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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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Chinese Journal of Alzheimer's Disease and Related Disorders >

2019 , Vol. 2 >Issue 4: 499 - 503

DOI: https://doi.org/10.3969/j.issn.2096-5516.2019.04.007

Dementia with Lewy bodies: a reappraisal of the clinical features in a series of 30 cases

  • JIN Hong 1 ,
  • WANG Hongquan 2 ,
  • LI Yanfeng , 3
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  • 1 Department of Neurology, Beijing nuclear industry hospital, People’s Republic of China
  • 2 Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, People’s Republic of China
  • 3 Department of Neurology, Peking Union Medical College Hospital

Received date: 2019-08-11

  Revised date: 2019-08-18

  Online published: 2019-12-25

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Abstract

Objective: To review the clinical features at presentation and their association with treatment in detail in outpatients with dementia with Lewy bodies (DLB). Methods: Thirty outpatients were enrolled retrospectively from Department of Neurology of Peking Union Medical College Hospital from January 2012 to September 2019 were enrolled when they met the clinical criteria of probable DLB. The clinical features at presentation and their association with treatment in detail were reviewed and analyzed. Baseline demographics, presenting clinical and behavioural and psychological symptoms of dementia, functional and cognitive assessment scores, and complications during follow-up were reviewed. Results: There were 24 men and 6 women, and their mean age was (71.3±7.8) years. The mean duration from memory impairment to presence of Parkinsonism was less than 1 year. Memory impairment (100%),sleep disorder (100%),parkinsonism (90%),constipation (73%),and visual hallucination (70%) were the major symptoms. Other clinical features includes frequent nocturia (50%),restless legs (13%),recurrent falls or syncope (20%). Rapid eye movement sleep behavior disorder (RBD) and anxiety were present at 1~10 years prior to DLB onset in 17 and 20 patients, respectively. The symptoms of parkinsonism includes tremor, rigidity, bradykinesia, and postural instability. Neuroimage examination shows MAT grading of hippocampus I (47%)、II (47%)、III (6.7%). PET showed the cingulate island sign in three patients. Memantine or cholinesterase inhibitors could improve cognitive impairment, visual hallucination, and behavioral symptoms in a large majority of patients. L-DOPA or dopamine receptor agonists lightly improve parkinsonism. Sertraline or citalopram acetoacetate (50%) can alleviate mood disorders and sleep disturbance. Quetiapine (13%) can mitigate nocturnal delirium. Clonazepam (57%) decrease the onset of RBD. Conclusion: Anxiety and RBD may be present before the onset of DLB. The incidence of memory impairment, sleep disorder, visual hallucination, and bradykinesia were high. These symptoms can be mitigated by started on specialized drugs for the symptomatic treatment.

Key words： Dementia with Lewy bodies; Clinical features; Treatment

Cite this article

JIN Hong , WANG Hongquan , LI Yanfeng . Dementia with Lewy bodies: a reappraisal of the clinical features in a series of 30 cases[J]. Chinese Journal of Alzheimer's Disease and Related Disorders, 2019 , 2(4) : 499 -503 . DOI: 10.3969/j.issn.2096-5516.2019.04.007

路易体痴呆（dementia with Lewy bodies, DLB）是原发性变性病痴呆的第2位常见病因,仅次于阿尔茨海默病痴呆[1]。其主要临床表现为波动性认知功能障碍,视幻觉,帕金森病运动症状及快速动眼时期睡眠行为障碍[2]。由于该病在早期临床表现较多,常常不易与其它痴呆类疾病如阿尔茨海默病,或者运动障碍疾病如帕金森病相鉴别[3],因而许多患者因为延误诊而得不到及时和恰当的治疗[4]。本研究总结本院门诊诊断的DLB的临床特点及诊治经验,期待为提高临床医生对于该病的识别率以及选择正确的治疗提供有益的参考。

1 对象与方法

1.1 对象

2012年1月至2019年9月协和医院神经科痴呆和帕金森门诊诊断为DLB患者,筛选出符合极有可能诊断（probably）的患者。

1.2 研究方法

1.2.1 一般资料收集

录入患者的年龄、性别、文化程度、神经系统查体及随访。

1.2.2 诊断标准

DLB诊治中国专家共识（2015）及国际专家共识（2017）的非常有可能标准,即：认知损害影响到患者的日常生活能力即痴呆（必要特征）,并具备2个以上核心特征：波动性认知障碍、视幻觉、帕金森的运动症状及快速动眼期睡眠障碍（rapid eye movement sleep behavior disorder, RBD）。如果仅有一个核心特征,则需要一个及以上提示性生物标志物：(polyethylene terephthalate, PET)或(Single-Photon Emission Computed Tomography, SPECT)提示有基底节多巴胺转运体下降,心肌显像显示(metaiodoenzylguanidine, MIBG)摄取下降或者多导睡眠图显示Rapid (Eye Movement, REM)期无失肌张力（without atonia）。

1.2.3 认知功能检查

包括(Montreal cognitive assessment, MMSE)及(Mini-mental state examination, MoCA)检查。

2 结果

2.1 一般情况

共有30例患者符合DLB诊断,平均年龄(71.3±7.8)岁,男24例,女6例,文化程度大学8例,高中15例,初中6例,小学1例;其中高血压病史者17例,糖尿病史者20例。从发病到临床诊断时间为半年至2年,最长随访时间为6年。痴呆门诊就诊诊断的为10例,帕金森门诊就诊诊断的为20例。所有患者均进行了MRI检查,其中10例做了PET-CT检查;APOE基因分析有两例携带Ɛ4,均为Ɛ3 Ɛ4分布型,所有患者痴呆和运动症状相继出现时间不超过1年。

2.2 临床特点

2.2.1 认知下降（100%）

所有患者均有认知下降,MMSE检查结果为 （21.4±5.6）分,MoCA为 （17.6±6.5）分,分项检查显示有近记忆下降为17例,视空间障碍为20例,执行能力下降17例。

2.2.2 睡眠障碍

存在白天过度睡眠（EDS）为27例,出现RBD 17例,其中发病前2年、5年和10年出现RBD的患者分别为6例、10例和8例。夜尿次数多（> 3次）15例,不安腿4例。

2.2.3 视幻觉

17例患者存在视幻觉,多于夜间或视线不佳时出现,起病初期为视错觉,渐发展至视幻觉,内容包括有猫、狗、蛇等动物,或故去的人等。

2.2.4 帕金森运动症状

主要指震颤、强直、迟缓或姿势异常,27例（90%）患者存在帕金森运动症状,其中具备2个以上症状的有10例,具备1个17例,其中以迟缓最为常见,HY分级在1~3.5。

2.2.5 焦虑或其他情绪障碍病史

20例（67%）存在,其中发病前10年出现焦虑或其它情绪障碍病史者为4例、5年出现者为6例、近2年出现者为4例。反复跌倒或晕厥6例,便秘22例。无患者报告出现精神药物过敏。

2.2.6 实验室检查

所有患者均进行了头颅MRI 检查：存在多发腔隙梗死为20例（67%）,头颅MRI显示海马MAT分级如下：I级14例（47%）,II级14例（47%）,III级2例（6.7%）,3例患者PET检查有扣带回岛症。

2.2.7 治疗效果

2.2.7.1 认知障碍治疗

共有20例患者接受美金刚或艾斯能治疗,治疗后MoCA和MMSE均有改善。视幻觉或夜间谵妄明显改善14例（70%）,症状改善维持一年以上者10例（50%）,半年以上6例（30%）,无效4例（20%）例。23例患者服用左旋多巴或受体激动剂治疗半年以上,均报告可轻度改善帕金森症状。

2.2.7.2 情绪障碍、夜间谵妄治疗

共有15例患者服用舍曲林或西酞普兰,对于情绪障碍控制满意,并能改善睡眠障碍。4例夜间谵妄患者服用奎硫平25~50 mg,能控制症状。

2.2.7.3 RBD的治疗

17例患者服用氯硝西泮0.5~2 mg,能够减轻症状。

3 讨论

1914年德国医生Frederick Lewy发现原发性帕金森病患者中脑黑质细胞内存在一种胞浆内包涵体,后被命名为路易体（Lewy body, LB）,并证实为帕金森病的病理基础[5]。以后的研究证实路易包涵体的主要成份是α突触核蛋白,该蛋白因基因或者环境因素而改变其生理结构,形成不溶的淀粉样结构,最后形成包涵体,产生神经系统毒性作用而致神经细胞变性坏死。1960年以后病理研究发现在一些痴呆患者的新皮层内也发现有LB,美国的尸解结果显示这一类患者约占痴呆总数的10%~20%。1985年由Mckeith组织专家形成DLB诊断和治疗国际专家共识,并于2017进行更新。
新版的共识把RBD加入为核心症状[2,6],提高了其在诊断DLB的地位,同时增加了PET]、心脏MIBG以及多导睡眠纪录仪异常等作为提示性生物标志物,这种改变能够让DLB的诊断有了客观指标,是新技术带来的进步[7⇓⇓⇓⇓-12]。
本文对30例DLB患者进行总结,所有患者均表现有认知功能下降并影响到日常生活,认知障碍的模式以视空间和执行功能较为突出。在诊断共识中提到的波动性[2],很难以与白天的过度嗜睡鉴别,笔者认同以过度嗜睡作为波动性的描述。视幻觉也是较为常见的症状,本组患者也多数存在,而且在夜间更为明显,并且常常由早期视错觉发展至视幻觉,反映了患者的枕叶皮质代谢受累过程。
帕金森病的运动症状是诊断DLB的重要指标[2],早期诊断的患者,帕金森病运动症状并不严重,本组30患者HY分级偏轻说明了这个问题,也说明了DLB患者的神经细胞受累的主要部位是皮质,而不是帕金森病患者的黑质。
本组30例患者RBD发生率较高,其中不少患者在出现认知症状之前许多年就已存在,也有人将RBD视为路易体谱系病的重要症状,属于路易体睡眠障碍的重要表现[13]。其中有一例患者在认知症状出现前10年以上就有RBD,因此,RBD可能作为DLB或帕金森病的早期症状应予以重视[13⇓⇓-16]。
DLB的疾病过程缺乏流行病学资料,一般认为其病程介于阿尔茨海默病和帕金森病程之间,病程相对较长,由于其临床表现具有异质性和多样化,治疗上应采用慢病管理及个体化策略[17],针对不同的临床症状给予相应的处理,一般来说患者的认知障碍、视幻觉可以通过给予目前治疗痴呆的药物进行治疗,可获得有效改善,特别是美金刚既有神经细胞保护[18]作用,又可增强记忆,且对胆碱能神经元没有影响,因此对于此类老年患者相对安全,也有较好的效果,由于本组患者例数较少,需要大规模临床观察来进一步证实其疗效。患者常常出现的情绪障碍或其它精神行为症状在处理上应小心,避免使用传统的抗精神病药物。
提高DLB的识别率是临床医生重要责任,本组30例患者分别在痴呆和帕金森病门诊中得以诊断,因此建议痴呆门诊中加强对帕金森运动症状的识别,而帕金森门诊中也要重视认知功能的评估,让更多患者得到早期诊断及适当的治疗。

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