胡方方 張尊勝 楊新新
·綜述·
腦白質(zhì)高信號與帕金森病認(rèn)知功能障礙研究進(jìn)展
胡方方 張尊勝 楊新新
帕金森病是中老年人群常見的神經(jīng)變性病,認(rèn)知功能障礙是其最常見的非運(yùn)動癥狀,嚴(yán)重影響患者生活質(zhì)量。認(rèn)知功能障礙與多種因素有關(guān),如腦白質(zhì)高信號,且腦白質(zhì)高信號是帕金森病認(rèn)知功能障礙的重要病理改變。本文從神經(jīng)元通路、腦白質(zhì)體積變化和擴(kuò)散張量成像方面闡述腦白質(zhì)高信號與帕金森病認(rèn)知功能障礙之間的關(guān)系,為早期診斷帕金森病提供新的方向。
帕金森??; 認(rèn)知障礙; 磁共振成像; 綜述
帕金森?。≒D)是中老年人群常見的神經(jīng)變性病,主要病理學(xué)特征為黑質(zhì)多巴胺能神經(jīng)元缺失和路易小體(LB)形成,臨床癥狀除運(yùn)動遲緩、肌強(qiáng)直、靜止性震顫和姿勢步態(tài)異常等運(yùn)動癥狀外,常伴認(rèn)知功能障礙、睡眠障礙、抑郁和自主神經(jīng)功能障礙等非運(yùn)動癥狀(NMS)[1-3],其中,認(rèn)知功能障礙臨床最為常見,表現(xiàn)為輕度認(rèn)知損害(MCI)和帕金森病癡呆(PDD)[4],且程度隨疾病進(jìn)展而逐漸加重,嚴(yán)重影響患者生活質(zhì)量。研究顯示,有30%~35%的早期帕金森病患者存在認(rèn)知功能障礙,其中20%為輕度認(rèn)知損害[2-3,5-7]。帕金森病認(rèn)知功能障礙與多種因素相關(guān),如發(fā)病年齡、病情嚴(yán)重程度和體位性低血壓等[6]。帕金森病認(rèn)知功能障礙可繼發(fā)于多種途徑,如腦組織路易小體增多、多巴胺能和非多巴胺能神經(jīng)遞質(zhì)系統(tǒng)功能障礙、顱內(nèi)血管病變、腦白質(zhì)高信號(WMH)、腦容積改變和灰質(zhì)萎縮[8-9]。腦白質(zhì)高信號作為帕金森病認(rèn)知功能障礙的重要病理改變,逐漸受到臨床關(guān)注[10-11]。流行病學(xué)研究顯示,腦白質(zhì)高信號在正常老年人群中發(fā)生率為30%~55%,帕金森病患者腦白質(zhì)高信號發(fā)生率高于正常老年人群[12]。此外,帕金森病癡呆又可使帕金森病進(jìn)展加速和病殘率升高,因此,對帕金森病認(rèn)知功能障礙的早期診斷和早期干預(yù)尤為重要。本文擬就腦白質(zhì)高信號與帕金森病認(rèn)知功能障礙的研究進(jìn)展進(jìn)行綜述。
腦白質(zhì)高信號在MRI上表現(xiàn)包括兩種類型,即深部白質(zhì)高信號(DWMH)和腦室周圍白質(zhì)高信號(PWMH),前者主要發(fā)生于皮質(zhì)下,影響皮質(zhì)下短纖維;后者與腦深部小血管毗鄰,影響皮質(zhì)間聯(lián)系纖維[13-14]。深部白質(zhì)高信號和腦室周圍白質(zhì)高信號病理改變不同,前者提示腦缺血;后者提示慢性腦供血不足,但無明顯缺血證據(jù)。盡管二者均與執(zhí)行功能相關(guān),但是由于解剖學(xué)部位和病理學(xué)特點(diǎn)不同,其對認(rèn)知功能障礙的影響也不盡相同,深部白質(zhì)高信號與輕度認(rèn)知損害密切相關(guān),腦室周圍白質(zhì)高信號與認(rèn)知功能障礙進(jìn)展速度相關(guān)[14]。Mak 等[13]研究顯示,帕金森病認(rèn)知功能障礙與腦室周圍白質(zhì)高信號相關(guān),而與深部白質(zhì)高信號無明顯關(guān)聯(lián)性,究其原因,可能是由于深部白質(zhì)高信號僅影響皮質(zhì)-皮質(zhì)間短的弓形“U”纖維,這種“U”纖維在近皮質(zhì)區(qū)較為密集。
1.腦白質(zhì)體積與帕金森病認(rèn)知功能障礙 帕金森病認(rèn)知功能障礙包括輕度認(rèn)知損害和帕金森病癡呆,輕度認(rèn)知損害被認(rèn)為是進(jìn)展至癡呆的過渡階段,研究顯示,約50%的輕度認(rèn)知損害最終進(jìn)展為癡呆[15-16],因此,早期診斷輕度認(rèn)知損害有助于阻止其向癡呆進(jìn)展。目前研究主要集中于灰質(zhì)病變,特別是前額葉皮質(zhì)病變參與帕金森病認(rèn)知功能障礙。近年研究顯示,白質(zhì)萎縮特別是額頂區(qū)萎縮可能參與帕金森病認(rèn)知功能障礙,涉及執(zhí)行功能、記憶力和言語功能。Wen等[17]對42例帕金森病患者進(jìn)行為期18個月的隨訪,結(jié)果顯示,12例出現(xiàn)輕度認(rèn)知損害,頭部MRI可見前額葉體積縮小,與Lee等[18]的擴(kuò)散張量成像(DTI)研究結(jié)果相一致:與認(rèn)知功能正常的帕金森病患者和無進(jìn)展的帕金森病輕度認(rèn)知損害患者相比,進(jìn)展為帕金森病癡呆的患者前額葉體積縮小,推測前額葉體積縮小可能與軸突損害有關(guān);他們還發(fā)現(xiàn),帕金森病輕度認(rèn)知損害與額葉功能相關(guān),包括注意力、工作記憶和執(zhí)行功能等。更有意義的是,該項(xiàng)研究還顯示,低于基線水平的額葉體積是預(yù)測帕金森病輕度認(rèn)知損害的重要影像學(xué)指標(biāo)。腦白質(zhì)高信號導(dǎo)致帕金森病認(rèn)知功能障礙的原因有多種,目前尚未完全闡明。動物實(shí)驗(yàn)顯示,腦缺血導(dǎo)致α-突觸核蛋白(α-Syn)寡聚化,加重帕金森病患者腦組織病理改變[19];此外,腦缺血加重已存在的細(xì)胞微觀結(jié)構(gòu)破壞[10],導(dǎo)致前額葉皮質(zhì)下神經(jīng)環(huán)路損害而發(fā)生認(rèn)知功能障礙。
2.腦白質(zhì)膽堿能通路與帕金森病認(rèn)知功能障礙 腦白質(zhì)高信號除通過影響α-Syn代謝而致帕金森病認(rèn)知功能障礙外,還可以影響腦白質(zhì)膽堿能通路[6,20-21]。近年研究側(cè)重于采用膽堿能通路高信號評分(CHIPS)特異性評價(jià)腦白質(zhì)中膽堿能纖維損害程度,而非簡單針對腦白質(zhì)損害程度進(jìn)行主觀評價(jià)或?qū)δX白質(zhì)體積進(jìn)行測量,從而更準(zhǔn)確、客觀地評價(jià)帕金森病患者認(rèn)知功能。Park等[22]研究顯示,帕金森病癡呆患者CHIPS評分與認(rèn)知功能障礙程度呈正相關(guān),CHIPS評分越高、進(jìn)展為癡呆的可能性越大;此外,該項(xiàng)研究還發(fā)現(xiàn),帕金森病、路易體癡呆(LBD)和阿爾茨海默?。ˋD)患者的膽堿能通路受損機(jī)制相似,認(rèn)知功能障礙尤其是言語障礙與腦白質(zhì)高信號密切相關(guān)。腦白質(zhì)高信號導(dǎo)致癡呆的原因,考慮可能與路易小體形成有關(guān),但β-淀粉樣蛋白(Aβ)的作用亦不容忽視[23],這是由于腦白質(zhì)高信號可以引起Aβ清除障礙[24]。腦白質(zhì)高信號對帕金森病和路易體癡呆的作用機(jī)制較阿爾茨海默病復(fù)雜;膽堿能通路損害對帕金森病的影響程度較阿爾茨海默病嚴(yán)重,尤其在疾病早期階段[25]。上述基于CHIPS評分的研究結(jié)果表明,無論何種類型的癡呆,膽堿能通路均受到損害,此為膽堿酯酶抑制劑對阿爾茨海默病、路易體癡呆和帕金森病癡呆均有效的原因[26]。推測腦白質(zhì)高信號影響帕金森病認(rèn)知功能障礙的可能機(jī)制為腦白質(zhì)高信號破壞皮質(zhì)與皮質(zhì)間或額葉皮質(zhì)下神經(jīng)網(wǎng)絡(luò),阻斷走行于扣帶回內(nèi)側(cè)和外囊外側(cè)的膽堿能纖維。
3.腦白質(zhì)高信號通過影響皮質(zhì)功能參與帕金森病認(rèn)知功能障礙 腦白質(zhì)高信號不僅影響神經(jīng)遞質(zhì)傳遞,而且影響灰質(zhì)功能[27]。Ham等[14]的研究顯示,帕金森病認(rèn)知功能障礙患者皮質(zhì)變薄,表現(xiàn)為深部白質(zhì)高信號的帕金森病患者皮質(zhì)受累范圍更為廣泛,包括整個額葉、部分顳頂葉;表現(xiàn)為腦室周圍白質(zhì)高信號的帕金森病患者僅部分額葉受累。多元線性回歸分析顯示,深部白質(zhì)高信號相關(guān)皮質(zhì)變薄與額葉癡呆具有相關(guān)性,而腦室周圍白質(zhì)高信號相關(guān)皮質(zhì)變薄與額葉癡呆無明顯關(guān)聯(lián)性[14]。腦白質(zhì)高信號導(dǎo)致皮質(zhì)改變的原因可能存在以下幾方面:(1)腦白質(zhì)高信號是神經(jīng)元缺失所致,即皮質(zhì)變薄繼發(fā)于腦白質(zhì)高信號。(2)腦白質(zhì)高信號是皮質(zhì)病變的反映,即腦白質(zhì)高信號繼發(fā)于皮質(zhì)病變。(3)腦白質(zhì)高信號與皮質(zhì)病變具有相同的病理生理學(xué)過程,可能繼發(fā)于腦缺血。此外,亦有臨床研究顯示,帕金森病患者認(rèn)知功能障礙與皮質(zhì)厚度具有相關(guān)性[14]。
大多數(shù)帕金森病影像學(xué)研究探討帕金森病認(rèn)知功能障礙相關(guān)腦區(qū)改變,主要集中于灰質(zhì)萎縮研究,較少探討白質(zhì)完整性在帕金森病認(rèn)知功能障礙中的作用。DTI可以拓寬我們對腦白質(zhì)高信號參與帕金森病認(rèn)知功能障礙的理解[28]。
1.DTI特點(diǎn) DTI已經(jīng)成為近年帕金森病影像學(xué)研究熱點(diǎn)。DTI是一種探測腦組織內(nèi)微觀結(jié)構(gòu)水分子擴(kuò)散運(yùn)動的定量MRI技術(shù),對白質(zhì)纖維束尤為敏感[29-31],包括2項(xiàng)主要參數(shù),即部分各向異性(FA)和平均擴(kuò)散率(MD),用于測量白質(zhì)完整性,其中,F(xiàn)A值評價(jià)水分子擴(kuò)散時各向異性程度或水分子定向擴(kuò)散過程,反映白質(zhì)纖維束的連貫性,F(xiàn)A值越高、水分子沿一個軸方向的擴(kuò)散越明顯;MD值評價(jià)水分子擴(kuò)散速度,MD值升高表明水分子擴(kuò)散受到微觀結(jié)構(gòu)屏障物的限制(如細(xì)胞膜和大分子物質(zhì))、MD值降低表明水分子擴(kuò)散未受到限制[29-34]。白質(zhì)纖維束FA值主要由神經(jīng)絲和微管的細(xì)胞骨架及軸突膜決定。腦組織FA值異常在病理學(xué)上表現(xiàn)為神經(jīng)元或神經(jīng)膠質(zhì)細(xì)胞缺失、神經(jīng)膠質(zhì)增生或脫髓鞘、白質(zhì)完整性破壞[10]。
2.DTI顯示腦白質(zhì)高信號與帕金森病認(rèn)知功能障礙的關(guān)系 DTI研究顯示,帕金森病癡呆患者部分腦區(qū)(如扣帶回、胼胝體、額葉、顳葉和枕葉)白質(zhì)破 壞 明顯[10,35-36],即 上 述腦 區(qū) FA 值降 低[28]。Kamagata等[29]的研究顯示,與正常對照組相比,無癡呆的帕金森病患者腦白質(zhì)FA值和MD值無明顯變化,帕金森病癡呆患者白質(zhì)纖維束FA值降低、MD值升高,上述受影響的白質(zhì)纖維束包括扣帶回、胼胝體膝部、下額枕部纖維束、上縱束和下縱束,且均為雙側(cè)受損,與Hattori等[10]的研究結(jié)果一致。腦白質(zhì)高信號可見于多種疾病,帕金森病患者腦白質(zhì)存在路易小體異常,如路易神經(jīng)突和路易軸突異常,這種路易小體異常的積累可能改變軸突結(jié)構(gòu),導(dǎo)致主要白質(zhì)纖維束FA值降低[37-38]。路易小體異常是導(dǎo)致帕金森病患者認(rèn)知功能障礙的另一原因。認(rèn)知功能包括執(zhí)行功能、記憶力、言語功能和視空間能力等,故帕金森病患者認(rèn)知功能障礙表現(xiàn)各異,存在執(zhí)行功能障礙和言語障礙的帕金森病患者前額葉FA值降低,存在記憶功能障礙的患者嗅束和海馬旁皮質(zhì)下白質(zhì)FA值降低,存在視覺和知覺障礙的患者后部皮質(zhì)下白質(zhì)(如顳葉、枕葉和頂葉)FA值降低[39-40]。視覺信息一般通過兩條并行的路徑處理,即腹側(cè)顳枕葉通路和背側(cè)頂枕葉通路,二者均從初級視覺皮質(zhì)延伸出來,但前者向下至顳葉視覺相關(guān)區(qū)域,后者向上至后頂葉皮質(zhì),發(fā)生帕金森病時兩條通路均出現(xiàn)障礙[28,41]。晚近研究顯示,采用DTI檢測帕金森病患者微弱腦白質(zhì)變化時,MD值較FA值更為敏感[31]。
3.DTI其他參數(shù)與帕金森病認(rèn)知功能障礙的關(guān)系 FA值和MD值是DTI序列最具代表性的參數(shù),其他還包括軸向擴(kuò)散率(AD)和徑向擴(kuò)散率(RD)等。Auning等[28]研究顯示,嗅皮質(zhì)下白質(zhì)RD值和海馬旁皮質(zhì)下白質(zhì)RD值在正常對照者、帕金森病患者和阿爾茨海默病患者中呈線性升高趨勢,頂枕葉RD值在三者中呈線性降低趨勢。此外,帕金森病患者FA值降低主要是由于RD值升高。RD值變化可以歸因于脫髓鞘改變,但并非最重要原因[30]。α-Syn聚集是帕金森病典型病理改變,神經(jīng)膠質(zhì)細(xì)胞的早期變化也為其病理學(xué)特征之一。小膠質(zhì)細(xì)胞的激活伴隨脫髓鞘改變,表明小膠質(zhì)細(xì)胞可能參與引起RD值變化的過程,帕金森病癡呆患者RD值升高代表神經(jīng)變性的早期階段,α-Syn聚集和小膠質(zhì)細(xì)胞活化可能改變軸突纖維的致密性,從而引起RD值升高[42-43]。
4.MRI與DTI在帕金森病認(rèn)知功能障礙診斷中的比較 MRI可以將認(rèn)知功能相關(guān)皮質(zhì)區(qū)域化,并標(biāo)注MRI信號改變,與正常對照者和無癡呆的帕金森病患者相比,帕金森病癡呆患者頭部MRI可見顳頂葉、嗅皮質(zhì)、海馬、前額葉皮質(zhì)和后扣帶回皮質(zhì)萎縮,但白質(zhì)纖維束影像學(xué)信息不豐富;DTI序列可以探測到皮質(zhì)下白質(zhì)改變,從而顯示出微觀結(jié)構(gòu)變化,因此,DTI較MRI更有助于診斷帕金森病認(rèn)知功能障礙[10-11]。
帕金森病患者腦白質(zhì)高信號的發(fā)病機(jī)制與大腦半球白質(zhì)缺血性改變有關(guān),表現(xiàn)為腦室周圍深部白質(zhì)、半卵圓中心、放射冠區(qū)脫髓鞘改變,室管膜層細(xì)胞缺失、神經(jīng)膠質(zhì)細(xì)胞反應(yīng)性增生和軸突減少。有文獻(xiàn)報(bào)道,腦白質(zhì)高信號相關(guān)危險(xiǎn)因素包括高齡、高血壓和糖耐量異常(IGT)等[44],深部白質(zhì)高信號與高齡、高血壓、糖尿病和吸煙相關(guān),腦室周圍白質(zhì)高信號與動脈粥樣硬化相關(guān),而血漿同型半胱氨酸(Hcy)水平與深部白質(zhì)高信號和腦室周圍白質(zhì)高信號均相關(guān)[14]。此外,帕金森病導(dǎo)致的沃勒變性也可能參與腦白質(zhì)高信號的形成[45],是否應(yīng)行抗血小板治療,目前仍無明確結(jié)論,尚待進(jìn)一步深入研究。由于存在腦白質(zhì)高信號的帕金森病患者更易進(jìn)展為輕度認(rèn)知損害和帕金森病癡呆,故對此類患者須定期隨訪。
綜上所述,本文從神經(jīng)元通路、白質(zhì)體積、DTI等方面闡述腦白質(zhì)高信號與帕金森病認(rèn)知功能障礙之間的關(guān)系,白質(zhì)纖維束完整性破壞可能是加速帕金森病認(rèn)知功能障礙的重要原因,DTI作為一種新型影像學(xué)技術(shù),具有無創(chuàng)性且易重復(fù)的優(yōu)點(diǎn),可以作為一種監(jiān)測疾病進(jìn)展的定量評價(jià)方法,全面、準(zhǔn)確地評價(jià)腦白質(zhì)改變,可以作為診斷帕金森病認(rèn)知功能障礙的有效工具,為帕金森病診斷與鑒別診斷提供客觀的影像學(xué)依據(jù),從而有助于明確診斷帕金森病認(rèn)知功能障礙。
[1]Barnum CJ,Tansey MG.Neuroinflammation and non-motor symptoms:the dark passenger of Parkinson's disease?Curr Neurol Neurosci Rep,2012,12:350-358.
[2]Poletti M,Emre M,Bonuccelli U.Mild cognitive impairment and cognitive reserve in Parkinson's disease.Parkinsonism
[3]Relat Disord,2011,17:579-586.Mckinlay A,Grace RC,Dalrymple-Alford JC,Roger D.Cognitive characteristics associated with mild cognitive impairment in Parkinson's disease.Dement Geriatr Cogn
[4]Disord,2009,28:121-129.Zhang JY,Chan P,Xu EH.Attention must be paid to cognitive dysfunction in Parkinson's disease.Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi,2017,17:9-13[.張建蕓,陳彪,許二赫.應(yīng)重視帕金森病認(rèn)知功能障礙.中國現(xiàn)代神經(jīng)疾病雜志,2017,17:9-13.]
[5]Kandiah N,Narasimhalu K,Lau PN,Seah SH,Au WL,Tan LC.Cognitive decline in early Parkinson's disease.Mov Disord,2009,24:605-608.
[6]Kandiah N,Mak E,Ng A,Huang S,Au WL,Sitoh YY,Tan LC.Cerebral white matter hyperintensity in Parkinson's disease:a major risk factor for mild cognitive impairment.Parkinsonism Relat Disord,2013,19:680-683.
[7]Li SH,Chen HB.Mild cognitive impairment in Parkinson's disease.Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi,2016,16:319-323[.李淑華,陳海波.帕金森病輕度認(rèn)知損害.中國現(xiàn)代神經(jīng)疾病雜志,2016,16:319-323.]
[8]Agosta F,Canu E,Stefanova E,Sarro L,Tomic A,?pica V,Comi G,Kostic VS,Filippi M.Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage.Hum Brain Mapp,2014,35:1921-1929.
[9]Lee SH,Kim SS,Tae WS,Lee SY,Lee KU,Jhoo J.Brain volumetry in Parkinson's disease with and without dementia:
[10]where are the differences?Acta Radiol,2013,54:581-586.Hattori T,Orimo S,Aoki S,Ito K,Abe O,Amano A,Sato R,Sakai K,Mizusawa H.Cognitive status correlates with white matter alteration in Parkinson's disease.Hum Brain Mapp,2012,33:727-739.
[11]Deng B,Zhang Y,Wang L,Peng K,Han L,Nie K,Yang H,Zhang L,Wang J.Diffusion tensor imaging reveals white matter changes associated with cognitive status in patients with Parkinson's disease.Am J Alzheimers Dis Other Demen,2013,28:154-164.
[12]Xiong YY,Mok V.Age-related white matter changes.J Aging Res,2011:ID617927.
[13]Mak E,Dwyer MG,Ramasamy DP,Au WL,Tan LC,Zivadinov R,Kandiah N.White matter hyperintensities and mild cognitive impairment in Parkinson's disease.J Neuroimaging,2015,25:
[14]754-760.Ham JH,Yun HJ,Sunwoo MK,Hong JY,Lee JM,Sohn YH,Lee PH.Topography of cortical thinning associated with white matter hyperintensities in Parkinson's disease.Parkinsonism
[15]Relat Disord,2015,21:372-377.Broeders M,De Bie RM,Velseboer DC,Speelman JD,Muslimovic D,Schmand B.Evolution of mild cognitive
[16]impairment in Parkinson disease.Neurology,2013,81:346-352.Hanganu A,Bedetti C,Jubault T,Gagnon JF,Mejia-Constain B,Degroot C,Lafontaine AL,Chouinard S,Monchi O.Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration.Mov Disord,
[17]2013,28:1360-1369.Wen MC,Ng A,Chander RJ,Au WL,Tan LC,Kandiah N.Longitudinal brain volumetric changes and their predictive effects on cognition among cognitively asymptomatic patients with Parkinson's disease.Parkinsonism Relat Disord,2015,21:483-488.
[18]Lee SH,Kim SS,Tae WS,Lee SY,Choi JW,Koh SB,Kwon DY.Regional volume analysis of the Parkinson disease brain in early disease stage:gray matter,white matter,striatum,and thalamus.AJNR Am J Neuroradiol,2011,32:682-687.
[19]Unal-Cevik I,Gursoy-Ozdemir Y,Yemisci M,Lule S,Gurer G,Can A,Müller V,Kahle PJ,Dalkara T.Alpha-synuclein aggregation induced by brief ischemia negatively impacts neuronal survival in vivo:a study in[A30P]alpha-synuclein transgenic mouse.J Cereb Blood Flow Metab,2011,31:913-923.
[20]Sunwoo MK,Jeon S,Ham JH,Hong JY,Lee JE,Lee JM,Sohn YH,Lee PH.The burden of white matter hyperintensities is a predictor of progressive mild cognitive impairment in patients with Parkinson's disease.Eur J Neurol,2014,21:922-928.
[21]Yuan J,Wang H,Wan XH.Cognitive impairment in Parkinson's disease.Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi,2017,17:409-414[.袁晶,王含,萬新華.帕金森病相關(guān)認(rèn)知功能障礙.中國現(xiàn)代神經(jīng)疾病雜志,2017,17:409-414.]
[22]Park HE,Park IS,Oh YS,Yang DW,Lee KS,Choi HS,Ahn KJ,Kim JS.Subcortical whiter matter hyperintensities within the cholinergic pathways of patients with dementia and parkinsonism.J Neurol Sci,2015,353:44-48.
[23]Gomperts SN,Locascio JJ,Marquie M,Santarlasci AL,Rentz DM,Maye J,Johnson KA,Growdon JH.Brain amyloid and cognition in Lewy body diseases.Mov Disord,2012,27:965-973.
[24]Grimmer T,Faust M,Auer F,Alexopoulos P,F?rstl H,Henriksen G,Perneczky R,Sorg C,Yousefi BH,Drzezga A,Kurz A.White matter hyperintensities predict amyloid increase in Alzheimer's disease.Neurobiol Aging,2012,33:2766-2773.
[25]Petrou M,Kotagal V,Bohnen NI.An update on brain imaging in parkinsonian dementia.Imaging Med,2012,4:201-213.
[26]Wang HF,Yu JT,Tang SW,Jiang T,Tan CC,Meng XF,Wang C,Tan MS,Tan L.Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies:systematic review with meta-analysis and trial sequential analysis.J Neurol Neurosurg Psychiatry,2015,86:135-143.
[27]Wen W,Sachdev PS,Chen X,Anstey K.Gray matter reduction is correlated with white matter hyperintensity volume:a voxelbased morphometric study in a large epidemiological sample.Neuroimage,2006,29:1031-1039.
[28]Auning E,Kj?rvik VK,Selnes P,Aarsland D,Haram A,Bj?rnerud A,Hessen E,Esnaashari A,Fladby T.White matter integrity and cognition in Parkinson's disease:a cross-sectional study.BMJ Open,2014,4:E003976.
[29]Kamagata K,Motoi Y,Tomiyama H,Abe O,Ito K,Shimoji K,Suzuki M,Hori M,Nakanishi A,Sano T,Kuwatsuru R,Sasai K,Aoki S,Hattori N.Relationship between cognitive impairment and white-matter alteration in Parkinson's disease with dementia:tract-based spatial statistics and tract-specific analysis.Eur Radiol,2013,23:1946-1955.
[30]Theilmann RJ,Reed JD,Song DD,Huang MX,Lee RR,Litvan I,Harrington DL.White-matter changes correlate with cognitive functioning in Parkinson's disease.Front Neurol,2013,4:37.
[31]Zheng Z,Shemmassian S,Wijekoon C,Kim W,Bookheimer SY, Pouratian N. DTI correlates of distinct cognitive impairments in Parkinson's disease.Hum Brain Mapp,2014,35:
[32]1325-1333.Gallagher C,Bell B,Bendlin B,Palotti M,Okonkwo O,Sodhi A,Wong R,Buyan-Dent L,Johnson S,Willette A,Harding S,Ninman N, Kastman E, Alexander A. White matter microstructural integrity and executive function in Parkinson's
[33]disease.J Int Neuropsychol Soc,2013,19:349-354.Koshimori Y,Segura B,Christopher L,Lobaugh N,Duff-Canning S,Mizrahi R,Hamani C,Lang AE,Aminian K,Houle S,Strafella AP.Imaging changes associated with cognitive abnormalities in Parkinson's disease.Brain Struct Funct,2015,
[34]220:2249-2261.Deng YF,Luo X,Zeng WS,Chen WX,Chen DJ,Wang CL,Huang R.A preliminary study on diffusion tensor imaging of cognitive impairment in Parkinson's disease.Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi,2014,40:489-493[.鄧遠(yuǎn)飛,羅筱,曾文雙,陳文鑫,陳德杰,王成林,黃嶸.帕金森病認(rèn)知障礙彌散張量成像初步研究.中國神經(jīng)精神疾病雜志,2014,40:
[35]489-493.]Chen B,Fan GG,Liu H,Wang S.Changes in anatomical and functional connectivity of Parkinson's disease patients according to cognitive status.Eur J Radiol,2015,84:1318-1324.
[36]Kamagata K,Motoi Y,Abe O,Shimoji K,Hori M,Nakanishi A,Sano T,Kuwatsuru R,Aoki S,Hattori N.White matter alteration of the cingulum in Parkinson disease with and without dementia:evaluation by diffusion tensor tract-specific analysis.AJNR Am J Neuroradiol,2012,33:890-895.
[37]Saito Y,Kawashima A,Ruberu NN,Fujiwara H,Koyama S,Sawabe M,Arai T,Nagura H,Yamanouchi H,Hasegawa M,Iwatsubo T,Murayama S.Accumulation of phosphorylated alphasynuclein in aging human brain.J Neuropathol Exp Neurol,2003,62:644-654.
[38]Braak H,Sandmann-Keil D,Gai W,Braak E.Extensive axonal Lewy neurites in Parkinson's disease:a novel pathological feature revealed by alpha-synuclein immunocytochemistry.Neurosci Lett,1999,265:67-69.
[39]Watson GS,Leverenz JB.Profile of cognitive impairment in
[40]Parkinson's disease.Brain Pathol,2010,20:640-645.Boller F,Passafiume D,Keefe NC,Rogers K,Morrow L,Kim Y.Visuospatial impairment in Parkinson's disease:role of
[41]perceptual and motor factors.Arch Neurol,1984,41:485-490.Diederich NJ,Goetz CG,Stebbins GT.Repeated visual hallucinations in Parkinson's disease as disturbed external/internal perceptions:focused review and a new integrative
[42]model.Mov Disord,2005,20:130-140.Klawiter EC,Schmidt RE,Trinkaus K,Liang HF,Budde MD,Naismith RT,Song SK,Cross AH,Benzinger TL.Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords.Neuroimage,2011,55:1454-1460.
[43]Song SK,Yoshino J,Le TQ,Lin SJ,Sun SW,Cross AH,Armstrong RC.Demyelination increases radial diffusivity in corpus callosum of mouse brain.Neuroimage,2005,26:132-140.
[44]Yamawaki M,Wada-Isoe K,Yamamoto M,Nakashita S,Uemura Y,Takahashi Y,Nakayama T,Nakashima K.Association of cerebral white matter lesions with cognitive function and mood in Japanese elderly people:a populationbased study.Brain Behav,2015,5:E00315.
[45]Shin J,Choi S,Lee JE,Lee HS,Sohn YH,Lee PH.Subcortical white matter hyperintensities within the cholinergic pathways of Parkinson's disease patients according to cognitive status.J Neurol Neurosurg Psychiatry,2012,83:315-321.
Research progress of relationship between white matter hyperintensity and cognitive impairment in Parkinson's disease
HU Fang-fang,ZHANG Zun-sheng,YANG Xin-xin
Department of Neurology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,Jiangsu,China
Corresponding author:ZHANG Zun-sheng(Email:13913473179@163.com)
Parkinson's disease(PD)is a common neurodegenerative disease in the elderly,of which cognitive impairment is the most common non-motor symptom(NMS)affecting the life quality of patients.Cognitive impairment is associated with many factors,and white matter hyperintensity(WMH)is an important pathological change of cognitive impairment in PD.In this paper,we will explain the relationship between WMH and cognitive impairment in PD by the perspective of neuronal pathway,white matter volume change and diffusion tensor imaging(DTI),to provide a new direction for the early diagnosis of PD.
Parkinson disease;Cognition disorders;Magnetic resonance imaging;Review
This study was supported by the National Natural Science Foundation of China(No.81671269)and"Six Peaks of Talents"Support Program of Jiangsu Province,China(No.2015-WSN-064).
10.3969/j.issn.1672-6731.2017.11.012
國家自然科學(xué)基金資助項(xiàng)目(項(xiàng)目編號:81671269);江蘇省“六大人才高峰”資助項(xiàng)目(項(xiàng)目編號:2015-WSN-064)
221002徐州醫(yī)科大學(xué)附屬醫(yī)院神經(jīng)內(nèi)科
張尊勝(Email:13913473179@163.com)
2017-10-25)
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