帕金森病患者伴發(fā)認(rèn)知障礙與非運(yùn)動(dòng)癥狀的相關(guān)性研究

王圣龍,唐金榮

(1. 南京醫(yī)科大學(xué)附屬江蘇盛澤醫(yī)院 神經(jīng)內(nèi)科,江蘇 吳江,215228;2. 南京醫(yī)科大學(xué) 研究生院,江蘇 南京,211166)

?

帕金森病患者伴發(fā)認(rèn)知障礙與非運(yùn)動(dòng)癥狀的相關(guān)性研究

王圣龍1,唐金榮2

(1. 南京醫(yī)科大學(xué)附屬江蘇盛澤醫(yī)院 神經(jīng)內(nèi)科,江蘇 吳江,215228;2. 南京醫(yī)科大學(xué) 研究生院,江蘇 南京,211166)

目的 探討帕金森病(PD)患者伴發(fā)認(rèn)知障礙與非運(yùn)動(dòng)癥狀(NMS)的相關(guān)性。方法 根據(jù)認(rèn)知障礙發(fā)生情況及嚴(yán)重程度，將175例PD患者分為無(wú)認(rèn)知障礙組68例、輕度認(rèn)知障礙(MCI)組92例和癡呆組15例，觀察3組NMS總個(gè)數(shù)以及運(yùn)動(dòng)癥狀前、后期NMS個(gè)數(shù)，比較3組NMS各量表評(píng)分，分析PD伴發(fā)認(rèn)知障礙患者蒙特利爾認(rèn)知評(píng)估量表(MoCA)評(píng)分與NMS發(fā)生的相關(guān)性。結(jié)果 無(wú)認(rèn)知障礙組、MCI組和癡呆組NMS總個(gè)數(shù)依次明顯增多(P<0.01); 3組運(yùn)動(dòng)癥狀前期NMS個(gè)數(shù)比較無(wú)顯著差異(P>0.05),運(yùn)動(dòng)癥狀后期NMS個(gè)數(shù)依次增多(P<0.01)。無(wú)認(rèn)知障礙組、MCI組和癡呆組帕金森氏病綜合評(píng)分量表(UPDRS)、匹茨堡睡眠質(zhì)量指數(shù)量表(PSQI)、自主神經(jīng)癥狀量表(SCOPA-AUT)評(píng)分依次顯著升高(P<0.05或P<0.01); MCI組和癡呆組愛(ài)潑沃斯思睡量表(ESS)評(píng)分顯著高于無(wú)認(rèn)知障礙組(P<0.01),但2組間比較無(wú)顯著差異(P>0.05); 癡呆組漢密爾頓焦慮量表(HAMA)、漢密爾頓抑郁量表(HAMD)及不寧腿綜合征嚴(yán)重程度評(píng)定量表(RLSRS)評(píng)分均顯著高于MCI組和無(wú)認(rèn)知障礙組(P<0.05或P<0.01),但MCI組和無(wú)認(rèn)知障礙組比較無(wú)顯著差異(P>0.05)。相關(guān)性分析表明,PD伴發(fā)認(rèn)知障礙患者的蒙特利爾認(rèn)知評(píng)估量表(MoCA)評(píng)分與UPDRS、ESS、PSQI、SCOPA-AUT評(píng)分呈明顯負(fù)相關(guān)(P<0.05)。結(jié)論 PD患者的NMS在運(yùn)動(dòng)障礙出現(xiàn)后隨認(rèn)知障礙的加重而加重；隨著認(rèn)知障礙的加重，PD伴發(fā)認(rèn)知障礙患者整體精神和情緒狀況、睡眠障礙及自主神經(jīng)功能障礙越嚴(yán)重。

帕金森病; 認(rèn)知障礙; 非運(yùn)動(dòng)癥狀; 生活質(zhì)量

帕金森病(PD)是中老年人常見(jiàn)的神經(jīng)系統(tǒng)變性疾病，臨床主要表現(xiàn)為靜止性震顫、運(yùn)動(dòng)遲緩、肌強(qiáng)直及姿勢(shì)不穩(wěn)等癥狀[1]。近年來(lái)，越來(lái)越多研究[2-3]證實(shí)，除典型運(yùn)動(dòng)癥狀外,PD還伴有一些非運(yùn)動(dòng)癥狀(NMS),且已成為影響患者生活質(zhì)量的重要原因。認(rèn)知障礙是NMS的重要表現(xiàn)。Aarsland等[4-5]研究發(fā)現(xiàn)，在新近診斷為PD的患者中有19%～36%存在認(rèn)知障礙,20%～57%于確診后3～5年出現(xiàn)輕度認(rèn)知障礙(MCI),且隨著病情加重，部分患者會(huì)進(jìn)一步發(fā)展為癡呆。截至目前為止，國(guó)內(nèi)關(guān)于PD伴發(fā)認(rèn)知障礙與NMS關(guān)系的研究較為少見(jiàn)。本研究采用NMS相關(guān)量表對(duì)PD伴發(fā)認(rèn)知障礙患者的NMS臨床特征進(jìn)行分析，旨在為此類(lèi)患者預(yù)后評(píng)估與治療提供理論依據(jù)。

1 資料與方法

1.1 一般資料

選取2013年3月—2016年3月收治的PD患者175例，均符合《中國(guó)帕金森病的診斷標(biāo)準(zhǔn)》[6],排除繼發(fā)性帕金森綜合征、帕金森疊加綜合征及特發(fā)性震顫。其中男89例，女86例；年齡36～84歲，平均(60.5±9.4)歲；病程9個(gè)月～25年，中位病程3.6年。根據(jù)是否伴發(fā)認(rèn)知障礙，將患者分為無(wú)認(rèn)知障礙組68例和認(rèn)知障礙組107例，再根據(jù)認(rèn)知障礙的嚴(yán)重程度將患者分為MCI組92例和癡呆組15例。MCI組男46例，女46例；年齡36～81歲，平均(60.20±9.61)歲；病程11個(gè)月～22年，中位病程3.41年。癡呆組男7例，女8例；年齡53～84歲，平均(61.21±10.42)歲；病程14個(gè)月～25年，中位病程3.80年。無(wú)認(rèn)知障礙組男36例，女32例；年齡36～79歲，平均(58.9±10.1)歲；病程9個(gè)月～14年，中位病程3.13年。3組一般資料比較無(wú)顯著差異(P>0.05)，具有可比性。

1.2 方法

① 采用PD非運(yùn)動(dòng)癥狀問(wèn)卷(NMSQ)篩查所有患者的NMS,對(duì)NMS總個(gè)數(shù)及運(yùn)動(dòng)癥狀前、后期NMS個(gè)數(shù)進(jìn)行統(tǒng)計(jì); ② 采用蒙特利爾認(rèn)知評(píng)估量表(MoCA)對(duì)認(rèn)知功能進(jìn)行評(píng)估; ③ 采用帕金森氏病綜合評(píng)分量表(UPDRS)對(duì)整體精神和情緒狀況進(jìn)行評(píng)估，漢密爾頓焦慮量表(HAMA)和漢密爾頓抑郁量表(HAMD)分別對(duì)焦慮和抑郁狀況進(jìn)行評(píng)估; ④ 采用愛(ài)潑沃斯思睡量表(ESS)和匹茨堡睡眠質(zhì)量指數(shù)量表(PSQI)分別對(duì)日間思睡程度和整體睡眠質(zhì)量進(jìn)行評(píng)估; ⑤ 采用PD自主神經(jīng)癥狀量表(SCOPA-AUT)對(duì)自主神經(jīng)癥狀進(jìn)行評(píng)估; ⑥ 采用疲勞量表(FS-14)對(duì)疲勞及其嚴(yán)重程度進(jìn)行評(píng)估; ⑦ 采用不寧腿綜合征嚴(yán)重程度評(píng)定量表(RLSRS)對(duì)不寧腿綜合征的發(fā)生情況及嚴(yán)重程度進(jìn)行評(píng)估。

1.3 觀察指標(biāo)

觀察無(wú)認(rèn)知障礙組、MCI組和癡呆組NMS總個(gè)數(shù)以及運(yùn)動(dòng)癥狀前、后期NMS個(gè)數(shù)，比較3組NMS各量表評(píng)分，分析PD伴發(fā)認(rèn)知障礙患者M(jìn)oCA評(píng)分與NMS發(fā)生的相關(guān)性。

1.4 統(tǒng)計(jì)學(xué)方法

2 結(jié) 果

2.1 3組NMS發(fā)生情況比較

無(wú)認(rèn)知障礙組、MCI組和癡呆組NMS總個(gè)數(shù)依次明顯增多，差異有統(tǒng)計(jì)學(xué)意義(P<0.01); 3組運(yùn)動(dòng)癥狀前期NMS個(gè)數(shù)比較無(wú)顯著差異(P>0.05),運(yùn)動(dòng)癥狀后期NMS個(gè)數(shù)依次增多，其中癡呆組NMS個(gè)數(shù)較無(wú)認(rèn)知障礙組、MCI組顯著增多(P<0.01)。見(jiàn)表1。

2.2 3組NMS各量表評(píng)分比較

無(wú)認(rèn)知障礙組、MCI組和癡呆組UPDRS、PSQI、SCOPA-AUT評(píng)分依次顯著升高，組間比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05或P<0.01); MCI組和癡呆組ESS評(píng)分顯著高于無(wú)認(rèn)知障礙組(P<0.01),但MCI組和癡呆組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05); 癡呆組HAMA、HAMD及RLSRS評(píng)分均顯著高于MCI組和無(wú)認(rèn)知障礙組(P<0.05或P<0.01),但MCI組和無(wú)認(rèn)知障礙組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表2。

表1 3組NMS發(fā)生情況比較

表2 3組NMS各量表評(píng)分比較 分

2.3 PD伴發(fā)認(rèn)知障礙患者M(jìn)oCA評(píng)分與NMS發(fā)生的相關(guān)性

Spearman相關(guān)性分析表明,PD伴發(fā)認(rèn)知障礙患者的MoCA評(píng)分與UPDRS、ESS、PSQI、SCOPA-AUT評(píng)分呈明顯負(fù)相關(guān)(r=-0.246,P=0.034;r=-0.192,P=0.025;r=-0.219,P=0.032;r=-0.284,P=0.039),而與HAMA、HAMD、FS-14、RLSRS評(píng)分無(wú)明顯相關(guān)性(P>0.05)。

3 討 論

作為老年人常見(jiàn)致殘?jiān)蛑?PD不僅嚴(yán)重影響患者運(yùn)動(dòng)功能，還對(duì)其認(rèn)知功能造成一定損傷，嚴(yán)重者會(huì)引發(fā)癡呆[7]。PD患者往往在癡呆發(fā)生前存在不同程度的認(rèn)知障礙，且以MCI為主[8]。研究[9]發(fā)現(xiàn)，認(rèn)知障礙的嚴(yán)重程度與大腦皮層，尤其是顳葉新皮層路易小體的負(fù)荷密切相關(guān)。根據(jù)路易小體在腦部沉積的部位不同,Jellinger PD病理可分為6期[10]: Ⅰ期表現(xiàn)為便秘、嗅覺(jué)障礙，嗅球、嗅束、迷走神經(jīng)背核為受累部位；Ⅱ期表現(xiàn)為自主神經(jīng)功能障礙、睡眠障礙、抑郁、疲勞等，下位腦干脊核、藍(lán)斑等核團(tuán)為受累部位；Ⅲ、Ⅳ期表現(xiàn)為各種運(yùn)動(dòng)癥狀，中腦黑質(zhì)及其他深部核團(tuán)為受累部位; Ⅴ、Ⅵ期表現(xiàn)為各種精神癥狀及認(rèn)知障礙，新皮質(zhì)、邊緣系統(tǒng)為受累部位。NMS通常發(fā)生于Ⅲ、Ⅳ期的運(yùn)動(dòng)癥狀前后，而認(rèn)知障礙發(fā)生于Ⅴ、Ⅵ期，通常在運(yùn)動(dòng)癥狀后出現(xiàn)?？梢?jiàn),PD伴發(fā)認(rèn)知障礙患者存在較多的NMS[11]。本研究結(jié)果顯示，無(wú)認(rèn)知障礙組、MCI組和癡呆組NMS總個(gè)數(shù)依次明顯增多，組間比較差異有統(tǒng)計(jì)學(xué)意義；3組運(yùn)動(dòng)癥狀前期NMS個(gè)數(shù)比較無(wú)顯著差異，運(yùn)動(dòng)癥狀后期NMS個(gè)數(shù)依次增多，說(shuō)明NMS廣泛存在于PD患者中，且運(yùn)動(dòng)障礙出現(xiàn)后隨認(rèn)知障礙的加重而呈明顯增加趨勢(shì)，與Rana等[12-13]報(bào)道一致。

本研究采用NMS相關(guān)量表對(duì)PD伴發(fā)認(rèn)知障礙患者的NMS進(jìn)行分析，發(fā)現(xiàn)無(wú)認(rèn)知障礙組、MCI組和癡呆組UPDRS、PSQI、SCOPA-AUT評(píng)分依次顯著升高(P<0.05或P<0.01),說(shuō)明PD伴發(fā)認(rèn)知障礙患者的整體精神、情緒狀況、睡眠質(zhì)量及自主神經(jīng)功能障礙較未發(fā)生認(rèn)知障礙者更為嚴(yán)重，且上述NMS隨認(rèn)知障礙的加重而明顯加重，可能與路易小體在迷走神經(jīng)背核、下位腦干脊核等部位沉積數(shù)量有關(guān)，沉積數(shù)量越多,NMS越嚴(yán)重[14-16]; MCI組和癡呆組ESS評(píng)分顯著高于無(wú)認(rèn)知障礙組，但MCI組和癡呆組比較無(wú)顯著差異，說(shuō)明認(rèn)知障礙患者日間思睡程度較未發(fā)生者更為嚴(yán)重，但日間思睡與認(rèn)知障礙的嚴(yán)重程度無(wú)關(guān)，考慮可能與睡眠結(jié)構(gòu)的變化、路易小體在相關(guān)睡眠結(jié)構(gòu)的沉積、夜間睡眠障礙、出現(xiàn)的抑郁及相關(guān)藥物治療有關(guān)[17-19]; 癡呆組HAMA、HAMD及RLSRS評(píng)分均顯著高于MCI組和無(wú)認(rèn)知障礙組，但MCI組和無(wú)認(rèn)知障礙組比較差異無(wú)統(tǒng)計(jì)學(xué)意義，說(shuō)明伴發(fā)嚴(yán)重認(rèn)知障礙的患者具有明顯的焦慮、抑郁、不寧腿綜合征等癥狀。進(jìn)一步分析PD伴發(fā)認(rèn)知障礙患者的認(rèn)知功能與NMS的相關(guān)性，結(jié)果發(fā)現(xiàn)PD伴發(fā)認(rèn)知障礙患者的MoCA評(píng)分與UPDRS、ESS、PSQI、SCOPA-AUT評(píng)分呈明顯負(fù)相關(guān)，提示PD伴發(fā)認(rèn)知障礙患者隨著認(rèn)知障礙的加重，其整體精神和情緒狀況、睡眠障礙及自主神經(jīng)功能障礙呈明顯加重趨勢(shì)。

綜上所述,NMS廣泛存在于PD患者中，且運(yùn)動(dòng)障礙出現(xiàn)后隨認(rèn)知障礙的加重而呈明顯增加趨勢(shì)，嚴(yán)重影響患者的生活質(zhì)量和日常生活能力；隨著認(rèn)知障礙的加重，PD伴發(fā)認(rèn)知障礙患者整體精神和情緒狀況、睡眠障礙及自主神經(jīng)功能障礙越嚴(yán)重。

[1] 楊雪霞,李鵬. 帕金森病非運(yùn)動(dòng)癥狀患者的臨床特征及影響因素[J]. 中國(guó)老年學(xué)雜志,2013,33(6)：1260-1262.

[2] Ou R,Yang J,Cao B,et al. Progression of non-motor symptoms in Parkinson′s disease among different age populations: A two-year follow-up study[J]. J Neurol Sci,2016,360: 72-77.

[3] Cugusi L,Solla P,Serpe R,et al. Effects of a Nordic Walking program on motor and non-motor symptoms,functional performance and body composition in patients with Parkinson′s disease[J]. NeuroRehabilitation,2015,37(2): 245-254.

[4] Aarsland D,Bronnick K,Larsen J P,et al. Cognitive impairment in incident,untreated Parkinson disease: the Norwegian ParkWest study[J]. Neurology,2009,72(13): 1121-1126.

[5] Leroi I,Pantula H,McDonald K,et al. Neuropsychiatric symptoms in Parkinson′s disease with mild cognitive impairment and dementia[J]. Parkinsons Dis,2012,2012: 308097.

[6] 中華醫(yī)學(xué)會(huì)神經(jīng)病學(xué)分會(huì)帕金森病及運(yùn)動(dòng)障礙學(xué)組,中國(guó)醫(yī)師協(xié)會(huì)神經(jīng)內(nèi)科醫(yī)師分會(huì)帕金森病及運(yùn)動(dòng)障礙專(zhuān)業(yè). 中國(guó)帕金森病的診斷標(biāo)準(zhǔn)(2016版)[J]. 中華神經(jīng)科雜志,2016,49(4): 268-271.

[7] Espay A J,LeWitt P A,Hauser R A,et al. Neurogenic orthostatic hypotension and supine hypertension in Parkinson′s disease and related synucleinopathies: prioritisation of treatment targets[J]. Lancet Neurol,2016,15(9): 954-966.

[8] Seubert-Ravelo A N,Yáu ez-Téllez M G,Salgado-Ceballos H,et al. Mild cognitive impairment in patients with early-onset Parkinson′s disease[J]. Dement Geriatr Cogn Disord,2016,42(1/2): 17-30.

[9] Garcia-Ptacek S,Kramberger M G. Parkinson disease and dementia[J]. J Geriatr Psychiatry Neurol,2016,29(5): 261-270.

[10] Jellinger K A. Critical evaluation of the Braak staging scheme for Parkinson′s disease[J]. Ann Neurol,2010,67(4): 550.

[11] Pont-Sunyer C,Hotter A,Gaig C,et al. The onset of nonmotor symptoms in Parkinson′s disease (the ONSET PD study)[J]. Mov Disord,2015,30(2): 229-237.

[12] Rana A Q,Ahmed U S,Chaudry Z M,et al. Parkinson′s disease: a review of non-motor symptoms[J]. Expert Rev Neurother,2015,15(5): 549-562.

[13] Khoo T K,Yarnall A J,Duncan G W,et al. The spectrum of nonmotor symptoms in early Parkinson disease[J]. Neurology,2013,80(3): 276-281.

[14] Garcia-Ruiz P J,Chaudhuri K R,Martinez-Martin P. Non-motor symptoms of Parkinson's disease A review…from the past[J]. J Neurol Sci,2014,338(1/2): 30-33.

[15] 黃靜,張玉虎,王麗娟. 帕金森病睡眠障礙與認(rèn)知功能損害關(guān)系的研究進(jìn)展[J]. 中華老年心腦血管病雜志,2013,5(5): 554-556.

[16] 李靜,張艷玲,胡曉飛,等. 帕金森病運(yùn)動(dòng)亞型的認(rèn)知功能障礙特征研究[J]. 第三軍醫(yī)大學(xué)學(xué)報(bào),2015,37(22): 2285-2288.

[17] 李芳菲,馮濤. 2013年歐洲神經(jīng)病學(xué)聯(lián)盟帕金森病診斷指南解讀[J]. 中國(guó)實(shí)用內(nèi)科雜志,2013,33(11): 862-865.

[18] 范玲玲,鄧博,閆君寶,等. 5-羥色胺-7受體激動(dòng)劑對(duì)帕金森病模型大鼠內(nèi)側(cè)前額葉皮層錐體神經(jīng)元興奮性的影響[J]. 南方醫(yī)科大學(xué)學(xué)報(bào),2016,36(6): 756-762.

[19] 黎羅明,陳志斌. 帕金森病遺傳基因的研究進(jìn)展[J]. 海南醫(yī)學(xué)院學(xué)報(bào),2012,18(9): 1339-1342.

Study on correlation between cognitive impairment and non-motor symptoms in patients with Parkinson′s disease

WANG Shenglong1,TANG Jinrong2

(1.DepartmentofNeurology,JiangsuShengzeHospitalAffiliatedtoNanjingMedicalUniversity,Wujiang,Jiangsu,215228; 2.PostgraduateSchoolofNanjingMedicalUniversity,Nanjing,Jiangsu,211166)

Objective To explore the correlation between cognitive impairment and non-motor symptoms (NMS) in patients with Parkinson′s disease (PD). Methods A total of 175 patients with PD were divided into non-cognitive impairment group (n=68),mild cognitive impairment (MCI) group (n=92) and dementia group (n=15) according to the developmental conditions and severity of cognitive impairment. Total NMS numbers as well as NMS numbers in prophase and postphase motor symptoms were observed in all groups. NMS scale score was compared among three groups and correlation between Montreal cognitive assessment (MoCA) score and NMS in patients with PD complicated with cognitive impairment was analyzed. Results Total NMS number increased in sequence in non-cognitive impairment group,MCI group and dementia group (P<0.01). There was no significant difference among 3 groups in NMS number in prophase motor symptoms (P>0.05),but the number increased in sequence in postphase motor symptoms (P<0.01). Unified Parkinson′s disease rating scale (UPDRS),Pittsburgh sleep quality index (PSQI) and the scale for outcomes in PD for autonomic symptoms (SCOPA-AUT) scores increased in sequence in non-cogni-tive impairment group,MCI group and dementia group (P<0.05 orP<0.01). MCI group and dementia group were significantly higher in Epworth sleepiness scale (ESS) score than non-cognitive impairment group (P<0.01),but there was no significant difference between them (P>0.05). Dementia group was notably higher in Hamilton anxiety scale (HAMA),Hamilton depression scale (HAMD) and restless legs syndrome rating scale (RLSRS) score than other two groups (P<0.05 orP<0.01),but there were no significant differences between MCI group and non-cognitive impairment group (P>0.05). Correlation analysis showed that MoCA score in patients with PD complicated with cognitive impairment was closely associated with PDRS,ESS,PSQI and SCOPA-AUT scores (P<0.05). Conclusion NMS aggravates along with the severity of cognitive impairment in patients with PD after the appearance of dyskinesia. With the aggravation of cognitive impairment,the whole spirit,emotional status,somnipathy and autonomic nervous dysfunction are increasingly severer in patients with PD complicated with cognitive impairment.

Parkinson′s disease; cognitive impairment; non-motor symptom; quality of life

2016-04-20

中國(guó)高校醫(yī)學(xué)期刊臨床專(zhuān)項(xiàng)資金(11526810)

R 742.5

A

1672-2353(2016)21-017-04

10.7619/jcmp.201621006