本文選題：癲癇　切入點：外周血白細胞端粒長度　出處：《西安醫(yī)學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景癲癇是復(fù)雜的公共衛(wèi)生問題,除癲癇發(fā)作外,認知功能障礙及焦慮抑郁障礙等癲癇神經(jīng)行為共病(neurobehavioral comorbidities of epilepsies,NCE)是加重疾病負擔的主要因素之一。NCE的忽視及治療延誤是癲癇患者病程延長、療效低下、生活質(zhì)量下降及死亡率升高的主要負面因素。外周血白細胞端粒長度(Leukocyte telomere length,LTL)已被證實是癡呆(dementia,DA)、輕度認知功能障礙(mild cognitive impairment,MCI)、重度抑郁癥(Major Depression,MDD)、焦慮等多種疾病的風險預(yù)后標志物。然而目前尚無研究證實NCE患者LTL是否縮短,為此我們探討NCE的影響因素,進一步明確LTL能否成為NCE的潛在生物標志物。方法本研究納入2015年11月至2017年3月就診于西安醫(yī)學(xué)院第一附屬醫(yī)院神經(jīng)內(nèi)科的癲癇患者為病例組(n=42)及性別、年齡、文化程度相匹配的患者家屬為對照組(n=44)。采集所有研究對象的人口統(tǒng)計學(xué)資料及臨床資料,采用蒙特利爾認知評估量表(montreal cognitive assessment,MoCA)、漢密頓焦慮量表(hamilton anxiety scale,HAMA)、漢密頓抑郁量表(hamilton depression scale,HAMD)評價認知功能及焦慮、抑郁水平,并通過實時熒光定量PCR反應(yīng)(real-time quantitative PCR,RT-qPCR)檢測LTL水平。采用單樣本Kolmogorov-Smirnov檢驗、Mann-Whitney檢驗、t檢驗、卡方檢驗、方差分析(ANOVA)、Person相關(guān)分析、Spearman相關(guān)分析、偏相關(guān)分析和多元線性回歸分析進行統(tǒng)計分析。結(jié)果1)癲癇組NCE患病率為57.1%,其中認知功能障礙、焦慮障礙及抑郁障礙的患病率分別為47.6%、38.1%、40.5%,較對照組均明顯升高;2)NCE受多種因素影響,包括社會人口學(xué)因素(受教育程度)、癲癇發(fā)作累積效應(yīng)(病程、新發(fā)/復(fù)發(fā)、發(fā)作頻率、持續(xù)時間)、AEDs暴露后的不良反應(yīng)等;3)已存在共患病的癲癇患者患其他疾病的風險較高。認知功能障礙與焦慮抑郁障礙負相關(guān),焦慮障礙與抑郁障礙正相關(guān)。HAMD總分能夠進入以MoCA和HAMA總分為應(yīng)變量的回歸方程,MoCA總分、HAMA總分能夠進入以HAMD總分為應(yīng)變量的回歸方程。4)癲癇患者LTL明顯縮短,LTL受年齡、受教育程度及癲癇發(fā)作累積效應(yīng)的影響,其中低教育程度、高發(fā)作頻率是LTL縮短的危險因素;5)LTL在伴認知功能障礙、焦慮抑郁障礙的癲癇患者中明顯縮短。偏相關(guān)提示LTL與MoCA總分正相關(guān),與HAMA總分及HAMD總分負相關(guān),LTL能夠進入以MoCA總分、HAMA總分及HAMD總分為應(yīng)變量的回歸方程。結(jié)論NCE現(xiàn)象普遍存在且與社會人口學(xué)因素、臨床特征、AEDs使用情況及共病內(nèi)部等多維度關(guān)聯(lián),而癲癇共患認知障礙及焦慮抑郁障礙三者之間則具有互相促進的雙相關(guān)系。LTL在本研究中的改變能夠反映癲癇及NCE的嚴重程度,并與低受教育程度及高發(fā)作頻率密切關(guān)聯(lián),能夠預(yù)測癲癇共患認知功能障礙及焦慮抑郁障礙的風險,可能成為NCE臨床診斷、治療、評估的潛在生物標志物。
[Abstract]:Background Epilepsy is a complex public health problem, with the exception of seizures, Neurobevioral comorbidities of epilepsia is one of the main factors that aggravate the burden of epilepsy. The neglect of NCE and the delay of treatment are the prolongation of course of disease and the low curative effect of epileptic patients with neurobehavioral syndromes such as cognitive dysfunction and anxiety and depression disorder. The main negative factors of decreased quality of life and increased mortality. Peripheral white blood leukocyte telomere length and telomere length (LTL) have been confirmed to be dementia, mild cognitive impairment, mild cognitive impairment, major depression, anxiety and other diseases. However, there are no studies to confirm whether LTL is shortened in NCE patients. For this reason, we discuss the influence factors of NCE, Methods the study included epileptic patients who were admitted to the Department of Neurology, first affiliated Hospital of Xi'an Medical College from November 2015 to March 2017 as case group (n = 42) and gender, age. The family members of the patients with matched education level were the control group. The demographics and clinical data of all the subjects were collected. The cognitive function, anxiety and depression were evaluated by the Montreal cognitive Assessment scale, the Hamilton anxiety scale, the Hamilton depression scale and the Hamilton depression scale. The level of LTL was detected by real-time quantitative PCR RT-qPCR.The single sample Kolmogorov-Smirnov test was used to detect LTL level by Mann-Whitney test, chi-square test, ANOVA / person correlation analysis and Spearman correlation analysis. Results 1) the prevalence of NCE in epilepsy group was 57.1. The prevalence of cognitive dysfunction, anxiety disorder and depression disorder were 47.6%, 38.1% and 40.5% respectively. Including social demographic factors (educational level, cumulative effect of epileptic seizures (course of disease, new / recurrent, frequency of seizures), There is a higher risk of other diseases in concomitant epilepsy patients. Cognitive dysfunction is negatively correlated with anxiety and depression disorders. There was positive correlation between anxiety disorder and depression. Hamd total score could enter the regression equation with MoCA and HAMA total scores as dependent variables. Hama total score could enter the regression equation with HAMD total score as dependent variable. The influence of education level and epileptic seizure cumulative effect. Low education level and high seizure frequency were the risk factors of LTL shortening in patients with cognitive dysfunction. The partial correlation suggested that LTL was positively correlated with the total score of MoCA. Negative correlation was found with the total score of HAMA and the total score of HAMD. It can enter the regression equation with the total score of Hama and the total score of HAMD as dependent variables. Conclusion the NCE phenomenon exists widely and is associated with social demographic factors, clinical characteristics, usage of AEDs and internal syndromes, and so on. However, there was a mutually reinforcing biphasic relationship between co-epileptic cognitive disorder and anxiety and depression disorder. The changes of LTL in this study could reflect the severity of epilepsy and NCE, and were closely related to low education level and high seizure frequency. It may be a potential biomarker for clinical diagnosis, treatment and evaluation of NCE.
【學(xué)位授予單位】：西安醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R742.1;R749
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本文編號：1649406