轻度认知障碍(专业版)
轻度认知障碍(MCI)是介于正常衰老和痴呆之间的一种中间状态,表现为温和的、反复的记忆衰减,及语言、思维和判断等功能障碍症候群。
定义
轻度认知障碍(MCI)是介于正常衰老和痴呆之间的一种中间状态,表现为温和的、反复的记忆衰减,及语言、思维和判断等功能障碍症候群。虽然65岁以上的人患痴呆症和阿尔茨海默氏症有更高的几率,然而,许多曾经患有轻度认知障碍的人未必将患这些疾病,有的甚至恢复正常。病因
MCI没有单一原因,正如这种疾病没有单一结果一样。MCI的症状可能多年保持稳定,或进展到阿尔茨海默氏病或其他类型的痴呆症,或随着时间推移而改善。年龄增长过程深刻地影响着大脑,如神经元和线粒体膜的退化,引起脑功能下降。长期的氧化应激、突破进入脑屏障的炎性因子,激素水平下降(大脑激素受体密度最大),脑血管不同程度地形成栓塞以及营养不良等,均可影响记忆功能。
导致MCI的原因包括:
- β淀粉样蛋白异常凝块(斑块)和Tau特征的阿尔茨海默病微细蛋白质团块(缠结)。
- 路易体,与帕金森氏病有关的另一种蛋白质的微细结块,路易体痴呆和某些阿尔茨海默病。
- 脑血管梗塞(小中风)或脑血流量减少。
- 海马体萎缩,这是一个对记忆很重要的大脑区域。
- 大脑充满液体的空间(脑室)扩大。
- 主要大脑区域使用葡萄糖减少,它是脑细胞能量的最主要来源。
风险因素
可能增加患MCI几率的因素包括:- 痴呆家族史、老年痴呆症。
- 健康状况,如“三高”、高同型半胱氨酸血症、脑梗塞、脑损伤等。
- 慢性压力
- 抑郁、焦虑。
- 缺乏体力活动。
- 用药过度。
- 药品依赖症。
- 吸烟。
- 缺乏社会接触、交流。
- 受教育水平低。
- 营养不良和缺乏维生素。
- 曝露于环境毒素中。
症状
主要症状是频繁、持续的丧失记忆力、思维和判断力下降,超出了正常年龄的预期,表现如:- 对刚读到或看到东西,能记忆的越来越少。
- 需要更长的时间来回忆信息。
- 忘记约会或社交活动等重要事件。
- 开始难以找到熟悉环境的方法。
- 变得更加冲动或表现出越来越差的判断力。
- 情绪抑郁
- 脾气暴躁、攻击性
- 焦虑
- 冷漠
并发症
MCI患者发展为痴呆症的风险显著增加。一般而言,大约有1%至2%的老年人患有痴呆症。而在MCI的群体中,约有10%至15%可发展为痴呆症。疗法
综合选项包括如下调整饮食与生活方式
- 健康饮食,富含优质蛋白、深海鱼和坚果,及新鲜蔬菜、水果
- 限制热量摄入,但须满足维生素和矿素物质等营养素
- 适度饮酒
- 不抽烟,或戒烟
- 积极参与社交活动、智力游戏等
- 定期运动锻炼,尤其是各种有氧运动
- 保持健康体重
营养与草本综合干预
以下是基于循证医学和营养学有关文献综合的结果。
- 银杏叶:可能是研究最广泛、最常用的支持认知功能的综合疗法。银杏提取物已被证明可以减少氧化应激、减少神经炎症、改善微循环、调节神经递质活性和促进神经可塑性1。动物研究表明,银杏可能刺激神经干细胞增殖和活性2。
- 假马齿苋:一种在印度具有宗教、文化和医学重要性的植物,在阿育吠陀医学中已经使用了数百年5。在临床前研究中,假马齿苋提取物已被证明具有降低大脑氧化应激、调节神经递质活性、减少β-淀粉样蛋白沉积、加强神经元连接以及增加脑血流量等6。人类研究表明,假马齿苋也可能改善应激反应7。此外,在小鼠中,假马齿苋提取物增加了大脑中脑源性神经营养因子(BDNF)的水平和新神经元的产生8。
- 石杉碱甲:已被证明能抑制乙酰胆碱酯酶。乙酰胆碱是自主神经系统中的一种主要神经递质,其被乙酰胆碱酯酶加速分解会导致与年龄相关的认知能力下降和痴呆13。一些抗痴呆药物如多奈哌齐,也通过抑制乙酰胆碱酯酶发挥作用。此外,临床前证据表明,石杉碱甲可以减少氧化应激,防止β-淀粉样蛋白和磷酸化tau积累,支持线粒体功能,并增加大脑中神经生长因子的产生14。
需要注意的是,服用石杉碱甲可能存在轻微的副作用,如消化不良和便秘、头晕、心率减慢和口干15。
- 乙酰L肉碱:在线粒体中产生并参与细胞能量生产,而且是乙酰胆碱形成的前体分子18。一项研究报告称,从没有认知问题到主观记忆障碍,再到轻度认知功能障碍,再到痴呆,受试者的血清乙酰L肉碱水平逐渐降低19。临床前研究表明,乙酰L肉碱可以保护脑线粒体功能,减少氧化应激,通过小胶质细胞抑制炎症活性,并改善神经系统中的多巴胺信号传导20。
- 多酚类:多酚是一类在植物中发现的强氧化应激降低化合物。在652名65岁及以上无痴呆症的受试者中,尿液中多酚含量较高,表明多酚摄入量较高,三年监测表明认知功能下降少25。此外,在认知功能的某些方面测试中,摄入特定的富含多酚的食物(橄榄油、咖啡、核桃和葡萄酒)与更好的认知表现独立相关26。
- 欧米伽3脂肪酸:DHA(二十二碳六烯酸)是大脑健康的关键营养素,缺乏DHA会导致情绪不佳和认知功能障碍等症状;它在神经元细胞膜中的浓度很高,在维持膜流动性方面发挥着重要的结构作用53。临床前研究表明,DHA加上EPA可以预防淀粉样斑块和神经原纤维缠结54,以及防止脑内小血管堵塞和改善血液流动55。大脑中B族维生素的正确使用也可能需要充足的ω-3脂肪酸状态56。此外,DHA具有抗炎作用,是神经保护素D1的前体,D1是一种参与神经元生长和存活的信号分子53。
- 维生素B族:同型半胱氨酸代谢需要B族维生素,而B族维生素水平较低,特别是叶酸、维生素B12和维生素B6,与高血同水平和老年人更大的认知能力下降有关。虽然B族维生素可降低高血同,不过,临床试验结果在认知益处方面参差不齐67,68。
- 甘磷酰胆碱(α-GPC):它是磷脂酰胆碱的半合成衍生物,也是神经递质乙酰胆碱的前体。乙酰胆碱是自主神经系统中的一种主要神经递质,其加速分解可能导致与年龄相关的认知能力下降和痴呆76。事实上,在“超级老年人”(即具有异常年轻认知功能的老年人)的大脑中,已经观察到乙酰胆碱代谢酶(乙酰胆碱酯酶)的浓度降低77。
- 丝氨酸磷脂:大脑中含有高浓度的磷脂酰丝氨酸,构成细胞膜和髓鞘的一部分。磷脂酰丝氨酸对认知功能的各个方面以及神经系统对运动功能的控制都是必要的。衰老与大脑结构和化学物质的恶化有关,而脑结构和化学成分的恶化可能受到磷脂酰丝氨酸补充的影响82。
- 苏糖酸镁:它被发现在提高脑镁水平方面尤其有效88。脑镁水平的升高增强了研究动物的神经可塑性和改善了认知功能89。补充苏糖酸镁已被证明可以防止特定神经递质受体(NMDA受体亚基NR2B)与年龄相关的减少,在衰老和阿尔茨海默病的动物模型中,可抑制炎症信号传导、减少淀粉样斑块的形成,保护神经连接和防止记忆丧失90。其他动物研究表明,苏糖酸镁可能会增强阿尔茨海默病样脑病小鼠的精神和身体刺激活动的认知增强作用91。
- 吡咯喹啉醌(PQQ):一种支持生长和发育的重要化合物,在氧化还原生物化学反应中发挥着关键作用92。临床前研究表明,提高PQQ水平可以改善线粒体数量和功能,减少全身和大脑炎症,延长细胞寿命,防止神经毒素,并可能改善神经和心血管健康93,94。多项研究还表明,PQQ可以防止β-淀粉样蛋白的积累95。此外,已经发现PQQ可以刺激一种名为神经生长因子的蛋白质产生96,促进神经细胞的再生97,并保持实验动物的认知功能98。
- 辅酶Q10:辅酶q10已证明其神经保护作用可能是通过增强线粒体功能和调节小胶质细胞(介导神经炎症的大脑免疫细胞)介导的101。低血清辅酶Q10与老年人致残性痴呆的风险增加和心力衰竭患者认知功能恶化有关102,103。临床前证据表明辅酶Q10可以减缓神经退行性疾病如亨廷顿、帕金森和阿尔茨海默病患者的认知能力下降104。长期(1至2年)每天摄入100-150mg辅酶Q10泛醇已被证明可以改善日本各年龄段人群的认知表现105。
- 类胡萝卜素:包括叶黄素和玉米黄质、β胡萝卜素、番茄红素和虾青素等。在人类食用的水果和蔬菜中发现了大约50种不同类型的类胡萝卜素,在人体组织和血液中发现了约20种类胡萝卜素106。血清和视网膜中叶黄素和玉米黄质浓度较高与炎症的几种生物标志物以及认知和神经传递测量的改善有关;类胡萝卜素保护细胞免受氧化应激,从而可能通过防止神经元细胞损伤来减缓认知能力下降;类胡萝卜素还被证明可以通过降低细胞因子和其他促炎分子的循环水平来减少炎症信号106。神经成像研究表明,叶黄素和玉米黄质浓度较高的老年人脑白质完整性增加107。
- 维生素D:尽管维生素D一般与骨骼和免疫健康有关,但它在中枢神经系统中也发挥着重要作用。影响细胞功能和基因表达的维生素D受体几乎存在于身体的每一个细胞上,包括中枢神经系统的细胞(如神经元、星形胶质细胞和小胶质细胞)。其中一些细胞可以合成生物活性形式的维生素D(1,25-二羟基维生素D),这表明活性形式在中枢神经系统中很重要115。
- 维生素K2:“维生素K2”是指一组至少15种相关的化合物,称为甲萘醌(MKs)。在甲萘醌中,MK-4和MK-7与年龄相关的认知功能变化有关119。例如,在一项对365名老年参与者进行的研究中,大脑中MK-4浓度越高,患MCI的风险可低达17-20%120。
- 芒果叶提取物:已在传统医学实践中用于一般健康和治疗疲劳127。在临床前研究中,芒果叶提取物已被证明具有抗炎和神经保护特性,这些积极作用主要归因于芒果苷(Mangiferin),其所含的一种多酚128。芒果苷似乎是儿茶酚-O-甲基转移酶(COMT)的抑制剂,COMT负责分解神经递质如多巴胺、肾上腺素和去甲肾上腺素127。动物研究表明,芒果苷改善了认知的几个方面,包括空间识别和短期和长期记忆129。
- 长春西汀:长春西汀已证明具有神经保护作用,如改变炎症信号、减少氧化应激、改善细胞能量产生、抑制血管壁增厚、扩张脑血管,并可能防止动脉粥样硬化斑块形成130,131。在一项针对26名经历过多次中风的患者的安慰剂对照试验中,在三个月后的一次认知功能测试中,长春西汀防止了认知功能恶化132。其他使用口服长春西汀的研究表明,它能够改善轻度认知障碍和脑血管功能不全患者的认知能力133。注意:怀孕或可能怀孕的妇女不宜服用长春西汀。
- 锂:锂是一种在临床上高剂量用于情绪稳定剂的矿物,主要针对双相情感障碍患者134,135。有些地区的饮用水中天然存在微量锂,在人群研究中,饮用水中锂的含量较高与痴呆和精神疾病的发病率较低有关136。越来越多的临床前证据表明,锂可能通过其预防氧化和炎症神经元损伤、增强神经可塑性、调节蛋白质代谢、控制生理节律和下丘脑-垂体-肾上腺(HPA)轴活性134,137。此外,动物和实验室研究表明,长期低剂量锂治疗可以增加BDNF的神经元产生138。在易患阿尔茨海默病的大鼠中显示出小剂量锂可以减少氧化应激、神经炎症和异常蛋白质积累,以及促进神经元再生和防止记忆丧失139。
- 可可:含有高浓度的多酚/黄烷醇抗氧化剂。可可及其黄烷醇可以改善血管功能,促进脑血液循环和改善认知功能143。实验研究表明,可可能抑制β-定粉样蛋白的聚集144。此外,可可的咖啡因、儿茶素和其他成分可能有助于其对大脑健康的益处145。黑色巧克力富含可可多酚。
- 野燕麦:野生绿燕麦(Avena sativa)的提取物可抑制一种名为单胺氧化酶-B(MAO-B)的酶150。代谢多巴胺的MAO-B活性随着年龄的增长而增加,降低多巴胺水平,可能导致氧化应激和线粒体功能障碍,加速组织老化151。阻断MAO-B有助于使多巴胺水平正常化,并可以减少氧化应激,改善认知和记忆152。野燕麦提取物还能扩张脑血管,抑制磷酸二酯酶-4153,这种作用可以减缓与年龄相关的认知能力下降154。
- 猴头菇:又称狮鬃菇,一种历史悠久的药用菇。其提取物已被证明具有抗炎、降低氧化应激作用,据报道,食用猴头菇与神经保护、促认知、抗衰老和抗抑郁等健康益处有关158。在一项针对30名患有轻度认知障碍的老年人的随机对照试验中,与安慰剂相比,每天服用3000 mg狮鬃菇粉治疗16周可改善认知功能159。在动物研究中,狮鬃菇增强了健康野生型小鼠的神经元功能并改善了记忆能力160。还发现狮鬃菇提取物可刺激神经元生长因子和新神经元的形成,以及在阿尔茨海默病小鼠模型中减少β-淀粉样蛋白斑块和淀粉样蛋白诱导的炎症161。
- 鼠尾草:自古以来就因其药食同源特性而闻名。近年来,鼠尾草增强认知能力而引起关注162。在阿尔茨海默病动物模型中,鼠尾草提取物已显示出抑制乙酰胆碱酯酶活性和防止外周BDNF水平下降的作用,在阿尔茨海默病或轻度认知障碍患者中BDNF往往会减少163,164。鼠尾草的提取物和生物活性化合物被证明具有一些抗炎作用162。
- 南非醉茄:阿育吠陀医学重要的草药之一。它含有抗氧化、抗炎和免疫刺激特性的生物活性化合物169。细胞和动物模型研究表明,南非醉茄提取物和相关化合物通过多种信号通路拯救神经元细胞免受化学损伤和炎症,保护神经元免受阿尔茨海默病、帕金森病和亨廷顿舞蹈症等典型疾病的神经退行性过程的影响170。
- 孕烯醇酮:一种类固醇激素,在肾上腺、大脑和其他器官中由胆固醇合成。孕烯醇酮既可以自身调节信号通路,也可以进一步代谢形成其他类固醇激素,包括孕酮、醛固酮、皮质醇和睾酮。在大脑中,孕烯醇酮已被证明可以调节NMDA受体介导的神经传递,从而支持学习和记忆174。此外,孕烯醇酮具有抗炎特性175。
- 雷公根(积雪草):含有高浓度的几种有益营养物质,包括三萜、类胡萝卜素、维生素B和C、矿物质和其他植物营养素等。其所含的关键活性成分之一是积雪草酸(Asiatic acid),临床前研究表明,它可以预防某些药物引起的认知能力下降,还可以调节神经传递,以及其他有益的认知和神经作用180。许多积雪草制剂被标准化为积雪草苷,积雪草苷在体内代谢为积雪草酸181。
- 碧萝芷:一种法国海松皮提取物,具有强大的抗炎和抗氧化特性,支持认知功能和精神表现。碧萝芷已被证明可以对抗氧化应激、促进持续注意力和改善记忆力187。临床前和临床研究都支持使用碧萝芷进行认知支持188,189。例如,碧萝芷被证明可以减轻帕金森病患者认知障碍的进展190。此外,在阿尔茨海默病的小鼠模型中,补充碧萝芷可以减少β-淀粉样蛋白斑块的数量,并改善记忆的某些方面191。
- 提升NAD+:NAD+是一种通用的辅因子,在氧化还原生物化学反应中发挥关键作用,通过氧化还原反应转化为还原形式NADH。此外,NAD+似乎参与调节酶,这些酶控制一系列细胞功能,包括基因表达、代谢、DNA修复、细胞凋亡和衰老195,196。
更多内容可点击其个性化的综合干预方案如下:
- 认知退化防控(改善脑循环)
- 认知退化防控(神经保护)
- 认知退化防控(维持神经递质)
- 认知退化防控(抗氧化应激)
- 认知退化防控(脑能量激活)
- 轻度认知障碍防控(45-55岁)
- 轻度认知障碍防控(56-65岁)
- 轻度认知障碍防控(66-72岁)
- 轻度认知障碍防控(73岁以上)
以及参阅本网如下专文的相关内容:
医疗干预
治疗目标防止、延缓记忆丧失和其他认知功能,预防阿尔茨海默病(老年痴呆)。
一般治疗措施包括如下:
研究人员在研究几种药物对延缓认知衰退可能产生的影响,包括:
- 胆碱酯酶抑制剂,用于治疗老年痴呆药,以改善记忆。但一般不建议用于治疗MCI。
- 心境稳定剂
- 高血压、高血脂、高血糖
- 抑郁症
- 睡眠呼吸暂停
预防
以下措施有助于降低MCI发生几率:- 管理好慢性病,尤其是高血压、高血脂和糖尿病等。
- 管理好精神症,如抑郁症、焦虑症。
- 保持脑活动能力,如记忆练习、填字游戏、阅读和上课。
- 经常锻炼。
- 参加社会活动。
- 减轻压力。
- 吃健康饮食。
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参考来源:
美国梅奥诊所
www.mayoclinic.org
美国精神病协会
https://www.psychiatry.org
美国国立公众健康网
www.medlineplus.gov
美国国立抗衰老研究所
https://www.nia.nih.gov
加拿大阿尔茨海默病学会
http://www.alzheimer.ca
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