本文選題：路易體病 + 帕金森病�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文

【摘要】：研究背景路易體病(Lewy body disease,LBD)是一種常見(jiàn)的神經(jīng)退行性疾病,以路易小體(Lewy body,LB)在神經(jīng)元胞體和軸突內(nèi)的沉積為主要病理表現(xiàn)。帕金森病(Parkinson disease,PD)是最常見(jiàn)的LBD,病理表現(xiàn)為黑質(zhì)神經(jīng)元的丟失以及以α-synuclein為主要成分的LB沉積。該病臨床早期以靜止性震顫、運(yùn)動(dòng)遲緩等運(yùn)動(dòng)系統(tǒng)表現(xiàn)為主,晚期可出現(xiàn)認(rèn)知障礙等非運(yùn)動(dòng)系統(tǒng)癥狀。ApoE ε4以及合并AD病理改變可能與PD出現(xiàn)認(rèn)知損傷相關(guān)。在國(guó)內(nèi)尚缺乏基于人腦組織庫(kù)的對(duì)PD以及PD認(rèn)知損害的臨床病理研究。研究目的本研究旨在探究路易體相關(guān)病理改變(Lewy-related pathology,LRP)在中國(guó)捐獻(xiàn)人腦組織中的分布情況,進(jìn)一步探究PD及PD相關(guān)認(rèn)知損傷的臨床病理聯(lián)系。研究方法本研究共納入中國(guó)醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院人腦組織庫(kù)中76例具有臨床信息、ECog認(rèn)知評(píng)分、ABC評(píng)分的捐獻(xiàn)者人腦組織,進(jìn)一步進(jìn)行α-synuclein染色以及ApoE基因分型。針對(duì)α-synuclein染色陽(yáng)性的病例,按照Braak LRP分期標(biāo)準(zhǔn)對(duì)染色結(jié)果進(jìn)行分期,并利用描述統(tǒng)計(jì)以及秩和檢驗(yàn)分析PD和PD認(rèn)知損害的臨床病理關(guān)系。研究結(jié)果在本研究中,根據(jù)捐獻(xiàn)者家屬提供的臨床病史,PD診斷敏感度為66.7%,特異度為98.6%;假陽(yáng)性率為33.3%,假陰性率為1.4%。LB分期可能與臨床認(rèn)知損害相關(guān)。隨著B(niǎo)raak分期的升高,ECog總分及ECog各項(xiàng)評(píng)分呈上升趨勢(shì)(ECog總分:p = 0.091;記憶力:p = 0.079;語(yǔ)言:p= 0.068;視空間:p = 0.060;計(jì)劃:p=0.255;組織:= 0.064;注意力:= 0.129)。PD患者伴認(rèn)知損傷較為常見(jiàn),LB合并AD病理改變可能共同促進(jìn)認(rèn)知損害,且ApoE ε4攜帶者可能更容易發(fā)生認(rèn)知損傷。研究結(jié)論根據(jù)目前的臨床診斷標(biāo)準(zhǔn),對(duì)PD及PD認(rèn)知損傷的認(rèn)識(shí)可能存在不足。PD認(rèn)知損傷可能與LB合并AD病理改變相關(guān),且ApoE ε4攜帶者可能更加具有認(rèn)知損傷的易感性。
[Abstract]:Background Lewy body disease (LBD) is a common neurodegenerative disease characterized by the deposition of Lewy body LB in neuronal bodies and axons. Parkinson disease (PD) is the most common type of LBD.It is characterized by the loss of neurons in the substantia nigra and the LB deposition of 偽 -synuclein. The early clinical manifestations of the disease were quiescent tremor, motor retardation and other motor system manifestations. The non-motor system symptoms such as cognitive impairment. ApoE 蔚 4 and the pathological changes associated with AD may be associated with cognitive impairment in PD. There is a lack of clinical and pathological studies on PD and PD cognitive impairment based on human brain tissue bank in China. Objective to investigate the distribution of Lewy-related pathological changes (LRP) in Chinese human brain and to explore the clinicopathological relationship between PD and PD related cognitive impairment. Methods 76 donors with clinical information ECog cognitive score and ABC score were included in the human brain tissue bank of Peking Union Medical College, Chinese Academy of Medical Sciences, and further 偽 -synuclein staining and ApoE genotyping were performed. The results of 偽 -synuclein staining were classified according to Braak LRP staging criteria, and the clinicopathological relationship between PD and PD cognitive impairment was analyzed by descriptive statistics and rank sum test. Results in this study, the sensitivity, specificity, false positive rate and false negative rate of PD diagnosis were 66.7 and 98.6, respectively, and the false negative rate of 1.4g / LB stage might be related to clinical cognitive impairment in this study, according to the clinical history provided by donor's family, the sensitivity of PD was 66.7, the specificity was 98.6, the false positive rate was 33.3 and the false negative rate was 1.4. With the increase of Braak stage, the total score of ECog and the scores of ECog showed an upward trend (ECog total score:% p = 0.091; memory: P = 0.079; language: p = 0.068; Visual space: p = 0.060; Planning: p0.255; organizational: 0.064; attention: 0.129) .PD patients with cognitive impairment are more common with LB combination. The pathological changes of AD may contribute to cognitive impairment, Moreover, ApoE 蔚 4 carriers may be more prone to cognitive impairment. Conclusion according to the current clinical diagnostic criteria, PD and PD cognitive impairment may be deficient. PD cognitive impairment may be associated with LB with AD pathological changes, and ApoE 蔚 4 carriers may be more susceptible to cognitive impairment.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R742.5

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