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Chinese Journal of Alzheimer's Disease and Related Disorders

Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders      Editor in chief: Jun WANG

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Original article

The clinical features and correlative factors of apathy in patients with Parkinson's disese

  • HE Shijia , 1 ,
  • WANG Yirong 2 ,
  • SUN Ling 1 ,
  • CHENG Bo 1 ,
  • YU Juming 1 ,
  • ZHANG Shushan , 1
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  • 1 Department of Neurology of Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China
  • 2 Department of Neurology of Chengdu Second People's Hospital, Chengdu, Sichuan 610000, China

Received date: 2020-08-01

  Revised date: 2021-01-05

  Online published: 2021-03-25

Abstract

Objectives: To survey correlative factors of apathy through investigating clinical features of motor symptoms and non-motor symptoms (NMS) in Parkinson's disease (PD) patients.

Methods:

Our cross-sectional study included 120 clinical diagnosed PD patients from neurology department, Affiliated Hospital of North Sichuan Medical College. Apathy was evaluated using the Lille Apathy Rating Scale (LARS) and Non-Motor Symptom Scale (NMSS) were used to access NMS.

Results:

Apathy was observed in 37.5% of PD patients in our study. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were significantly lower in PD patients with apathy. The levodopa equivalent daily dose (LEDD), proportion of treatment with levodopa, scores of the H-Y stage, the Unified Parkinson’s Disease Rating Scale part III (UPDRS III), the 39-item PD Questionnaire (PDQ-39) and the Beck Depression Inventory (BDI) were significantly higher in PD patients with apathy. The prevalence of attention/memory domain with items “concentration” and “recent memory loss”, gastrointestinal domain with item “constipation”, urinary domain with items “nocturia” and “frequency micturition”, and items “difficulty falling asleep”, “lost of interest”, “apathy” and “feeling sad” were significantly higher in PD patients with apathy. The logistic regression indicated that lower MoCA scores, higher BDI scores and presence of urinary domain symptoms in NMSS were associated with apathy in PD.

Conclusions:

Apathy was common in PD patients. PD patients with cognitive dysfunction, depression and urinary symptoms were prone to present with apathy.

Cite this article

HE Shijia , WANG Yirong , SUN Ling , CHENG Bo , YU Juming , ZHANG Shushan . The clinical features and correlative factors of apathy in patients with Parkinson's disese[J]. Chinese Journal of Alzheimer's Disease and Related Disorders, 2021 , 4(1) : 37 -41 . DOI: 10.3969/j.issn.2096-5516.2021.01.006

帕金森病(Parkinson's disease,PD)是中老年人第二常见的神经变性疾病,常合并嗅觉障碍、睡眠障碍、自主神经功能障碍和精神障碍等非运动症状(the Non-Motor Symptoms, NMS)。淡漠是PD常见的NMS,文献报道的发生率约13.9%~70%[1]。淡漠会导致PD患者日常生活能力下降,严重影响生活质量,给照料者也带来沉重负担[2]。目前国内对PD淡漠的研究相对较少,且与国外报道存在一定差异,故研究PD淡漠的发生率及其相关因素,以期早发现早治疗,能更好地改善PD患者预后。

1 研究对象和研究方法

1.1 研究对象

本横断面研究纳入2018年1月到2019年12月就诊于川北医学院附属医院神经内科临床确诊的PD患者120例。纳入标准:符合2016年中华医学会神经病学分会帕金森病及运动障碍学组的诊断标准[3]。排除标准:非典型及继发性帕金森综合征的患者;不能配合进行运动症状及NMS评定的患者;诊断为重度抑郁及帕金森病痴呆的患者。采集临床数据及评估量表时患者均处于开期并处于安静环境。量表评估均由两名神经内科医师在经过严格的量表评估一致性检验后进行评定。

1.2 临床数据的采集

应用自制的量表采集PD患者的人口学信息,包括:性别、年龄、教育年限、发病年龄、病程、合并内科疾病、家族史等。左旋多巴等效剂量(levodopa equivalent daily dose,LEDD)采用通用的计算公式计算[4]

1.3 淡漠的评估

使用Lille淡漠量表(the Lille Apathy Rating Scale,LARS)评估淡漠,LARS评分≥-21认为有淡漠,LARS评分<-21认为无淡漠[5]

1.4 运动症状的评估

使用统一PD评定量表第三部分(the Unified Parkinson's Disease Rating Scale partIII,UPDRS III)及H-Y分级评估PD患者的运动功能和残疾程度。

1.5 非运动症状的评估

分别使用非运动症状量表(the Non-Motor Symptoms Scale,NMSS)[6]、蒙特利尔认知评估量表(the Montreal Cognitive Assessment, MoCA)[7]、Beck抑郁问卷(the Beck Depression Inventory,BDI)、额叶功能评定量表(the Frontal Assessment Battery,FAB)[8]全面评估PD患者NMS、认知功能、抑郁状况及额叶功能。

1.6 生活质量的评估

使用PD生活质量问卷39(the 39-item Parkinson's Disease Questionnaire,PDQ-39)评估PD患者的生活质量[9]

1.7 统计学分析

所有统计学分析均应用SPSS 24.0软件包完成。连续性变量用均值±标准差(x±s)表示,两组间连续性变量比较用t检验;分类变量用百分数表示,两组间分类变量比较用χ2检验。淡漠相关因素分析采用Logistic回归分析。P<0.05时有显著统计学差异。

2 结果

2.1 PD患者人口学及临床特征和情感淡漠的发生情况

120例PD患者中有75(62.5%)例为男性,45(37.5%)例为女性,平均年龄58.83 ± 11.91岁,平均病程58±1.48年,平均H-Y分级2.07±0.65。PD伴淡漠患者LEDD和使用左旋多巴比例明显高于PD不伴淡漠患者;人口学特征、临床特征及剩下的药物使用比例在两组间无明显差异,见表1。45例(37.5%)PD患者合并淡漠,其中单纯淡漠15例(12.5%),同时合并抑郁29例(24.17%)。
表1 PD人口学特征及临床特征

Tab. 1 Demographic and clinical features of PD patients

项目 PD总体 PD伴淡漠 PD不伴淡漠 P
患者人数 120(100%) 45(37.5%) 75(62.5%) -
人口学特征
男性 75(62.5%) 25(55.6%) 50(66.7%) 0.224
平均年龄(年) 58.83 ± 11.91 59.98 ± 10.30 56.64 ± 13.29 0.417
起病年龄(年) 57.12 ± 12.16 57.94 ± 10.05 56.46 ± 12.91 0.581
病程(年) 1.58 ± 1.48 1.71 ± 1.66 1.51 ± 1.37 0.478
教育年限(年) 11.11 ± 3.65 10.25 ± 3.96 11.49 ± 3.47 0.110
LARS -23.70 ± 10.86 -12.02 ± 8.13 -30.71 ± 4.22 <0.001
临床特征
PD家族史 21(17.8%) 7(16.3%) 14(18.7%) 0.744
高血压 17(14.3%) 6(13.3%) 11(14.9%) 0.817
糖尿病 9(7.6%) 4(8.9%) 5(6.8%) 0.945
吸烟 33(27.5%) 11(24.4%) 22(29.3%) 0.561
饮酒 28(23.3%) 13(28.9%) 15(20.0%) 0.265
药物使用
LEDD 180.92 ± 195.69 233.33 ± 177.27 148.06 ± 200.74 0.026
左旋多巴 66(55.5%) 34(75.6%) 32(43.2%) 0.010
多巴胺受体激动剂 49(41.2%) 21(46.7%) 28(37.8%) 0.343
金刚烷胺 25(21.0%) 13(28.9%) 12(16.2%) 0.100
苯海索 10(8.4%) 4(8.9%) 6(8.1%) 1.000
COMT 3(2.5%) 0(0.0%) 3(4.1%) 0.289
MAO-B抑制剂 2(1.7%) 1(2.2%) 1(1.4%) 1.000

Note: Abbreviations: PD: Parkinson's disease, LEDD: levodopa equivalent daily dose, LARS: the Lille Apathy Rating Scale, COMT: Catechol-O-methyltransferase, MAO-B: Monoamine Oxidase B

2.2 PD伴淡漠和不伴淡漠患者运动症状、部分NMS和PDQ-39得分比较

PD伴淡漠患者H-Y分级、UPDRS III总分、PDQ-39得分及BDI得分明显高于PD不伴淡漠患者。PD伴淡漠患者MoCA得分、FAB 得分明显低于PD不伴淡漠患者,见表2。
表2 PD伴淡漠与不伴淡漠患者运动症状和部分NMS比较

Tab. 2 Motor symptom and partial NMS between PD patients with and without apathy

项目 PD总体 PD伴淡漠 PD不伴淡漠 P
严重程度
H-Y分级 2.07 ± 0.65 2.34 ± 0.65 1.91 ± 0.59 <0.001
UPDRS III得分 25.54 ± 12.47 30.38 ± 12.98 22.63 ± 11.27 0.001
MoCA得分 27.91 ± 21.00 24.66 ± 2.57 26.35 ± 2.60 <0.001
FAB得分 16.17 ± 1.74 15.53 ± 2.00 16.51 ± 1.50 0.004
BDI得分 5.10 ± 4.40 6.70 ± 4.95 4.13 ± 3.75 0.004
PDQ-39得分 25.86 ± 2.69 38.28 ± 22.62 22.15 ± 17.73 <0.001

Note: Abbreviations: PD: Parkinson's disease, UPDRS III: the Unified Parkinson's Disease Rating Scale part III, MoCA: the Montreal Cognitive Assessment, FAB: the Frontal Assessment Battery, BDI: the Beck Depression Inventory, PDQ-39: the 39-item Parkinson's disease Questionnaire

2.3 PD伴淡漠和PD不伴淡漠患者NMS比较

PD伴淡漠患者NMSS总分明显高于PD不伴淡漠患者;PD伴淡漠患者注意/记忆亚项及条目注意力缺乏和近记忆下降、胃肠道症状亚项及条目便秘、泌尿系统症状亚项及条目尿频和夜尿增多和入睡困难、丧失兴趣、淡漠、高兴不起来等条目的发生率明显高于PD不伴淡漠患者,剩下的亚项和条目发生率在两组间无明显差异,见表3。
表3 PD伴淡漠与不伴淡漠患者NMS比较

Tab. 3 Prevalence of NMS between PD patients with and without apathy

项目 PD总体 PD伴淡漠 PD不伴淡漠 P
1.心血管症状 26(21.7%) 6(13.3%) 20(26.7%) 0.086
头晕 24(20.0%) 6(13.3%) 18(24.0%) 0.157
跌倒 5(4.2%) 1(2.2%) 4(5.3%) 0.723
2.睡眠/疲乏 88(73.9%) 37(82.2%) 51(68.9%) 0.109
日间嗜睡 53(44.2%) 21(46.7%) 32(42.7%) 0.669
疲乏 61(50.8%) 24(53.3%) 37(49.3%) 0.671
入睡困难 59(49.2%) 28(62.2%) 31(41.3%) 0.027
不宁腿 25(21.0%) 11(24.4%) 14(18.9%) 0.473
3.情绪认知 79(66.4%) 33(75.5%) 46(61.3%) 0.128
丧失兴趣 48(40.3%) 23(52.3%) 25(33.3%) 0.042
缺乏动力 49(41.2%) 23(52.3%) 26(34.7%) 0.060
紧张 36(30.3%) 17(38.6%) 19(25.3%) 0.127
悲伤 60(50.4%) 27(61.4%) 33(44.0%) 0.067
淡漠 30(25.2%) 20(45.5%) 10(13.3%) <0.001
高兴不起来 38(31.9%) 23(52.3%) 15(20.0%) <0.001
4.知觉/幻觉 11(9.2%) 5(11.1%) 6(8.0%) 0.567
视幻觉 3(2.5%) 2(4.4%) 1(1.3%) 0.651
妄想 1(0.8%) 1(2.2%) 0(0.0%) 0.375
复视 8(6.7%) 3(6.7%) 5(6.7%) 1.000
5.注意/记忆 90(75.6%) 41(91.1%) 49(66.2%) 0.004
注意力缺乏 34(28.3%) 18(40.0%) 16(21.3%) 0.028
近记忆下降 77(64.2%) 37(82.2%) 40(53.3%) 0.001
忘记做事情 48(40.3%) 22(48.9%) 26(35.1%) 0.138
6.胃肠道症状 67(56.3%) 31(70.5%) 36(48.0%) 0.017
流涎 20(16.7%) 8(17.8%) 12(16.0%) 0.800
吞咽困难 26(21.8%) 13(29.5%) 13(17.3%) 0.120
便秘 54(45.0%) 27(60.0%) 27(36.0%) 0.011
7.泌尿系统症状 75(62.5%) 36(80.0%) 39(52.0%) 0.002
尿急 40(33.3%) 19(42.2%) 21(28.0%) 0.110
尿频 37(30.8%) 21(46.7%) 16(21.3%) 0.004
夜尿增多 64(53.3%) 31(68.9%) 33(44.0%) 0.008
8.性功能症状 69(59.5%) 26(60.5%) 43(58.9%) 0.869
性欲改变 66(56.9%) 25(58.1%) 41(56.2%) 0.836
性生活障碍 62(53.4%) 24(55.8%) 38(52.1%) 0.695
9.其他 86(71.7%) 33(73.3%) 53(70.7%) 0.754
疼痛 50(41.7%) 19(42.2%) 31(41.3%) 0.924
味觉减退 45(37.5%) 17(37.8%) 28(37.3%) 0.961
体重改变 17(14.2%) 8(17.8%) 9(12.0%) 0.380
多汗 34(28.3%) 15(33.3%) 19(25.3%) 0.346
NMSS总分 39.47 ± 27.81 51.07 ± 29.97 32.774 ± 24.27 0.001

Note: Abbreviations: PD: Parkinson's disease, NMS: Non-Motor Symptom, NMSS: the Non-Motor Symptoms Scale

2.4 PD患者情感淡漠相关因素的Logistic回归分析

单因素分析中有明显差异的变量纳入进一步Logistic回归分析,发现MoCA得分低、BDI得分高、泌尿系统症状与PD淡漠有关,见表4。
表4 PD淡漠相关因素的logistic回归分析

Tab. 4 Correlative factors of apathy in PD patients based on logistic regression analysis

项目 OR 95%可信区间 P
MoCA得分 -0.241 0.625-0.988 0.039
BDI得分 0.218 1.047-1.478 0.013
泌尿系统症状 2.322 2.114-49.208 0.004

Note: Abbreviations: PD: Parkinson's disease, MoCA: the Montreal Cognitive Assessment, BDI: the Beck Depression Inventory

3 讨论

淡漠是一种行为综合征,以动机缺失或减弱为特征,表现为情感、目标导向行为和认知活动的减少[10]。本研究发现PD患者淡漠达37.5%,与国内外报道基本一致[1,11];其次,与既往研究一致,我们发现认知障碍及抑郁与PD淡漠有关;最后,本研究还发现泌尿系统症状与PD淡漠有关,尚未发现文献报道。
认知障碍是PD常见的NMS,淡漠与认知障碍关系密切,本研究也证实认知功能障碍是PD淡漠的相关因素,与国内外研究基本一致[10,12,13]。近期刘辉等发现初诊未治的PD淡漠与特定认知域如执行功能有关[14],Gabriella等也证实PD单纯性淡漠与执行功能障碍相关[15],进一步的研究发现PD伴淡 漠患者决策能力受损明显[16],后续的研究我们将进一步详细评估认知域以明确不同认知域与PD淡漠的 关系。此外,淡漠还是帕金森痴呆的强预测因素,Santangelo等发现强化认知刺激及训练可以减缓认知功能下降,同时也可以减轻淡漠,提示认知干预治疗淡漠可能有效[15]
抑郁是PD另一常见的NMS,可出现在运动症状之前[17]。既往研究认为淡漠与抑郁属同一症候群,与多巴胺不足导致额叶纹状体回路异常以及5-羟色胺功能失调有关。然而Kirsch-Darrow等使用情感淡漠量表(the Apathy Scale)和贝克抑郁量表Ⅱ(Beck Depression Inventory-Ⅱ)进行验证性因子分析研究发现淡漠与抑郁可相互分离存在[18],本研究也发现12.5%的PD为单纯性淡漠,证实淡漠是可独立于抑郁存在的NMS。近期大量研究发现PD淡漠与抑郁有关[14,17,19],与本研究基本一致。Daniel等发现随着抑郁程度的增加淡漠风险也随之增加[19],而吡贝地尔可以同时改善PD淡漠和抑郁症状[20]
本研究还发现泌尿系统症状(62.5%)是常见的NMS,PD伴淡漠患者泌尿系统症状亚项及尿频及夜尿增多条目的发生率明显高于不伴淡漠患者,Logistic回归分析发现泌尿系统症状是PD淡漠的相关因素。然而目前国内外文献未见报道,具体机制尚不清楚。此外,国外研究发现PD伴淡漠患者通常是男性、年龄大、教育程度低、合并认知障碍及执行功能障碍的患者[19],临床研究还发现嗅觉减退[21]、疲劳[11]、生活质量[22]、运动症状残疾程度[14]与淡漠有关。推测不同研究存在差异可能与PD年龄、性别、种族、遗传背景、文化背景、应用不同的NMS评定量表有关。最后,本研究纳入病例较少且可能存在就诊偏倚,故结论有一定局限性,后续需对这部分患者进行随访,并纳入更多的病例以明确PD淡漠的相关因素。
综上所述,淡漠在PD常见,合并认知障碍、抑郁和泌尿系统症状的患者易发生淡漠。临床上应对淡漠提高警惕,特别是合并认知障碍、抑郁和泌尿系统症状的PD患者,需进行详细的心理评估和仔细询问病史,以期早期发现。通过认知干预和药物治疗,可以提高PD患者生活质量,改善预后。
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Outlines

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