唐榮盛 鄒宏麗 歐愛(ài)春 宋玉強(qiáng)
[摘要] 目的 探討腦小血管?。–SVD)輕度認(rèn)知損害與血清炎性因子相關(guān)性。方法 CSVD病人100例,其中CSVD不伴認(rèn)知障礙者和CSVD伴有認(rèn)知障礙者各50例,同時(shí)選取健康體檢者50例為健康對(duì)照組。采用蒙特利爾認(rèn)知評(píng)估(MoCA)量表及日常生活活動(dòng)能力(ADL)量表評(píng)定CSVD病人認(rèn)知功能,檢測(cè)各組受檢者血清同型半胱氨酸(Hcy)、超敏C反應(yīng)蛋白(hs-CRP)、白細(xì)胞介素6(IL-6)和腫瘤壞死因子α(TNF-α)水平。應(yīng)用Pearson相關(guān)系數(shù)分析血清炎癥因子Hcy、hs-CRP、IL-6和TNF-α水平與CSVD認(rèn)知功能障礙間的相關(guān)性。結(jié)果 CSVD伴認(rèn)知障礙組視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向評(píng)分低于健康對(duì)照組及CSVD不伴認(rèn)知障礙組,差異有顯著性(F=6.782~10.663,P<0.05);健康對(duì)照組、CSVD不伴認(rèn)知障礙組各項(xiàng)目評(píng)分比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。CSVD伴認(rèn)知障礙組炎性因子Hcy、hs-CRP、IL-1、TNF-α水平均明顯高于健康對(duì)照組和CSVD不伴認(rèn)知障礙組,差異有顯著性(F=14.119~20.173,P<0.05);CSVD伴認(rèn)知障礙組血清Hcy、hs-CRP、IL-1、TNF-α水平與MoCA視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向評(píng)分均有相關(guān)性(r=-2.432~-0.039,P<0.05)。結(jié)論 血清學(xué)指標(biāo)Hcy、hs-CRP、IL-1、TNF-α檢測(cè)聯(lián)合MoCA量表和ADL量表評(píng)估可以提高CSVD伴有認(rèn)知功能障礙的診斷效率。
[關(guān)鍵詞] 腦血管障礙;認(rèn)知功能障礙;炎癥趨化因子類(lèi);精神狀態(tài)和癡呆測(cè)試
[中圖分類(lèi)號(hào)] R743.9 ?[文獻(xiàn)標(biāo)志碼] A ?[文章編號(hào)] ?2096-5532(2019)04-0415-04
[ABSTRACT] Objective To investigate the association between mild cognitive impairment and serum inflammatory factors in patients with cerebral small vessel disease (CSVD). ?Methods A total of 100 patients with CSVD were enrolled, among whom 50 had no cognitive impairment and 50 had cognitive impairment, and 50 healthy individuals were enrolled as healthy control group. Montreal Cognitive Assessment (MoCA) and Activity of Daily Life Scale (ADL) were used to evaluate cognitive function in CSVD patients, and the serum levels of homocysteine (Hcy), positive high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. The Pearson correlation coefficient was used to analyze the correlation of the serum inflammatory factors Hcy, hs-CRP, IL-6, and TNF-α with cognitive impairment in CSVD. ?Results Compared with the healthy control group and the non-cognitive impairment CSVD group, the cognitive impairment+CSVD group had significantly lower scores of visual space and executive function, naming, memory, attention, language, abstract ability, and orientation (F=6.782-10.663,P<0.05); there were no significant differences in the scores of each item between the healthy control group and the non-cognitive impairment CSVD group (P>0.05). The cognitive impairment+CSVD group had significantly higher levels of the inflammatory factors Hcy, hs-CRP, IL-6, and TNF-α than the healthy control group and the non-cognitive impairment CSVD group (F=14.119-20.173,P<0.05). In the cognitive impairment+CSVD group, serum levels of Hcy, hs-CRP, IL-6, and TNF-α were correlated with the scores of visual space and executive function, naming, memory, attention, language, abstraction ability, and orientation in MoCA (r=-2.432 to -0.039,P<0.05). ?Conclusion The serological markers Hcy, hs-CRP, IL-6, and TNF-α combined with MoCA and ADL scales can improve the diagnostic efficiency for CSVD with cognitive impairment.
[KEY WORDS] cerebrovascular disease; cognitive dysfunction; chemokines; mental status and dementia tests
腦小血管病(CSVD)是臨床上比較常見(jiàn)的一種腦血管疾病,發(fā)病率較高,其主要的發(fā)病機(jī)制為病人顱內(nèi)小動(dòng)脈、小靜脈與毛細(xì)血管病變導(dǎo)致認(rèn)知功能發(fā)生一定水平的損害[1-3]。目前社會(huì)節(jié)奏比較快,社會(huì)壓力大,老齡化問(wèn)題嚴(yán)峻,CSVD的發(fā)病率和致死、致殘率明顯增高,加重了家庭和社會(huì)的負(fù)擔(dān),降低了病人的生活水平[4-5]。有研究表明,血清同型半胱氨酸(Hcy)與動(dòng)脈粥樣硬化、老年期癡呆(AD)等疾病密切相關(guān),而大多數(shù)CSVD病人均伴有一定程度的AD[6-7]。C反應(yīng)蛋白(CRP)是機(jī)體炎癥反應(yīng)的敏感指標(biāo),其中較為敏感的為血清超敏CRP(hs-CRP),CRP可以作為機(jī)體炎癥的指示因子[8]。白細(xì)胞介素1(IL-1)和腫瘤壞死因子α(TNF-α)也是常見(jiàn)的炎性細(xì)胞因子,可以反映機(jī)體的炎癥水平,與腦神經(jīng)海馬組織壞死、神經(jīng)細(xì)胞凋亡以及小血管炎癥等密切相關(guān)[9-11]。本文研究探討血清炎癥因子Hcy、hs-CRP、IL-1和TNF-α水平[12-15]與CSVD病人認(rèn)知功能障礙間的相關(guān)性,為臨床上CSVD伴有認(rèn)知功能障礙的篩選和治療提供理論依據(jù)。
1 資料與方法
1.1 一般資料
2016年6月—2018年6月,以就診于山東省單縣中心醫(yī)院和青島大學(xué)附屬醫(yī)院神經(jīng)內(nèi)科CSVD病人100例和50例健康志愿者為研究對(duì)象,其中單縣中心醫(yī)院CSVD病人50例,健康志愿者25例;青島大學(xué)附屬醫(yī)院CSVD病人50例,健康志愿者25例。均經(jīng)顱腦磁共振(MRI)檢查診斷明確,平均年齡為(75.32±11.89)歲,平均病程為(7.43±4.33)年。入選標(biāo)準(zhǔn):①無(wú)卒中史和精神系統(tǒng)疾病;②心理檢查和測(cè)試無(wú)障礙,無(wú)神經(jīng)系統(tǒng)癥狀和體征者;③病人及家屬均同意并簽署知情同意書(shū)。排除標(biāo)準(zhǔn):①伴有嚴(yán)重的心肺功能障礙的老年病人;②依從性比較差,溝通困難的病人;③對(duì)試驗(yàn)?zāi)康暮驮囼?yàn)方法不知情并且不配合者。100例CSVD病人中,不伴認(rèn)知障礙組(A組)50例,男24例,女26例;平均年齡為(74.27±15.12)歲;受教育平均時(shí)間(21.4±8.9)年;并發(fā)高血壓15例,高脂血癥15例,糖尿病16例,動(dòng)脈粥樣硬化4例。CSVD伴有認(rèn)知障礙組(B組)50例,男25例,女25例;平均年齡(75.44±19.58)歲;受教育平均時(shí)間(20.7±5.8)年;并發(fā)高血壓17例,高脂血癥12例,糖尿病17例,動(dòng)脈粥樣硬化4例。健康志愿者50例(健康對(duì)照組,C組)中,男21例,女29例;平均年齡(72.31±13.56)歲;受教育平均時(shí)間(19.6±7.2)年;并發(fā)高血壓11例,高脂血癥17例,糖尿病19例,動(dòng)脈粥樣硬化3例。3組受試者一般資料比較,差異無(wú)顯著性(P>0.05)。
1.2 檢測(cè)指標(biāo)和方法
1.2.1 認(rèn)知功能檢測(cè) 采用蒙特利爾認(rèn)知評(píng)估(MoCA)量表[16]和日常生活能力(ADL)量表[17]評(píng)定,MoCA量表包含了視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向7個(gè)項(xiàng)目,總分30分。參照PETERSEN標(biāo)準(zhǔn),無(wú)認(rèn)知功能減退主訴、MoCA評(píng)分≥23分、ADL評(píng)分<22分為認(rèn)知功能正常;MoCA評(píng)分<23分、ADL評(píng)分<22分、認(rèn)知功能損害尚未達(dá)到癡呆標(biāo)準(zhǔn)為伴有認(rèn)知功能障礙[17]。
1.2.2 血清指標(biāo)檢測(cè) 囑受檢者在采血前1 d禁高蛋白、高脂肪飲食,采集清晨空腹靜脈血10 mL,使用同型半胱氨酸測(cè)定試劑盒(Axis-Shield DiagnostiCS Ltd)檢測(cè)血漿Hcy水平,采用超敏C反應(yīng)蛋白檢測(cè)試劑盒(積水醫(yī)療株式會(huì)社)檢測(cè)hs-CRP,ELASA試劑盒檢測(cè)IL-1和TNF-α水平,均按照試劑盒說(shuō)明書(shū)進(jìn)行操作。
1.3 統(tǒng)計(jì)學(xué)分析
采用SPSS 16.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料結(jié)果以±s形式表示,多組數(shù)據(jù)間比較采用單因素方差分析,兩兩比較采用q檢驗(yàn);計(jì)數(shù)資料比較采用卡方檢驗(yàn)或Fisher確切概率法。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié) ?果
2.1 各組MoCA評(píng)分比較
CSVD伴認(rèn)知障礙組視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向評(píng)分低于健康對(duì)照組及CSVD不伴認(rèn)知障礙組,差異有顯著性(F=6.782~10.663,P<0.05);健康對(duì)照組、CSVD不伴認(rèn)知障礙組各項(xiàng)目評(píng)分相比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表1。
2.2 各組血清檢測(cè)指標(biāo)比較
CSVD伴認(rèn)知障礙組炎性因子Hcy、hs-CRP、IL-1、TNF-α水平均明顯高于健康對(duì)照組和CSVD不伴認(rèn)知障礙組,差異有統(tǒng)計(jì)學(xué)意義(F=14.119~20.173,P<0.05);CSVD不伴認(rèn)知障礙組炎性因子Hcy、hs-CRP、IL-1、TNF-α水平均明顯高于健康對(duì)照組,差異均有統(tǒng)計(jì)學(xué)意義(q=3.013~4.876,P<0.05)。見(jiàn)表2。
2.3 CSVD伴認(rèn)知障礙組血清炎性因子指標(biāo)Hcy、hs-CRP、IL-1、TNF-α水平與MoCA評(píng)分的相關(guān)性
CSVD伴認(rèn)知障礙組血清Hcy、hs-CRP、IL-1、TNF-α水平與MoCA視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向評(píng)分均有相關(guān)性(r=-2.432~-0.039,P<0.05)。見(jiàn)表3。
3 討 ?論
隨著現(xiàn)代社會(huì)節(jié)奏的加快,CSVD的發(fā)病率明顯增高,而伴有認(rèn)知功能障礙的CSVD會(huì)嚴(yán)重影響病人的生活質(zhì)量,增加家庭和社會(huì)的經(jīng)濟(jì)負(fù)擔(dān)[18-19]。提高CSVD伴有認(rèn)知功能障礙診斷準(zhǔn)確率,具有重要的意義[20]。本文研究應(yīng)用MoCA量表和ADL量表,參照PETERSEN標(biāo)準(zhǔn),評(píng)定CSVD的認(rèn)知功能,并探討血清炎性因子指標(biāo)Hcy、hs-CRP、IL-1、TNF-α與MoCA評(píng)分的相關(guān)性,旨在從血清學(xué)角度提高CSVD的診斷水平。
既往有研究應(yīng)用腦心通和多奈哌齊聯(lián)合尼莫地平治療CSVD病人的認(rèn)知功能障礙,結(jié)果顯示藥物治療可以提高M(jìn)oCA量表評(píng)分[21-22]。本文研究結(jié)果顯示,CSVD伴有認(rèn)知功能障礙者M(jìn)oCA量表的7項(xiàng)指標(biāo),包括視空間與執(zhí)行功能、命名、記憶、注意力、語(yǔ)言、抽象能力、定向等評(píng)分均較健康對(duì)照組和CSVD不伴認(rèn)知障礙組低,差異有顯著意義。提示MoCA量表評(píng)分與CSVD的認(rèn)知功能有密切的聯(lián)系,可以反映CSVD病人的認(rèn)知功能。有研究應(yīng)用MRI彌散張量成像技術(shù)評(píng)價(jià)CSVD的認(rèn)知功能障礙,力求提高CSVD的診斷效率[23-25]。但是關(guān)于血清學(xué)指標(biāo)與CSVD病人認(rèn)知功能障礙關(guān)系的研究相對(duì)較少。本研究以兩個(gè)醫(yī)院收治的100例CSVD病人和50例健康志愿者為研究對(duì)象,檢測(cè)血清炎性因子Hcy、hs-CRP、IL-1、TNF-α水平與CSVD認(rèn)知功能障礙的關(guān)系,結(jié)果顯示,CSVD伴有認(rèn)知障礙組的炎性因子水平明顯高于其他兩組,CSVD不伴認(rèn)知障礙組炎性因子水平也高于健康對(duì)照組,差異有顯著性。說(shuō)明血清中炎癥指標(biāo)水平與CSVD的發(fā)生有相關(guān)性,可能作為CSVD的診斷指標(biāo)。
另外,既往研究顯示,MoCA量表評(píng)分的降低對(duì)CSVD有提示作用[26-27],血清學(xué)Hcy、hs-CRP、IL-1以及TNF-α水平的升高對(duì)CSVD也有提示作用[28]。為了探討血清炎癥指標(biāo)Hcy、hs-CRP、IL-1、TNF-α水平與MoCA量表評(píng)分的相關(guān)性,本文采用Pearson相關(guān)分析方法進(jìn)行研究,結(jié)果表明,CSVD伴有認(rèn)知障礙組血清Hcy、hs-CRP、IL-1、TNF-α水平與MoCA評(píng)分的7項(xiàng)均存有相關(guān)性。說(shuō)明血清炎癥指標(biāo)Hcy、hs-CRP、IL-1、TNF-α水平檢測(cè)和MoCA量表均可以用于針對(duì)伴有認(rèn)知障礙的CSVD病人的診斷,而且兩者聯(lián)合可以提高診斷的效率,可以在CSVD伴有認(rèn)知功能障礙診斷中發(fā)揮作用。
總之,血清學(xué)指標(biāo)Hcy、hs-CRP、IL-1、TNF-α水平檢測(cè)可以提高CSVD伴有認(rèn)知功能障礙的診斷效率,為臨床CSVD伴有認(rèn)知功能障礙的治療提供新的理論依據(jù)與方法。
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(本文編輯 黃建鄉(xiāng))