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中医治疗轻度认知障碍的静息态功能磁共振成像研究进展
李晓陵 崔璇 佟欣 曹丹娜 彭彩亮 赵佩 范婷婷 娄睿智 吴越

Cite this article as: Li XL, Cui X, Tong X, et al. Research progress of resting-state functional magnetic resonance imaging in TCM treatment of mild cognitive impairment[J]. Chin J Magn Reson Imaging, 2022, 13(3): 122-125.本文引用格式:李晓陵, 崔璇, 佟欣, 等. 中医治疗轻度认知障碍的静息态功能磁共振成像研究进展[J]. 磁共振成像, 2022, 13(3): 122-125. DOI:10.12015/issn.1674-8034.2022.03.030.


[摘要] 中医治疗认知障碍已经取得了一定成果,但其疗效机制仍不明确。功能磁共振成像(functional magnetic resonance imaging,fMRI)是目前脑影像领域较常用的一种非损伤性活体脑功能检测技术,其中静息态功能磁共振成像(resting-state fMRI,rs-fMRI)是目前研究认知类疾病的首选方法。基于该技术发现与轻度认知障碍(mild cognitive impairment,MCI)相关的主要脑区为额叶、海马和扣带回。研究表明,中医治疗可以调控MCI患者的脑功能网络及神经环路。rs-fMRI技术可客观地评价治疗前后受试者脑区功能连通性和局部脑区活动指标,了解中医治疗脑效应机制,为探讨神经系统疾病的中医疗效提供新思路和新方法。
[Abstract] Traditional Chinese medicine (TCM) has made some achievements in the treatment of cognitive impairment, but its therapeutic mechanism is still unclear. Functional magnetic resonance imaging (fMRI) is a commonly used noninvasive in vivo brain function detection technology in the field of brain imaging, and resting-state fMRI (rs-fMRI) is also the preferred method for the study of cognitive disorders. Based on this technology, it is found that the main brain areas related to mild cognitive impairment (MCI) are the frontal lobe, hippocampus and cingulate gyrus. Studies have shown that TCM treatment can regulate the brain function network and neural circuits of MCI. The rs-fMRI technology was used to objectively evaluate the functional connectivity and activity indicators of local brain regions of subjects before and after treatment, to understand the brain effect mechanism of TCM treatment, and to provide new ideas and methods for exploring the therapeutic mechanism of TCM treatment of neurological diseases.
[关键词] 轻度认知障碍;静息态功能磁共振成像;针刺;导引功法;中医
[Keywords] mild cognitive impairment;resting-state functional magnetic resonance imaging;acupuncture;Daoyin exercises;traditional Chinese medicine

李晓陵 1   崔璇 2   佟欣 2   曹丹娜 1   彭彩亮 1, 2*   赵佩 2   范婷婷 2   娄睿智 2   吴越 2  

1 黑龙江中医药大学附属第一医院CT磁共振科,哈尔滨 150040

2 黑龙江中医药大学研究生院,哈尔滨 150040

彭彩亮,E-mail:p18804618528@163.com

作者利益冲突声明:全体作者均声明无利益冲突。


基金项目: 国家自然科学基金面上项目 82074537,81373714 黑龙江省自然科学基金项目 LH2021H101,LH2020H103 哈尔滨市科技创新人才优秀学科带头人基金项目 2016RAXYJ096 哈尔滨市科技创新人才青年后备基金项目 2017RAQXJ180 黑龙江中医药大学科研基金项目 2019MS03
收稿日期:2021-11-10
接受日期:2022-02-17
中图分类号:R445.2  R749.1 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.03.030
本文引用格式:李晓陵, 崔璇, 佟欣, 等. 中医治疗轻度认知障碍的静息态功能磁共振成像研究进展[J]. 磁共振成像, 2022, 13(3): 122-125. DOI:10.12015/issn.1674-8034.2022.03.030

       轻度认知障碍主要特点是记忆力或其他认知功能轻度受损,日常生活能力降低[1]。随着我国人口老龄化程度持续增加,对医疗带来更严峻的挑战,其中最典型疾病是阿尔茨海默病(Alzheimer′s Disease,AD)的高发[2]。由此产生的医学和社会学双重问题,引起国内外学者的高度重视。然而,迄今为止痴呆尚无根治疗法,如何对AD早期阶段的轻度认知障碍(mild cognitive impairment,MCI)给予有效干预,受到业内专家的持续关注[3, 4, 5]

       随着医学技术的日新月异,脑影像方法已成为研究精神障碍机制的重要工具。静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)技术发展于上世纪90年代,作为一种活体脑功能成像方式,可通过观测大脑区域变化,对采集数据进行分析处理,在一定程度上反映各脑区之间的相互作用和神经网络连接,因此极大地促进了神经疾病研究的进展,为MCI分析提出新方法[6]。rs-fMRI操作简单、扫描用时短,可在非外界刺激状态下检测脑神经活动,且受试者无需做出反应[7]

       从脑部能量代谢与神经元活性关系方面研究脑功能神经网络的异常改变,对观察不同脑区间相互联系和探测脑的自发活动具有重大贡献[8]。rs-fMRI主要包括局部一致性(regional homogeneity,ReHo)、低频振幅(amplitude of low-frequency fluctuation,ALFF)、功能连接(functional connectivity,FC)等方法,这些方法不仅可以观察脑区内部神经元活性和其同步性,还可以对脑区之间的功能联系进行研究,也是最广泛、最经常用来评估认知类疾病临床疗效的手段[9]

       中医在认知障碍治疗方面具有多靶点、全方位、辨证论治等独特优势,已经取得了丰硕成果[10]。有研究者采用针刺、中药、中西医联合等方式治疗MCI,并收到较好的临床效果,但是中医治疗该病的靶标及疗效机制仍不明确[11, 12, 13]。本文对近年来国内外采用rs-fMRI技术探索中医治疗MCI的研究进行综述。

1 针刺治疗MCI效应机制rs-fMRI研究进展

       现在已有大量研究证实手针、电针、针药结合等方式的治疗,对认知障碍均有明显疗效[14, 15, 16]。针刺治疗过程中研究者选穴的标准各有不同,多以任脉、督脉、足阳明胃经、足厥阴肝经和足少阴肾经等经络腧穴为主[17, 18]。研究者主要采用ALFF分析、ReHo分析或FC分析等方法,探讨针刺治疗认知障碍疾病的效应机制。

1.1 针刺治疗MCI脑区ALFF效应

       Jia等[19]采用rs-fMRI技术研究针刺太溪穴后的脑区变化,和健康者比较发现太溪可引起MCI患者额叶、顶叶和颞叶ALFF值的变化。通过分析数据可以认为针刺治疗后患者左额叶内侧回ALFF值明显增加,右颞下回和后扣带回ALFF值明显降低,对MCI患者脑区神经元活动的影响比健康对照组更为显著。Zhang等[20]研究针刺内关穴对血氧水平依赖信号中低频振荡率的影响,发现刺激内关可以升高双侧额上回、右侧楔前叶等区域ALFF值,相应皮层功能也与中医所认为的内关穴主治相契合。因此,可以认为刺激内关是提升认知能力的有效方法。王丰等[21]发现MCI患者取双侧太冲、神门等穴,针刺前后同时进行简易精神状态量表(Mini-mental State Examination,MMSE)和蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)比较,两种神经心理学量表测试评分差异均具有统计学意义,针刺后得分明显升高。与针刺前比较,治疗后MCI患者左侧前扣带回、左侧丘脑、右侧岛叶、右侧海马旁回的ALFF值增高;ALFF值减低的脑区则主要集中在小脑后叶、额下回、枕下回等区域。以上结果证明,针刺太溪、内关等穴位可以增强额叶、顶叶等与认知功能相关脑区的神经元活动,ALFF值变化表明针刺治疗MCI可通过双向调节额上回、海马旁回、扣带回等多个脑区的神经元活动而产生疗效,提升患者认知能力,为深入研究针刺穴位精准治疗MCI提供支持。

1.2 针刺治疗MCI脑区ReHo效应

       Huang等[22]探讨MCI患者和健康者对针刺的脑反应,采用非重复相关事件rs-fMRI设计范式,发现在静息状态下MCI患者中央前回、额上回和脑岛的ReHo值较健康对照组升高,而颞中回、海马旁回和扣带回皮层的ReHo值降低。此外,针刺后MCI患者的楔前叶和扣带皮层区域均出现ReHo值升高,但健康对照组在后额叶内侧回、前扣带回和脑岛等区域ReHo值则明显下降。表明针刺对MCI患者症状改善的干预机制还需进一步研究。郑运松等[23]探讨嗅三针——针刺双侧迎香穴和印堂穴对患者认知状态的治疗效果,发现认知功能有显著改善,表现为前额叶、海马、扣带回ReHo值升高,颞中回、角回、缘上回ReHo值减低,嗅三针组主要改变中央执行网络和默认网络脑区的ReHo值。总之,不同针刺配穴方法均对MCI患者额叶、海马、扣带回ReHo值产生作用,可能是通过调节脑网络达到改善认知功能的目的,rs-fMRI技术为中医针刺疗法提供了客观评价途径。

1.3 针刺治疗MCI脑FC效应

       FC可反映不相邻脑区神经元活动的相关性或解释单一脑区和其他脑组织间的相互关系。Chen等[24] 依据太溪穴不同针刺深度对MCI患者和健康人的脑网络功能连通性进行分析。深刺太溪穴使MCI患者背外侧前额叶皮层和海马体以FC为中央枢纽形式出现,可见深刺太溪与脑区激活之间存在相关性;在浅刺状态下,MCI患者只有个别脑区显示出连通性,而健康组明显关联的脑区更少。可以认为生理和病理认知状态下针刺深浅度会使FC出现不同连接形式,MCI患者深刺太溪可以诱导更强的FC。Liu等[25]在研究中也发现MCI患者在深刺太溪穴后,与记忆功能相关FC出现显著变化。由此得出,针刺深部肌肉层可能是实现临床效果的关键。中医针刺治则强调不同人群在接受治疗时需因人而异选择针刺深度,rs-fMRI技术有助于探讨深刺太溪穴治疗MCI的FC机制,进而引出下一步研究方向。

2 其他中医疗法对MCI效应机制rs-fMRI研究进展

2.1 导引功法治疗MCI的rs-fMRI效应

       导引功法对认知类疾病的相关研究,吸引国内外诸多学者的关注。有研究表明ALFF值在右侧海马和双侧扣带回前皮质的变化与MoCA评分变化显著相关[26, 27, 28]。Tao等[29]将69例MCI患者随机分为八段锦组、快步行走组和对照组,对照组只进行无运动健康教育。经24周治疗后,研究显示八段锦组与快步行走组比较,右侧海马ALFF值明显降低;八段锦组相比对照组可见双侧扣带回前皮质功能区ALFF值增加,并且八段锦组海马与右角回之间的FC值与对照组相比也有所增加。同时八段锦组在左内侧、背侧额叶皮质和右侧海马存在显著激活。MoCA评分和ALFF值变化可以证明八段锦具有改善MCI患者认知能力的作用。Tao等[30]选取双背外侧前额叶皮层为种子点进行连接性分析,研究比较太极拳和八段锦对老年人认知控制网络功能和FC的变化。两试验组分别练习太极拳、八段锦12周,对照组仅接受基本健康教育。结果发现与对照组相比,两试验组精神控制功能明显改善。太极拳组显示与左额上回之间的连接性显著降低;八段锦组背侧额前皮质、壳核和岛叶之间的连接明显减少。由此,发现中医传统导引功法能够对海马、额叶皮质等MCI相关脑区产生作用,可作为防治认知衰退的有效方法,提示了导引功法对治疗认知类疾病的作用。

2.2 中药治疗MCI的rs-fMRI效应

       有研究表明中药方剂能够提升患者认知功能[31, 32, 33]。Zhang等[34]在观察复方补肾胶囊治疗MCI的长期疗效时发现,治疗组记忆、语言和执行功能均得到改善;rs-fMRI结果显示,治疗组右楔前叶和默认网络连通性FC值持续增加;安慰剂组的连通性FC值降低。重要的是该指标变化与治疗组24个月后行MMSE评分和记忆分数评分的变化呈正相关。说明中药复方补肾胶囊治疗MCI可以改善多个认知领域功能,增加默认网络局部和全脑的连通性。此项研究的前期报道中记述,加味四逆散、小柴胡汤等中药复方治疗认知障碍疗效显著,不良反应较少[35]。由此,长期运用中药治疗MCI,能够改善患者认知能力,延缓认知衰退,减少AD的发生[36, 37]。但目前基于rs-fMRI技术对中药治疗认知障碍类疾病疗效机制的深入研究甚少[38, 39],所以应用rs-fMRI技术探寻中药治疗MCI具有很高的临床意义。

3 小结与展望

       针刺、导引功法、中药治疗MCI,在rs-fMRI技术下将采集到的指标ALFF、ReHo、FC作为神经影像学的生物标志物,其数值变化体现中医方法对相关的脑结构核团如额叶、海马、扣带回等产生了调节作用,且这些脑区涉及认知功能、情绪加工与学习记忆[40]。鉴于中医疗法在MCI患者治疗中的作用,结合rs-fMRI影像技术进行纵向研究,可直观、系统地阐明脑网络复杂的功能变化,为明确腧穴针刺方法与脑效应机制存在关联性打下基础,说明针刺、导引功法和中药是治疗MCI的有效方法。其他中医疗法如耳针、电针、穴位埋线等均有关于MCI临床治疗的文献记载,但未见进行rs-fMRI研究的报道[41, 42]。今后的研究中,我们可以应用rs-fMRI技术比较分析不同人群和临床症状所对应的中医优势诊疗路径,完善中医治疗标准化方案;建立大样本、多中心的中医学影像研究共享模式。结合人工智能、深度学习技术,控制完善试验干扰因素的参数设计,优化试验方案,推动开展中医治疗MCI的精准影像学研究。

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