS group. Following stentplacement, the severity of carotid stenosis decreased to21%vs68%preoperatively. In the6month follow-up, we observed stent restenosis in4patients (2.8%), ipsilateral cerebralinfarction in3patients (2.1%) and ipsilateral TIA in4patients (2.8%).Which means CAScan not only remove the patients with carotid artery stenosis, but also safe and effective.2. In the CAS group, we observed significant improvements of NEPs after6monthsthan baseline. In comparison, all test parameters were decreased at follow up in the controlgroup, however the reductions were not statistically significant. Which indicates that CASincreases the neuropsychological tests scores in MCI patients.3. CAS can improve ipsilateral brain perfusion and there were close correlationsbetween the improvements in perfusion and improvements in cognitive score. |
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