| The world's population is ageing, and dementia has to be considered as a public healthpriority. Alzheimer's Association (AA) have reported that the number of people withAlzheimer's disease (AD) in USA in2011is estimated at5.4million and increasing onenew case every68seconds, to11-15million in2050. AD is the sixth leading cause of deathin the United States and the fifth leading cause of death in Americans age≥65years.Although the proportions of deaths due to other major causes of death have decreased in thelast several years, the proportion due to AD has risen significantly, because no effecttreatment available for AD. World Health Organization (WHO) and Alzheimer's DiseaseInternational (ADI) jointly reported that the total number of people with dementiaworldwide in2010is estimated at35.6million and is projected to nearly double every20years, to65.7million in2030and115.4million in2050. The total number of new cases ofdementia each year worldwide is nearly7.7million, implying one new case every fourseconds. Dementia is overwhelming not only for the people who have it, but also for theircaregivers and families. Dementia has been impacting caregivers, families and societiesphysically, psychologically and economically. For the medical researchers, we must do ourbest to make dementia become treatable, thus human would avoid a disaster.Mild cognitive impairment (MCI) was considered as the early stage of dementia whichhas no effective treatments nowadays. More than half of patients with MCI progress todementia within5years. Thus, MCI can be regarded as an increased risk for progression todementia, and its identification could lead to secondary prevention of dementia bycontrolling related somatic factors. Vascular risk factors (VRFs), such as hypertension,diabetes, hyperlipidemia and stroke, play a considerably critical role in the development ofcognitive decline and AD amongst the treatable somatic factors. However, there is still noconsiderable certainty as to whether VRFs are simply an additive element compoundingcognitive decline, or else they play a causal role by exerting direct effects on cognitive impairment. Most epidemiological studies have encountered difficulties in gaging preciselythe role of VRFs severity, and recent research has been focused on identifying practicalparameters which may predict the cognitive impairment precisely. Indeed, chronic cerebralhypoperfusion (CCH) as a result of VRFs is a common vascular component amongcognitive impairment risk factors. Most studies which have investigated the possibility thatCCH may predispose to reduced cognitive function have been focused on carotidsteno-occlusive disease and white matter changes (WMC) for the possibility to find thepractical quantitative predictors of cognitive decline. However, there are few reports whichhave assumed VRFs, carotid stenosis and WMC to be the independent risk factors ofcognitive decline in patient with MCI and then explore correlation between above factorsand cognitive decline.In this prospective study, our aim was to ascertain if VRFs could predict cognitivedecline in an independent elderly cohort with MCI, taking into account carotid stenosis andWMC as two independent risk factors. We also aimed to identify the risk factors promoteconversion from MCI to dementia.Part one Risk factors associated with cognitive decline of the patients with mildcognitive impairmentObjectives: To ascertain if VRFs could predict cognitive decline in an independentelderly cohort with MCI, taking into account carotid stenosis and WMC as two independentrisk factors.Methods: Patients with MCI but no stroke were selected from the inpatients in thedepartment of neurology of Daping Hospital in the city of Chongqing during3rd-9th monthin2008. The patients enrolled into the present study accepted follow-up for3years from2008to2011. The demographic data and VRFs were collected at baseline. The sameneuropsychological tests were administered at entry and at the end of follow-up by aneuropsychologist blinded to the medical record of every subject. All subjects wereexamined by CTA and MRI at entry and at the end of follow-up. We chose MMSE to assesscognitive decline in this study.Results:(1) A total of257subjects with MCI were enrolled into the study at baseline (mean age 70.05years, SD6.78;43.19%women,40.15%subjects with lower education level),246(95.72%) subjects completed the follow-up process, and36subjects had experienced ahistory of stroke during the follow-up. The decrease of MMSE scores≥3appeared in154subjects (62.60%).(2) Comparing the difference between subjects with the decrease of MMSE scores≥3and others,17risk factors had significant differences (p＜0.05), not including educationlevel, oral antihyperglycemic or Insulin, hyperlipidemia and alcohol withdrawal.(3) According to simple regression analysis, the decrease of MMSE scores over the3-year study period was mainly attributed to gender, diabetes mellitus, alcohol consumption,WMC severity and degree of carotid stenosis at baseline and deterioration of WMC severityand carotid stenosis (p＜0.05).(4) The decrease of MMSE scores had to be adjusted for baseline cognitive status aswell as age. Adjusted decrease of MMSE scores as dependent variable and above7riskfactors as independent variables entered in the main regression model (stepwise regression)which indicated that MMSE score decrease was significantly related to diabetes mellitus(p=0.004), baseline WMC severity (p＜0.001), baseline carotid stenosis (p＜0.001) andWMC severity change (p＜0.001). The MMSE score decrease can be described by thefollowing formula: MMSE score decrease=-1.180+1.611(baseline WMCseverity)+5.805(baseline carotid stenosis)+1.221(WMC severity change)+0.957(1if withdiabetes mellitus;0if without)(F=51.583; p＜0.001; R2=0.674).(5) The standardized regression coefficient of above4risk factors can be inaccordance with the order of value as follows: baseline WMC severity (0.570), baselinecarotid stenosis (0.312), WMC severity change (0.244) and diabetes (0.171)。Conclusions:(1) A total of257subjects with MCI were enrolled into the study at baseline(70.05±6.78years),246subjects completed the follow-up process, and36subjects hadexperienced a history of stroke during the follow-up. The decrease of MMSE scores≥3appeared in154subjects (62.60%).(2) The subjects with the characteristics as follows are high-risk groups for cognitivedecline: older men, having hypertension without effective treatment, having diabetes,having hyperlipidemia without use of statins, previous transient ischemic attack and stroke(TIA), smokers, alcohol users, have carotid stenosis and WMC.(3) The MMSE score decrease can be described by the following formula: MMSEscore decrease=-1.180+1.611(baseline WMC severity)+5.805(baseline carotidstenosis)+1.221(WMC severity change)+0.957(1if with diabetes mellitus;0if without).(4) The comparing result of the effect of above risk factors is baseline WMC severity＞baseline carotid stenosis＞WMC severity change＞diabetes.Part two Clinical predictors of conversion from mild cognitive impairment todementiaObjectives: To identify the risk factors promote conversion from MCI to dementia.Methods: Patients with MCI but no stroke were selected from the inpatients in thedepartment of neurology of Daping Hospital in the city of Chongqing during3rd-9th monthin2008. The patients enrolled into the present study accepted follow-up for3years from2008to2011. The demographic data and VRFs were collected at baseline. The sameneuropsychological tests were administered at entry and at the end of follow-up by aneuropsychologist blinded to the medical record of every subject. All subjects wereexamined by CTA and MRI at entry and at the end of follow-up. During the follow-up, thediagnosis of dementia should be noted immediately.Results:(1) A total of257subjects with MCI were enrolled into the study at baseline,246(95.72%) subjects completed the follow-up process. Considering the cognitive diagnosisperformed at the last clinical visit, dementia was diagnosed in86(34.96%) subjects (amongthose who progressed to dementia,60.47%progressed to AD,30.23%to VaD and9.30%toMD). MMSE score decrease in subjects diagnosed as MD (9.00±1.69) was larger than VaD(5.92±2.45), and the smallest in subjects diagnosed as AD (5.58±1.98).(2) We compared the patients diagnosed with dementia at last visit and non-dementiapatients and got a result that age, educational level, hypertension, diabetes, stroke duringfollow-up, baseline carotid stenosis, baseline WMC severity, carotid stenosis change andWMC severity change were significantly different between the two groups of patients (p＜0.05).(3) Using Cox proportional hazards model to analyze86dementia patients, we foundthat diabetes, baseline WMC severity (severe), baseline carotid stenosis (moderate to severe) and carotid stenosis change during follow-up have played significant role in conversionfrom MCI to dementia (p＜0.05).(4) Using Cox proportional hazards model to analyze52AD patients, we found thatdiabetes, baseline WMC severity (severe), baseline carotid stenosis (moderate to severe)have played significant role in conversion from MCI to AD (p＜0.05).(5) Using Cox proportional hazards model to analyze26VaD patients, we found thatmale, hypertension, hyperlipidemia and baseline WMC severity (severe) have playedsignificant role in conversion from MCI to VaD (p＜0.05).Conclusions:(1) The conversion rate from MCI to dementia was11.65%per year, and theconversion rate from MCI to AD was7.05%per year.(2) The subjects with the characteristics as follows are high-risk groups for convertingto dementia: older men, high educational level, having hypertension, having diabetes,stroke, have carotid stenosis and WMC.(3) The clinical predictors of conversion from MCI to dementia were diabetes, severeWMC, moderate to severe carotid stenosis and aggravating carotid stenosis.(4) The clinical predictors of conversion from MCI to AD were diabetes, severe WMC,moderate to severe carotid stenosis.(5) The clinical predictors of conversion from MCI to VaD were male, hypertension,hyperlipidemia and baseline severe WMC.
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