外周血白细胞端粒长度与癫痫神经行为共病关系及影响因素研究

发布时间：2018-03-22 16:14

  本文选题：癫痫　切入点：外周血白细胞端粒长度　出处：《西安医学院》2017年硕士论文　论文类型：学位论文

【摘要】：背景癫痫是复杂的公共卫生问题,除癫痫发作外,认知功能障碍及焦虑抑郁障碍等癫痫神经行为共病(neurobehavioral comorbidities of epilepsies,NCE)是加重疾病负担的主要因素之一。NCE的忽视及治疗延误是癫痫患者病程延长、疗效低下、生活质量下降及死亡率升高的主要负面因素。外周血白细胞端粒长度(Leukocyte telomere length,LTL)已被证实是痴呆(dementia,DA)、轻度认知功能障碍(mild cognitive impairment,MCI)、重度抑郁症(Major Depression,MDD)、焦虑等多种疾病的风险预后标志物。然而目前尚无研究证实NCE患者LTL是否缩短,为此我们探讨NCE的影响因素,进一步明确LTL能否成为NCE的潜在生物标志物。方法本研究纳入2015年11月至2017年3月就诊于西安医学院第一附属医院神经内科的癫痫患者为病例组(n=42)及性别、年龄、文化程度相匹配的患者家属为对照组(n=44)。采集所有研究对象的人口统计学资料及临床资料,采用蒙特利尔认知评估量表(montreal cognitive assessment,MoCA)、汉密顿焦虑量表(hamilton anxiety scale,HAMA)、汉密顿抑郁量表(hamilton depression scale,HAMD)评价认知功能及焦虑、抑郁水平,并通过实时荧光定量PCR反应(real-time quantitative PCR,RT-qPCR)检测LTL水平。采用单样本Kolmogorov-Smirnov检验、Mann-Whitney检验、t检验、卡方检验、方差分析(ANOVA)、Person相关分析、Spearman相关分析、偏相关分析和多元线性回归分析进行统计分析。结果1)癫痫组NCE患病率为57.1%,其中认知功能障碍、焦虑障碍及抑郁障碍的患病率分别为47.6%、38.1%、40.5%,较对照组均明显升高;2)NCE受多种因素影响,包括社会人口学因素(受教育程度)、癫痫发作累积效应(病程、新发/复发、发作频率、持续时间)、AEDs暴露后的不良反应等;3)已存在共患病的癫痫患者患其他疾病的风险较高。认知功能障碍与焦虑抑郁障碍负相关,焦虑障碍与抑郁障碍正相关。HAMD总分能够进入以MoCA和HAMA总分为应变量的回归方程,MoCA总分、HAMA总分能够进入以HAMD总分为应变量的回归方程。4)癫痫患者LTL明显缩短,LTL受年龄、受教育程度及癫痫发作累积效应的影响,其中低教育程度、高发作频率是LTL缩短的危险因素;5)LTL在伴认知功能障碍、焦虑抑郁障碍的癫痫患者中明显缩短。偏相关提示LTL与MoCA总分正相关,与HAMA总分及HAMD总分负相关,LTL能够进入以MoCA总分、HAMA总分及HAMD总分为应变量的回归方程。结论NCE现象普遍存在且与社会人口学因素、临床特征、AEDs使用情况及共病内部等多维度关联,而癫痫共患认知障碍及焦虑抑郁障碍三者之间则具有互相促进的双相关系。LTL在本研究中的改变能够反映癫痫及NCE的严重程度,并与低受教育程度及高发作频率密切关联,能够预测癫痫共患认知功能障碍及焦虑抑郁障碍的风险,可能成为NCE临床诊断、治疗、评估的潜在生物标志物。
[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.
【学位授予单位】：西安医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1;R749
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本文编号：1649406