非痴呆性血管性认知功能障碍的中、西医研究现况

非痴呆性血管性认知功能障碍是血管性认知功能障碍的早期阶段,具有可逆性,故对该病的防治倍受关注。本文就目前中、西医对非痴呆性血管性认知功能障碍的认识及其治疗方法作一概述,以期为该病的临床治疗和科研活动提供一些新思路。     

Profile of cholinomimetic drugs in primates: Status of screens for potential Alzheimer therapies

Criticism of the validity of preclinical screens for cognitive enhancers and unsuccessful attempts at cholinotherapy for Alzheimer's disease cast doubt on the likely efficacy of such treatment. However, inadequacies of existing cholinergic drugs and inconclusive clinical trials leave unanswered the question of whether symptomatic relief from dementia can be achieved. Preclinical screens using primates may provide valuable information to support selection of appropriate compounds for clinical development. At present it is not possible to routinely screen cholinergic agents in a manner which provides convincing evidence for beneficial cognitive effects of known relevance for Alzheimer's disease. However, direct comparison of the in vivo effects of a range of cholinomimetic agents in primates has assisted selection of a novel cholinesterase inhibitor, eptastigmine (L-689,487). In rhesus monkeys, the cholinesterase inhibitors physostigmine and eptastigmine, but not tacrine, were able to fully reverse scopolamine-induced performance deficits in a visuospatial task. The duration of action of eptastigmine was considerably longer following oral administration (around 4.5 hr) than for physostigmine (approximately 30 min). In contrast, the directly acting, nonselective muscarinic agonists pilocarpine and RS86 were able to induce only partial reversal of the central effects of scopolamine, apparently due to dose-limiting toxicity. Similarly, the selective M₁/M₃ direct agonists AF1026 and L-689,660 caused only partial or no reversal of the scopolamine-induced impairment. The superior in vivo profile of eptastig- mine should enable more definitive evaulation of cholinotherapy for Alzheimer's disease. © 1992 Wiley-Liss, Inc.     

尼莫地平治疗血管性非痴呆认知障碍的疗效观察

目的：探讨尼莫地平治疗血管性非痴呆认知障碍的改善作用。方法：76例血管性非痴呆认知障碍患者随机分为A组39例和B组37例。两组均给予常规治疗（包括阿司匹林片100 mg·d^-1,阿托伐他汀钙20 mg·d^-1）,A组在此基础上加用尼莫地平片30 mg,po,tid。疗程均为12周。治疗前后均运用蒙特利尔认知评分量表（MOCA）评分和简易精神状态评分量表（MMSE）对临床疗效进行评价。结果：治疗后,A组MMSE评分、MOCA评分均较治疗前明显提高（P〈0.05）,且显著高于B组评分（P〈0.05）。B组治疗前后两项评分差异均无统计学意义（P〉0.05）。A组总有效率明显高于B组（P〈0.05）。两组患者治疗过程中均未出现药品不良反应。结论：尼莫地平对血管性非痴呆认知障碍有防治作用。     

《中国卒中后认知障碍管理专家共识》解读

中国是卒中和痴呆的大国,卒中后认知障碍是卒中常见的并发症,不仅严重影响患者生活质量,而且显著降低卒中患者的生存时间,给家庭及社会带来了沉重的负担。卒中后早期干预可以减少血管性痴呆的发生,血管性因素的可控性为痴呆的治疗提供了新的思路。《中国卒中后认知障碍管理专家共识》将切实指导临床,使得卒中患者的生活质量得以提高。     

石杉碱甲改善认知功能的临床研究进展

认知功能障碍常见于各种痴呆患者,其中阿尔采末病是最常见的。从我国传统中草药蛇足石杉分离提取到的石杉碱甲,是一种高效、可逆的选择性乙酰胆碱酯酶抑制剂,对阿尔采末病患者的认知功能有明显的提升作用。随着临床研究的不断扩大和深入,发现石杉碱甲同样可以很好地治疗血管性痴呆及精神分裂症、帕金森病、糖尿病等引起的认知功能障碍,具有非常广阔的临床应用前景。本文综述了近年来石杉碱甲单独用药以及合并用药缓解认知功能障碍的临床应用研究进展,以期为今后的合理用药提供线索。     

痴呆和认知功能障碍患者用药现状调查分析

目的：调查了解北京大学人民医院诊断为痴呆及认知功能障碍患者的药物治疗现状。方法：提取2018年1月至2019年12月门诊首诊断为痴呆及认知功能障碍的患者处方信息,对患者年龄、性别、用药种类、频率及合理性等进行统计分析。结果：1 063名患者处方信息中首诊断为痴呆者895人,首诊断为认知功能障碍者168人。65岁以下患者人数占比痴呆组显著低于认知功能障碍组,85岁以上患者人数占比痴呆组显著高于认知功能障碍组（P<0.01）。2年间痴呆患者平均每人开具过（7.11±8.37）种药品,显著高于认知功能障碍患者的（3.16±3.69）种（P<0.01）;痴呆患者一线药物胆碱酯酶抑制剂多奈哌齐的使用率显著高于认知功能障碍患者（P<0.01）,改善精神行为症状（BPSD）的药物使用率高于认知功能障碍患者;痴呆患者的多种药物联用方案之间存在药物相互作用等潜在用药风险;老年患者需注意药物联用时跌倒风险的增加。结论：痴呆患者促认知药物及针对BPSD的药物使用率显著高于认知功能障碍患者,应关注潜在联合用药风险。     

血管性认知功能障碍及其早期识别与干预的研究进展

血管性认知功能障碍（vascular cognitive impairment, VCI）是指由脑血管病及其危险因素引起的以不同程度认知功能损害为特点的一组临床综合征。在发展至血管性痴呆之前,早期诊断、早期干预可以预防和延缓VCI的发展,甚至逆转患者的认知功能损害。本文就VCI的概念、发病机制、生物学标志物及其预防和治疗等方面的研究进展作一综述。     

养血清脑颗粒治疗血管性认知功能障碍疗效的Meta分析

目的 评价养血清脑颗粒治疗血管性认知功能障碍的疗效.方法 通过计算机检索工具检索、手工检索,全面搜集养血清脑颗粒治疗血管性认知功能障碍的随机对照实验,按Cochrane协作网发布的RevMan 5.2软件对多个研究结果的总体效应进行Meta分析.结果 共纳入8个试验(579例患者),其中8个试验均对简易智力状态检查表进行评分,显示养血清脑颗粒提高简易智力状态检查表评分优于对照组[WMD=2.47,95%CI(1.57,3.37)];4个试验对患者长谷川痴呆量表进行评分,提示养血清脑颗粒提高长谷川痴呆量表评分优于对照组[WMD=4.80,95%CI(3.94,5.67)];4个试验对患者日常生活能力量表进行评分,显示养血清脑颗粒提高日常生活能力量表评分优于对照组[WMD=-4.43,95%CI(-5.75,-3.12)];4个试验对患者有效率进行评定,提示养血清脑颗粒的疗效优于对照组[OR=2.87,95%CI(1.67,4.94)];结论 养血清脑颗粒治疗血管性认知功能障碍有效.     

血管性认知功能损害的病理机制与预防

血管性认知损害（VCI）是一种异质性疾病,由脑血管病变或脑灌流受损引起,涵盖了从轻微认知损害到血管性痴呆（VaD）。本文综述VCI的病理机制及其预防研究进展。     

补肾活血方联合盐酸多奈哌齐对血管性痴呆患者认知功能与血液流变学的影响

目的 研究补肾活血方联合盐酸多奈哌齐对血管性痴呆患者认知功能与血液流变学的影响。方法 选取92例血管性痴呆患者,按随机数表法分为研究组及对照组,各46例。对照组给予常规治疗并口服盐酸多奈哌齐,研究组在对照组基础上给予补肾活血方,比较治疗前后2组患者日常生活能力量表（activity of daily living,ADL）评分、长谷川痴呆量表（hasegawa dementia scale,HDS）评分、简易精神状态量表（minimum mental state examination,MMSE）评分、血液流变学指标水平（红细胞压积、血浆黏度、全血低切还原黏度与高切还原黏度）、炎症因子水平、中医症状评分及治疗有效率。结果 治疗后,研究组HDS、MMSE与ADL评分均明显优于对照组（P<0.01）;血液流变学指标、炎症因子水平较对照组显著改善（P<0.01）;中医症状改善明显优于对照组（P<0.05）;研究组治疗有效率高达93.48%,对照组为73.91%,差异有统计学意义（P<0.05）。结论 血管性痴呆患者给予补肾活血方联合盐酸多奈哌齐治疗更有利于提高HDS、MMSE与ADL评分,改善中医症状与认知能力,缓解炎症反应,降低血液流变学指标,治疗效果更为显著。     

上海地区老年记忆障碍义诊的参加人群分析

目的：了解老年记忆障碍义诊人群的特点。方法：在公共媒体上发布每周六义诊信息,对来访人群先由心理评估员记录一般人口学特征（性别、年龄、文化程度）,采用简明智能筛查量表（MMSE）评估,再由临床医师进行诊断并提供咨询建议。诊断分为主诉健忘（subjective memory complaints,SMC）、轻度认知功能损害（mild cognitive impairment,MCI）和痴呆（dementia,D）三组。结果：共义诊621人次,剔除重复就诊、代询、非认知损害就诊及资料不全者,最后纳入统计分析的为368例。368例就诊者中,诊断为SMC194例（占52.7%）、MCI82例（占22.3%）、D92例（占25%）,三组间在性别、年龄、文化程度方面有显著性差异。结论：义诊方式有助于早期发现与干预老年期痴呆。     

加味温胆汤联合尼莫地平片治疗非痴呆型血管性认知功能障碍的临床效果观察

目的：观察加味温胆汤联合尼莫地平片治疗非痴呆型血管性认知功能障碍（VCIND）痰瘀阻络型患者的临床效果。方法将89例VCIND痰瘀阻络型患者随机分为中医治疗组29例、西医治疗组30例和中西医治疗组30例。中医治疗组以温胆汤加味,西医治疗组口服尼莫地平片,中西医治疗组以加味温胆汤和西药尼莫地平为主,3组均以10周为1个疗程。治疗前后采用日常生活活动能力（ADL）评定量表、蒙特利尔认知评估量表（MoCA）进行评分。结果3组治疗后ADL及MoCA评分均高于治疗前,差异有统计学意义（P〈0.05）;且中西医治疗组评分高于中医治疗组及西医治疗组（P〈0.05）。治疗期间,3组未出现明显的不良反应。结论加味温胆汤联合尼莫地平片治疗VCIND痰瘀阻络型患者安全有效。     

高敏C-反应蛋白与老年神经系统疾病

高敏C-反应蛋白（hs—CRP）作为一项重要的炎性标志物,参与了动脉粥样硬化、脑血管疾病以及认知功能损害等老年神经系统疾病的发生发展。血清hs—CRP浓度与老年神经系统疾病的发病,病变程度及临床预后密切相关,并且对老年神经系统疾病的预防、治疗、预后判断有重要指导意义。     

Light-to-moderate drinking and dementia risk: The former drinkers problem re-visited

A growing literature ostensibly supports the contention that light-to-moderate drinking offers a protective effect with respect to late-onset dementia. The former drinkers problem, however, may mitigate or even erase any observed protective relationship. Using three recent meta-analyses as windows on the alcohol and dementia literature [Anstey, K.J., Mack, H.A., & Cherbuin, N. (2009). Alcohol consumption as a risk factor for dementia and cognitive decline: Meta-analysis of prospective studies. American Journal of Geriatric Psychiatry, 17, 542–555; Peters, R., Peters, J., Warner, J., Beckett, N., & Bulpitt, C. (2008). Alcohol, dementia and cognitive decline in the elderly: A systematic review. Age Ageing, 37, 505–512; Neafsey, E.J., & Collins, M.A. (2011). Moderate alcohol consumption and cognitive risk. Neuropsychiatric Disease and Treatment, 7, 465–484], we offer a critical review and re-examination of 24 studies employing one or another strategy to control or evaluate the impact of the former drinkers problem on the alcohol and cognitive impairment relationship. Our review is organized around four strategies and problem areas found in these studies, namely: (1) analyses using light drinkers instead of abstainers as reference, (2) time dimension problems attaching to the nondrinker category in analyses, (3) analyses excluding former drinkers or drinkers who changed categories over a study's course, and (4) other approaches and associated problems. Our review suggests that the former drinkers problem has been only incompletely addressed in this still new literature on alcohol's possible protective cognitive effects. As evidenced in the three meta-analyses employed in this review, only a fraction of alcohol and dementia studies addressed the former drinkers problem and, among those, still fewer addressed the problem adequately. Several reasons for this deficiency in the literature are discussed. We conclude that the impact of former drinkers on the alcohol and dementia relationship remains an open question.     

盐酸美金刚治疗PDD对患者认知及生活能力的影响

目的 探讨盐酸美金刚治疗帕金森病性痴呆(PDD)对认知及生活能力的影响.方法 PDD患者104例随机分为观察组和对照组,每组52例,对照组给予盐酸多奈哌齐片治疗,观察组在对照组的基础上给予盐酸美金刚治疗,比较2组蒙特利尔认知评估量表(MoCA)、简易智能状态检查量表(MMSE)和日常生活能力巴塞尔(Barthel)指数评估结果,同时检测患者炎性因子[白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)、干扰素-γ(IFN-γ)]水平.结果 观察组治疗第4、8、16周MoCA评分、MMSE评分明显高于对照组,差异有统计学意义(P<0.05);治疗前,2组Barthel指数比较差异无统计学意义(P>0.05);治疗后,观察组Barthel指数明显高于对照组,差异有统计学意义(P<0.05);观察组治疗后IL-1β、TNF-α较治疗前明显降低,差异有统计学意义(P<0.05),而IL-2和IFN-γ无显著变化(P>0.05);对照组治疗前后各炎性因子无显著变化(P>0.05);2组不良反应发生率比较差异无统计学意义(P>0.05).结论 盐酸美金刚能有效改善PDD患者的认知及生活能力,同时抑制局部和全身炎性反应,且安全可靠.     

丁苯酞软胶囊联合盐酸多奈哌齐治疗血管性痴呆的临床研究

目的探究丁苯酞软胶囊联合盐酸多奈哌齐片治疗血管性痴呆的临床疗效。方法选取2017年3月-2018年3月中国人民武装警察部队特色医学中心收治的96例血管性痴呆患者为研究对象,根据随机数字表法将所有患者分为对照组和治疗组,每组各48例。对照组口服盐酸多奈哌齐片,初始剂量1片/次,1次/d,维持4周,随后根据治疗效果增至2片/次,1次/d,再持续治疗4周。治疗组在对照组治疗的基础上口服丁苯酞软胶囊,2粒/次,3次/d。两组患者均持续治疗8周。观察两组的临床疗效,比较两组的蒙特利尔认知评估量表(Mo CA)评分、血清因子水平、血液流变学指标、阿尔茨海默病生活质量测评量表(QOL-AD)评分。结果治疗后,对照组和治疗组的总有效率分别为77.08%、93.75%,两组比较差异有统计学意义(P<0.05)。治疗后,两组患者视空间执行力评分、注意力评分、延迟回忆评分、定向力评分和Mo CA总分均较治疗前升高(P<0.05);且治疗组Mo CA评分指标均明显高于对照组(P<0.05)。治疗后,两组患者血清胶质细胞源神经营养因子(GDNF)水平升高,白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平降低,同组治疗前后比较差异有统计学意义(P<0.05);且治疗组患者GDNF较对照组高,而IL-6、TNF-α均明显低于对照组,两组比较差异有统计学意义(P<0.05)。治疗后,两组患者全血低切黏度、全血中切黏度、全血高切黏度均较治疗前降低,同组治疗前后比较差异有统计学意义(P<0.05);且治疗组患者血液流变学指标均明显低于对照组,两组比较差异有统计学意义(P<0.05)。治疗后,治疗组患者QOL-AD评分明显升高,同组治疗前后比较差异有统计学意义(P<0.05);并且治疗组患者QOL-AD评分明显高于对照组,两组比较差异有统计学意义(P<0.05)。结论丁苯酞软胶囊联合盐酸多奈哌齐片治疗血管性痴呆具有较好的临床效果,可改善患者认知功能,调节血清因子和血液流变学指标,改善生活质量,具有一定的临床推广应用价值。     

Ginkgo biloba: specificity of neuropsychological improvement—a selective review in search of differential effects

Extracts of Ginkgo biloba are widely used for the treatment of cognitive impairment. Whereas reviews have focused on the question whether ginkgo is effective to enhance cognition in general, little is known about specificity of improvement. This might be crucial for future trials, thus enabling hypotheses about sensitive outcome measures. Therefore, this article summarizes such information, i.e. neuropsychological effects of chronic administration of ginkgo in healthy and cognitively impaired subjects of any age. Objective psychometric test results were considered if they reflected distinct cognitive functions from randomized controlled group‐studies (RCT). We reviewed 29 RCTs yielding 209 placebo‐drug comparisons of psychometric scores in four different cognitive domains comprising 14 sub‐functions. Whereas little specific information can be obtained from trials for treatment of dementia, a pattern of pharmacological actions on cognitive processes emerges here from studies for mild cognitive impairment (MCI), depression, multiple sclerosis and healthy young and elderly subjects. There is consistent evidence that chronic administration improves selective attention, some executive processes and long‐term memory for verbal and non‐verbal material. Further trials should be more comprehensive as there are few data available on some cognitive functions and psychometric flaws in the selection of tests and the interpretation of their results favouring predominantly β‐errors. Thus, though this pattern is encouraging it also asks for a cautious interpretation to date. Copyright © 2009 John Wiley & Sons, Ltd.     

A double‐blind,placebo‐controlled single dose trial of intravenous flumazenil in Alzheimer's disease

Benzodiazepine agonists have been shown to reduce cognitive functioning by producing attentional deficits similar to those produced by muscarinic antagonists. It has therefore been postulated that benzodiazepine antagonists may improve cognitive function in patients with Alzheimer's disease by indirectly increasing cholinergic function. Eleven patients with mild to moderate Alzheimer's disease took part in a double‐blind placebo‐controlled crossover study of the effects of a single 1 mg injection of the benzodiazepine antagonist flumazenil on cognitive function. Validated computer tests were used to assess change in cognitive function over time after each injection. No adverse effects of the drug were experienced. Speed on both a simple reaction time task and a picture recognition task was significantly slowed by flumazenil compared to placebo at 15 min (p=0.027 and p=0.01). Accuracy of recalling pictures was significantly reduced compared to baseline (p=0.0002), but this was not statistically significant when compared to placebo. Possible reasons for these findings are discussed and it is concluded that a single injection of 1 mg flumazenil produces cognitive slowing in patients with Alzheimer's disease. It is suggested that further research is needed into central benzodiazepine receptor density and function, as well as dose–response studies using flumazenil. Copyright © 1999 John Wiley & Sons, Ltd.