摘要
一、黄连温胆汤加味治疗老年轻度认知障碍痰浊阻窍证的临床研究
对老年轻度认知障碍积极进行干预是延缓老年认知功能进一步衰退的有效措施,为老年期痴呆寻找最佳干预时间,减轻家庭负担和社会负担有重大的理论和现实意义。本部分研究是对老年轻度认知功能障碍患者的中医临床研究。
[目的]探讨黄连温胆汤加味治疗老年轻度认知障碍的临床疗效。
[方法]采用区组随机、双盲、对照的设计原则,将入选病例64例随机分为中药治疗组(n=32例)和阳性对照组(n=32例)。治疗组给予内服黄连温胆汤加味汤剂,每次200ml,每天2次;对照组给予口服茴拉西坦胶囊,每次2粒,每天3次。两组均观察用药3个月,并进行随访1年。主要观察患者的中医证候、认知能力(MMSE)、记忆水平(DSR)、日常生活活动能力(ADL)、实验指标(hch、SOD、MDA)及相关安全性指标变化。
[结果]
1证候治疗前后比较
黄连温胆汤加味治疗组和茴拉西坦胶囊对照组治疗前后中医症状积分比较,组间比较采用成组t检验,结果示治疗后,治疗组智能减退(健忘)、头沉或头昏不清、泛恶欲呕、纳呆腹胀、肢体困重积分及总积分较对照组明显提高,统计分析有差异(P<0.01或P<0.05),痰多吐涎症较对照组,统计分析无差异(P>0.05)。
组内比较采用配对T检验,结果示治疗组治疗后智能减退(健忘)、头沉或头昏不清、泛恶欲呕、纳呆腹胀、肢体困重症状积分及总积分较治疗前明显改善,统计有显著性差异(P<0.01或P<0.05),痰多吐涎症积分较治疗前,统计分析无差异(P>0.05);对照组治疗后智能减退(健忘)、头沉或头昏不清、肢体困重症状积分较治疗前明显改善,统计分析有差异(P<0.05),泛恶欲呕、纳呆腹胀、痰多吐涎症状积分及总积分较治疗前,统计分析无差异(P>0.05)。提示黄连温胆汤加味治疗老年轻度认知障碍患者后,两组患者症状积分均较治疗前有改善;与对照组比较疗效优于茴拉西坦胶囊。
2认知能力治疗前后比较
两组治疗前后认知能力评分比较,组间比较采用成组t检验,结果示治疗后治疗组定向、记忆、计算及总积分均较对照组明显改善,统计有显著性差异(P<0.05或P<0.01),两组语言积分比较无显著性差异(P>0.05);组内比较采用配对T检验,结果示治疗组除语言积分外,其余各项及总积分均较疗前明显改善(P<0.05或P<0.01),对照组除定向积分外,其余各项和总积分较疗前改善明显(P<0.05)。
3记忆水平治疗前后比较
治疗组和对照组治疗前后DSR比较,组间比较采用成组t检验,结果示治疗后治疗组较对照组DSR积分提高,统计分析无差异(P>0.05);组内比较采用配对T检验,结果示治疗组治疗后DSR较治疗前明显改善,统计有显著性差异(P<0.01),对照组治疗后DSR积分较治疗前明显改善,统计分析有差异(P<0.05)。提示黄连温胆汤加味治疗老年轻度认知障碍患者后,两组患者DSR积分均较治疗前明显提高;与茴拉西坦胶囊对照组比较疗效无差异。
4日常生活能力治疗前后比较
治疗组和对照组治疗前后ADL比较,组间比较采用成组t检验,结果示治疗后治疗组较对照组ADL积分明显提高,统计分析无差异(P>0.05);组内比较采用配对T检验,结果示治疗组治疗后ADL积分较治疗前明显改善,统计有显著性差异(P<0.01),对照组治疗后ADL积分较治疗前明显改善,统计分析有差异(P<0.01)。提示黄连温胆汤加味治疗老年轻度认知障碍患者后,两组患者ADL积分均较治疗前明显提高;与茴拉西坦胶囊对照组比较疗效无差异。
5 Ach、SOD、MDA治疗前后比较
治疗组和对照组治疗前后血清Ach比较,组间比较采用成组t检验,结果示治疗后治疗组较对照组血清Ach含量明显提高,统计分析有差异(P<0.05);组内比较采用配对T检验,结果示治疗组治疗后血清Ach含量较治疗前明显改善,统计有显著性差异(P<0.01),对照组治疗后血清Ach含量较疗前明显改善,统计有显著性差异(P<0.01)。提示黄连温胆汤加味治疗老年轻度认知障碍患者后,两组患者血清Ach含量均较治疗前明显提高;黄连温胆汤加味治疗组疗效明显优于茴拉西坦胶囊对照组。
治疗组和对照组治疗前后SOD、MDA比较,组间比较采用成组t检验,结果示治疗后治疗组较对照组SOD、MDA提高,统计分析无差异(P>0.05);组内比较采用配对T检验,结果示治疗组治疗后SOD、MDA积分较治疗前明显改善,统计有显著性差异(P<0.01),对照组治疗后SOD、MDA积分较治疗前明显改善,统计分析有差异(P<0.01)。提示黄连温胆汤加味治疗老年轻度认知障碍患者后,两组患者各自较治疗前SOD、MDA积分改善;与茴拉西坦胶囊对照组比较疗效无统计学差异。
安全检测显示本研究所用方药无不良反应,用药安全。
[结论]黄连温胆汤加味在改善老年轻度认知障碍痰浊阻窍证患者的症状、认知能力、提高Ach含量方面疗效优于茴拉西坦胶囊;在改善日常生活活动能力、提高血清SOD活性、降低血清过氧化脂质的代谢产物MDA方面与茴拉西坦胶囊疗效近似。
二、中医药治疗老年轻度认知障碍的临床疗效评价
目前关于轻度认知功能障碍干预措施的报道较少,而关于轻度认知功能障碍的干预策略多沿袭了老年痴呆的治疗方案。目前,对老年轻度认知障碍的干预治疗尚缺乏特效,而且有的药物属于化学制剂,不可避免地对老龄患者产生毒副作用,且高昂的价格也给老年人及其家庭带来了沉重的经济负担。
对轻度认知功能障碍的中医研究亦很少,例如还脑益聪胶囊合灯盏花素联用对降低血液黏稠度、改善大脑动脉血流量有显著作用等。但是对于中医药治疗老年轻度认知障碍的效果尚缺乏系统评价,因此本研究拟系统评价中医药治疗老年轻度认知障碍的有效性和安全性,为我国老年轻度认知障碍的中医药干预提供决策参考。
[目的]对目前中医药治疗轻度认知障碍的临床疗效评价。
[方法]采用手工和计算机检索文献,检索数据库如Cochrane图书馆、PubMed、EMBASE、中国生物医学文献数据库(CBM)、中国知网(CNKI)、维普数据库(VIP)等数据库。其他检索来源:全球或地区相关MCI的中医药会议、政府或非政府组织相关资料等。由两名研究者独立筛选文献和进行文献筛选、质量评价、数据提取、交叉核对,不同意见与第三方讨论解决。采用Cochrne协作网提供的RevMan 5.0进行荟萃(Meta)分析。
[结果]文献筛选结果共获得相关文献118篇,经过剔重、阅读题目、摘要和全文后,排除疗程不符合标准,疗效评价指标不明确等的106篇文献,最终纳入12篇合格文献。本研究共纳入12篇中文随机对照研究,均为中药复方制剂,有颗粒、胶囊、丸剂、口服液等剂型。本研究纳入的12篇文献,皆提及随机对照试验,仅2项研究报告随机序列产生的方法;3项研究报告分配方案隐藏;7项研究采用盲法,大部分纳入研究质量较低。
本系统评价结果表明目前常见研究中药以复方为主,如上述金思维丸、还脑益聪胶囊、加味五子衍宗颗粒、参银口服液、参乌胶囊等。主要治疗肾虚、气虚、血瘀等证为主。治法主要是补肾、健脾、益气、活血化瘀等为主。疗效评价以神经心理测量量表、社会和生活功能量表为主,如MMSE、MQ、FAQ等。
由治疗前后MMSE和MQ积分变化,可知中药治疗组改善认知水平明显优于西药对照组。
由治疗前后FAQ积分变化观察社会活动功能有改善,中药治疗组与西药对照组疗效无差异。
[讨论]中药治疗组治疗老年轻度认知障碍在认知改善方面优于西药对照组,但在社会生活功能改善方面与西药对照组疗效近似。目前现有研究证据证实中药治疗老年轻度认知障碍有效和安全,应再进一步研究和临床推广应用。
1.Clinical research
Introduction
It is effective measure to intervene actively senile Mild Cognitive Impairment for deferiing decline of cognitive function.In other words,dementia was delayed.It is great academic and realistic significance to relieve family and social burden.
Objective
To observe the clinical efficacy of Coptis Decoction for Clearing Away Gallbladder-heat on thetreatment in the elderly with mild cognitive impairment (MCI).
Methods
The research design principle was block random,double-blind and controlled.64 patients with MCI were selected and were randomly assigned into a treatment group (30 cases),given 200ml of compound Chinese herb with 2 grain placebo,and a positive control group(30 cases),given 2 grain of Aniraectam capcle with 200ml placebo,The capsule was taken 3 times and the compound Chinese herb was taken 2 times a day.All subjects took this medication for 3 months.At the starting point and a point after 3months,all subjects were assessed by MMSE、syndrome、DSR、ADL、Ach、and SOD,et cl.
Results
MMSE score was increased from 24.81±1.69 at starting point to 27.22±1.87 at the point of after 3 months of the treatment in the treatment group,which was significantly higher than that in the control group(P<0.01).Ach score was significantly increased from 11.40±6.12 at Starting point to 21.43±9.72 at the point of after 3 months of the treatment in the treatment group,which was significantly higher than that in the control group(P<0.05).The total score of syndrome was increased in the treatment group,significantly higher than that in control group(P<0.05).
The score of MMSE、syndrome、Ach In the treatment group was higher than that in the control group on syndrome、MMSE、Ach(P<0.05).
ADL、DSR、SOD、MDA score was increased after 3 months of the treatment In the treatment group(P<0.05),but the score In the treatment group was not higher than that in the control group on syndrome、MMSE、Ach.
Conclusion
The effect of Coptis Decoction for Clearing Away Gallbladder-heat is superior to Aniraectam capcle's on syndrome、MMSE、Ach.Both Coptis Decoction for Clearing Away Gallbladder-heat and Aniraectam capcle have protective effect on memory decline、ADL、SOD and MDA in elderly with MCI.
2.Evaluation of therapeutic efficiency
The 12 documents all mentioned random in this research,but only two studies described the methods of generating random sequence,and so on.The quality of most of these documents is lower.The results of SR indicate that traditional Chinese medicine used in existing research is mainly in compound,and the primary therapy is tonify the kidney.In addition,tonifying qi and activating blood are also applied.Evaluation of therapeutic efficiency give priority to neuro-psychological measurement scale and Social and functional life scale,such as MMSE、FAQ.It is showed that therapeutic efficiency of TCM treatment group is quite effective for improving cognition in senile Mild cognitive impairment than control group,but there was no difference in the social life function.
引文
[1]李娌,王学美,富宏,等.轻度认知障碍患者记忆损伤与中医证型的关系[J].中国组织工程研究与临床康复,2007,77(39):7826-7829.
[2]宋萍,王学美,富宏,等.轻度认知障碍中医辨证分型与自由基代谢和胆碱酯酶的相关性研究[J].中医杂志,2005,46(4):291-293.
[3]田金洲,杨承芝,盛彤,等.可疑痴呆人群中阿尔茨海默氏病临床前的认识损害特征及其与中医证候的关系[J].湖北中医学院学报,1999,1(4):49-55.
[4]杨志敏,谢东平,陈淑慧,等.老年人轻度认知功能障碍的中医证候分布情况初步研究[J].世界中西医结合杂志,2007,2(4):912-914
[5]杨承芝,钟剑,朱爱华,等.老年人轻度认知损害的中医证候研究[J].北京中医药大学学报(中医临床版),2003,10(2):12-16.
[6]何迎春,张如富.轻度认知障碍的中医辨证分型[J].辽宁中医杂志,2006,33(1):1464.
[7]张雅萍,王兴臣,付强,等.轻度认知障碍中医证候流行病学研究[J].北京中医药大学学报,2007,30(10):709-712.
[8]宋萍,王学美,富宏,等.轻度认知障碍老年人中医证型与记忆损伤及cT变化的相关性[J].中国临床康复,2006,10(3):9-11.
[9]杨养贤,李锐,陈松盛,等.补肾化瘀法改善缺血性认知障碍作用机理研究[J].中国中医基础医学杂志,2001,7(1):15-17.
[10]王学美,富宏,宋萍,等.从神经心理学和影像学探讨加味五子衍宗颗粒对轻度认知障碍患者的影响[J].中国老年学杂志,2001,24(4):299-301.
[11]王学美,富宏,刘庚信,等.加味五子衍宗颗粒治疗轻度认知障碍的临床研究[J].中国中西医结合杂志,2004,24(5):392-395.
[12]富宏,王学美,刘庚信,等.加昧五子衍宗颗粒对轻度认知障碍患者记忆功能及海马体积的磁共振研究[J].中国中西医结合杂志,2006,26(12):1066-1069.
[13]王学美,富宏,刘庚信,等.加味五子衍宗颗粒对轻度认知障碍患者的影响[J].中国中西医结合急救杂志,2008,15(3):159-i62.
[14]钟剑,朱爱华,杨承芝,等.参乌胶囊治疗老年轻度认知损害临床对照研究[J].中国中药杂志,2007,32(17):1800-1803.
[15]何迎春,何烨,李谨,等.健脾填精方治疗轻度认知障碍21例疗效观察[J].新中医,2005,37(12):42-43.
[16]王健,张守琳,任玺洁.脑力宝改善老年人记忆功能障碍属肝肾阴虚证随机对照研[J].中国实验方剂学杂志,2002,8(2):48-50.
[17]田金洲,朱爱华,钟剑,等.金思维治疗社区轻度认知损害老年患者记忆减退症状的1年随访[J].中国中药杂志,2003,28(10):987-991.
[18]李浩,刘芳,徐立然,等.还脑益聪胶囊对老年轻度认知障碍的影响[J].中国中西医结合杂志,2004,24(8):689-693.
[19]周如倩,林水淼,袁泉.参银口服液治疗轻度认知功能损害的临床研究[J].中国中西医结合杂志,2007,27(9):793-795.
[20]戈继业,张振岭.川芎药理作用研究及临床应用新进展[J].中国中西医结合杂志,1994(10):638-644.
[21]雷平,李应续,雷亚宁,等.川芎嗪对大鼠脑缺血再灌注损伤的保护作用[J].咸宁医学院学报,2000,14(2):56-61
[22]张旭静,曹奕丰,冯春红,等.川芎、当归对大鼠血栓形成的影响[J].中国临床药学杂志,2002,11(1):45-47
[23]陈维洲,张培智.银杏叶提取物的药理和临床研究进展[J].新药与临床杂志,1999,18(5):315-317.
[24]马东晓.银杏叶提取物的抗氧化功能[J].中国临床康复,2004,8(27):5814-5820.
[25]吴兴利,王士雯,徐雅琴,等.银杏叶提取物对兔血管平滑肌分泌细胞因子的影响[J].中国新药与临床杂志,2003,22(5):292-295.
[26]沈立,郭芳,王永利,等.银杏叶提取物对缺血再灌注大鼠脑内SOD,GSH2Px 和MDA的影响[J].中国新药与临床杂志,2004,23(10):691-694.
[27]唐洪梅,李锐,周莉玲,等.石菖蒲对中枢神经系统作用研究进展[J].广州中医药大学学报,2000,(2):21-24.
[28]徐江平,杨雪梅,等.中草药活性成分防治阿尔茨海默病的研究进展[J]. 第一军医大学学报,200l,(1):23-25.
[29]孙远征,祝鹏宇,张淼,等.原络通经针法治疗轻度认知障碍临床观察[J].中国针灸,2007,27(11):810-812.
[30]薛腊梅,闻红斌,章军建.电刺激小脑顶核对轻度认知障碍患者脑血流的影响[J].中国临床康复,2005,8(25):5248-5249.
[31]周洪语,徐继文,邱永明,等.电刺激小脑顶核预处理对缺血脑损害的预防性脑保护作用[J].中国临床康复,2003,7(19):2658-2659.
[1]Petersen RC,Ekx～y R,Kurz A,et al.Current concepts in mild cognitive impairment.Arch Neurol 2001;58:1985-1992.
[2]Hanninen T,Hallikainen M,Tuomainen S.Prevalence of mildcognitive impairment:a population-based study in elderly subjects[J].Acta Neurol Scand,2002,106(3):148-154.
[3]Lopex OL,Jagust WJ,DeKosky ST,et al.Prevalence and classification of mild cognitive impairment in the Cardiovascular HealthStudyCognition Study:part1[J].Arch Neurol,2003,60(10):1385-1389.
[4]Luck T,Riedel-Heller SG,Kaduszkiewicz H,et al.Mild colgnitive impairment in general practice:age-specific prevalence and correlate results from the German study on ageing,cognition and dementiain primary care patients(AgeCoDe)[J].Dement Geriatr Cogn Disord,2007,24(4):307-316.
[5]高橘若生,刘芳,陈谅.轻度认知功能障碍[J].日本医学介绍,2005,26(3):117-119.
[6]邱昌建,唐牟尼,张伟,等.成都地区55岁及以上人群轻微认知障碍损害患病率调查[J].中华流行病学杂志,2003,24(12):1104-1107.
[7]汤哲,张欣卿,吴晓光,等.北京城乡老年人轻度认知障碍患病率调查[J].群体心理卫生,2007,21(2):116-118.
[8]黄若燕,唐牟尼,马崔等.广州市60岁及以上老人轻度认知障碍的患病率调查[J].中国神经精神疾病杂志,2008.34(9):533-537.
[9]关绍晨,汤哲,吴晓光.北京老年人群轻度认知障碍患病情况及危险因素的抽样调查[J].中国脑血管病杂志,2008,5(9):395-398.
[10]Lopez OL,Jagust WJ,Dulberg C,et al.Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognitive Study:part 2[J].Arch Neurol.2003,60(10):1394-1399.
[11]黄若燕,唐牟尼,马崔等.广州市60岁及以上老人轻度认知障碍的患病率调查[J].中国神经精神疾病杂志2008,34(9):533-537.
[12]刘彬,韶红,彭永革等.对深圳罗湖区老年人轻度认知障碍的调查与分析[J].广州中医药大学学报,2005,220:366-376.
[13]汤荟冬,姚玉蕙,徐瑞芳等.上海市郊区老年人认知障碍的相关因素分析[J].中国现代神经疾病杂志,2008,8(4):318-322.
[14]关绍晨,汤哲,吴晓光.北京老年人群轻度认知障碍患病情况及危险因素的抽样调查[J]中国脑血管病杂志,2008,5(9):395-398.
[15]谭纪萍,王鲁宁,王炜.老年人轻度认知功能损伤危险因素的病例对照研究[J].中华流行病学杂志,2006,27:55-57
[16]Skoog I,Lithell H,Hansson L,et al.Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes:Study Oil Cognition and Prognosis in the Elderly(SCOPE)[J].Am J Hypertens,2005,18:1052-1059.
[17]Elias MF,Wolf PA,DAgostino RB,et al.Untreated blood pressure is inversely related to cognitive functioning:the Framingham Study[J].Am J Epidemiol,1993,138:353-364.
[18]Qiu c,Winblad B,Fmfidioni L.The age-dependent relation of blood pressure to cognitive function and dementia[J].Lancet Neurol,2005,4:487-499.
[19]关绍晨,汤哲,吴晓光.北京老年人群轻度认知障碍患病情况及危险因素的抽样调查[J].中国脑血管病杂志,2008,5(9):395-398.
[20]陈伟平,徐书雯,黄越冬.轻度认知障碍和阿尔茨海默病患者血脂及甲状腺激素水平的关系[J].中国老年学杂志,2008.28:2328-2330.
[21]Kivipelto M,Helkala EL,Hanninen T,et al.Midlif vascular risk factorsand late-life mild cangnitive impairment:a population-based study[J].Neurology,2001;56(12):1683-989.
[22]Borroni B,Pettenati T,Serum cholesteml levels modulate long.term efllcacyof Tcinesterase inhibitom in Alzheimer disease[J].Neurosci Lea,2003;343(2):213.
[23]Launer U,White LR,Petmviteh H,et aL.Cholesterol and neuropathologlcInarher8 of AD:a population-based autopsy study[J].Neurogy,2001;57(8):1447.
[24]Kojm E,Gimpl G,Lammlch S,et al.Low cholesterol stimulates thenonamy¨loidogenic pathway by its effect on the alpha-secrettme ADAM[J].Proe Nat[Acad Sci USA,2001;98(10):5815-20.
[25]Kuo YM,Emmerling MR,Bisgaier CL,et al.Elevated low lensity lipoprotein in Alzheimer's disease correlates with brain A{31-42 levels[J].Biochem Biophys Res Commun,2001;252(3):711.
[26]Andreasen N,Vanmeehelen E,Vandemtiehele H,et aL.Cerebrosp inal flu-id levels of total-tau,phospho·tau and A842 predicts development of Alzheimer'8disease in patients with mild cognitive impairment[J].AetaNeural Seand,2003,107(Supp 1179):472-511.
[27]Riemenschneider M,Lautenschlager N,Wagenpfeil S,et aL.Cerebrosp inalfluid tau and beta amyloid 42 proteins identify Alzheimer disease in subjectswith IIlild cognitive impairmen[J].Arch Neural,2002,59:17292-341.
[28]Jick H,Zombcrg GL,Jiek SS,et al.Statins and the risk of dementia[J].Lancet,2000;356(9242):1627-31.
[29]YAFFE K,BARRETt-CONNOR E,LIN F,et al.Serum lipopro-tein levels,statin USe and cognitive function in older women[J].Arch Neurol,2002,59(3):378-384.
[30]杨畅,王希福,张惠敏.老年轻度认知障碍者的血脂改变及认知功能改变特点[J].中国医科大学学,2006,35(3):320-323.
[31]ERICVAN EXEL E,DE CRANE AJ,GUSSEKLOO J,et al.Association between hish-density lipopmtein and cognitive impairment inthe oldest old[J].Ann Neurol,2002,51(6):716-721.
[32]刘立平,耿晓英.老年轻度认知障碍42例血脂检测分析[J].陕西医学杂志,2008,37(9):1224-1226.
[33]BRAUNWALD E,PETER ZL,BONOW R Heart Disease[M].7th ED Philadelphia;W.B.Saunders Compang,2004:216.
[34]宋守君,张杰涛,孙国建等.甲状腺激素水平与老年轻度认知障碍之间的相关性[J].滨州医学院学报,2002,25(6):417-149.
[35]Kalmijn S,Mehta KM,Pols HA,etal.Subclinical hyperthyroidism and therisk of dementia[J].Clin Endocrinol,2000,53(6):733-737.
[36]Ichibangase A,Nishikawa M,1 wasaka T,etal.Relation between thyroidand cardiac function and the geriatric rating scale[J].Aeta NeurolSeand,2002,81:491-8.
[37]陈伟平,徐书雯,黄越冬.轻度认知障碍和阿尔茨海默病患者血脂及甲状腺激素水平的关系[J].中国老年学杂志,2008.28:2328-2330.
[38]Smith JW,Evans AT,Costall B,et al.Thyroid hormones,brain functionand cognition:a brief review[J].Neurosci Biobchav Rev,2002,26:45-60.
[39]Petersen RC,Doody R,Kurz A,et al.Current concepts in mild cognjtive impairment[J].ArcKves of euroIOgy,2001,8(12):1985-1992.
[40]Petersen RC,Stevens JC,Ganguli M,et al.Practice parameter:early detection of dementia:mild cognitive impairment(an evidence-based review)[J].Neurology,2001,56:1133-1142.
[41]Peterson R C,Smith G E,Waring S C,et al.Mlid ccgnitiveimpairment:Clinical characterization and outcome[J].Arch Neuol,1999,56:303-308.
[42]Petersen RC,Doody R,Kurz A,et al.Current concepts in mild cognitive impairment[J].Arch Neural,2001,58:1985-1992.
[43]伍少玲,燕铁斌,黄利荣.简易智力测试量表的效度及信度研究[J].中华物理医学与康复杂志,2003,25:140-142。
[44]段晓宇,江新梅.HDS、MMSE,BBS在痴呆筛查中的应用[J].中风与神经疾病杂志,2002,19(3):167-168.
[45]张善纲,范建中,徐军.脑损伤认知障碍康复评定的进展[J].国外医学·物理医学与康复学分册,2004,24(4):183-185.
[46]Katz N,Elazar B,hzkovich M.Construct Validity of a Geriat-ric Version of the Loewenstein Occupational Therapy Cognitive Assessment(LOTCA)Battery[J].Physical & Occupational Therapy in Geriatrics.1995,13(3):31-46.
[47]燕铁斌,伍少玲,郭友华,等.Loewenstein认知评定量表与简易精神状态检查评定脑损伤患者认知功能的比较[J].中华物理医学与康复杂志,2004,26(7):400-401.
[48]燕铁斌,伍少玲,郭友华,等.Loewenstein认知评定量表与简易精神状态检查评定脑损伤患者认知功能的比较[J].中华物理医学与康复杂志,2004,26(7): 400-403.
[49]张善纲,范建中,陈平雁,等.洛文斯顿作业疗法认知评定中文量表信度和内在效度的初步研究[J].中华物理医学与康复杂志,2004,26(9):530-534.
[50]唐桂华,陈卓铭,李冰肖.汉语认知功能测评量表的比较[J].中国临床康复,2004,8(19):3882-3884.
[51]Fladbuy T.Schuster M,Gronlio et al.Organic brain diseasein psychogeriat ric patients 1 impact if symptoms and screeningmethods on the diagnostic process[J].JGeriatr PsychiatryNeurol,1999,12:16-20.
[52]DoningerNA,Bode RK.Heinemann AW etal.Rating scale a-nalysis of the Neurobehavioral Cognitive Status Examination[J].J Head Trauma Rehabil,2000,15(1):683-695.
[53]朱燕,王毅,王文敏.神经行为认知状态检查介绍(NCSE)[J].中国临床心理学杂志,2003,11(2):151-152.
[54]Oehlert ME,Hass SD,Freeman MR,et al.The NeurobehavioralCognitive Status Examination:accuracy of the "screen-metric" approach in clinical sample[J].clin Psychol,1997,53(7):733-737.
[55]Dai XY,Ryan JJ,Paolo AM,et al.Factor analysis of the ina-inland Chinese version of the Weehsler Adult IntelligenceScale(WAI RC)in a brain-damaged sample[J].Int J Neurosci,1990,55:107-111.
[56]项薇,黄流清.老年轻度认知障碍记忆损害特点的研究[J].中风与神经疾病杂志,2006,23(2):213-215.
[57]黎彬如,毕桂南,邱燕东.轻度认知障碍患者认知功能的临床研究[J].广西医学,2007,29(5):627-628.
[58]沈树红,郭起浩,王少石.视觉和听觉逻辑记忆识别轻度认知障碍的效力比较[J].中国临床心理学杂志,2008,16(2):148-150.
[59]Petersen RC,Smith Waring SC,etal.Mild cognitive impairment clinical characterization and outcome.Arch Neurol,1999,56:303.
[60]Ronald C,Peterson RC.Mild cognitive impairment:Current Research and Clinical Impalication[J].Semin Neurol 2007,27(1):22-31.
[61]Johnson KA,Jones K,Holman BL.Preclinieal Prediction ofAlzheimer'S disease using SPE CT[J].Neurology,1998,50(6):1563-1571.
[62]McKelvey R,Bergman H,Stern J.Lack of prognosticsignificance of SPECT abnormalities in non-demented elderlysubjects with mild memory lossE[J].Can J Neurol Sci,1999,26(1):23-28.
[63]Krasuski JS,Alexander GE,Horwitz B,et al.Volumes ofmedial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment(and in healthy controls)[J].Biol Psychiatry,1998,43(1):60-68.
[64]Delacourte A.Tauopathies:recent insights into old diseases[J].Folia Neuropathol,2005,43:244-257.
[65]贾建平.重视轻度认知障碍与老年性痴呆关系的研究[J].中华神经科杂志2007,7(6):324-326.
[66]王炜,王鲁宁.老年人轻度认知损害的研究进展[J].中华老年心脑血管病杂志,2001,3(3):208-211.
[67]Gomez2Isla T,Prece J,Mckeel DJ,et al.Profound loss of layer entorhinal cortex neurons occurs in very mild Alzheimer disease[J].J Neurosci,1996,16:4491-5000.
[68]Morrison J,Hof P.Life and death of neurons in the ageing brain[J].Science,1997,278:412-419.
[69]Devanand DP,Pradhaban G,Liu X,et al.Hippocampal and entorhinalatrophy in mild cognitive impairment:prediction of Alzheimer disease[J].Neurology,2007,68(11):828-836.
[70]Dubois B,Albert ML.Amnestic MCI or prodromal Alzheimer's disease?[J].Lancet Neurol,2004,3(4):246-248.
[71]MeGeer PL,Schulzer M,McGeer GE.Arthritis and anti-inflammatory agents as possible protective factors forAlzheimefs disease:a review of 17epidemiologic studies[J].Neurology,1996,47(2):425-432.
[72]Andreasen N,Vanmechelen E,Vanderstichele H,et al.Cerebrospinal fluid levels of total-tau,phospho-tau and Abeta 42 predicts development of Alzheimer's disease in patients with mild cognitive impairment[J].Acta Neurol Scand Suppl,2003,179:47-51.
[73]Hampel H,Teipel,Fuchsberger,et al.Value of CSF β-amyloid1-42 and tau as predictors of Alzheimer's disease in patients withmild cognitive impairment[J].Molecular Psychiatry,2004,9:705-710.
[74]Petersen RC,Smith GE,Ivnik RJ,et al 1 Applipoprotein E status as apredictor of the development of Alzheimer's disease in memory impairedindividuals[J].JAMA,1995,273:1274-1278.
[75]Tierney M,Szalai J,Snow W,et all Prediction of propable Alzheimer disease in memory2impaired patients 1 A prospective longitudinal study[J].Neurology,1996,46:6612-6651.
[76]Ganguli M,Dodge HH,Shen C,et al.Mild cognitive impairment,amnestic type:an epidemiologic study[J].Neurology,2004,63:115-121
[77]Luis CA,LoewensteinDA,AcevedoA,et al.Mildcopairment:directions for future research[J].Neurology,2003,61(4):438-444
[78]李玮,王新高,矫黎东等.轻度认知障碍脑脊液细胞因子与Tau蛋白和p淀粉样蛋白的关系[J].临床荟萃,2006,21(19):1394-1396.
[79]Tarkowski E,Andreasen N,Tarkowski A,et al.Intrathecalinflammation precedes development of Alzheimer'sdisease[J].J Neurol Neurosurg Psychiatry,2003,74(9):1200-1205
[80]Seshadri S,BeiserA,SelhubJ,et al.Plasmahomocysteineasariskfactorfordementia and Alzheimer's disease[J].NEnglJMed,2002,346(7):476
[81]Religa D,Styczynska M,Peplonska B,et al.Homocysteine,apolipoprotein e E and methylenetetrahydrofolatereductaseinAlzheimer's disease and mild cognitive impairment[J].Dement GeriatrCognDisord,2003,16(2):64
[82]Malouf M,Grimley EJ,Areosa SA.Folicacidwithorwith outvitam in B12 for cognitionand dementia[J].Cochrane Database SystRev,2003,(4):CD004514
[83]张铭湘,夏家辉.神经退化性疾病生物能量代谢和氧化应激研究进展[J].生命科学研究,2000,4(4)295-301.
[84]Pratico D,Clark CM,LiunF,et al.Increase of brain oxidative stress in mild cognitive impairment:a possible predictor of Alzheimer disease[J].Arch Neurol,2002,59(6):972-976.
[85]Butterfield DA,Reed T,Perluigi M,et al.Elevated pro,tein-bound levels of the lipid peroxidation product,4·hydroxy-2-nonenal,in brain from persons with mild cognitive impairment[J].Neurosci Lett,2006,397(3):170-173.
[86]Schipper HM,Bennett DA,Liberman A,et al.Glial heme oxygenase-1expression in Alzheimer disease and mild cognitive impairmen[J].Neurobiol Aging,2006,27(2):252-261.
[87]Yao Y,Clark CM,Trojanowski JQ,et al.Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment[J].Ann Neurol,2005,58(4):623-626.
[88]张大鹏,王奇,陈云波.阿尔茨海默病发病中淀粉样β蛋白的神经毒性作用[J].中国临床康复,2005,25(9):174-175.
[89]陈瑷,周玫.自由基医学[M].北京:人民军医出版社,1991.64-184.
[90]张铭湘,夏家辉.神经退化性疾病生物能量代谢和氧化应激研究进展[J].生命科学研究,2000,4(4)295-301
[91]王金兰,李建章等.缬沙坦对慢性脑缺血大鼠认知障碍及MDA、SOD的影响[J].实用神经疾病杂志,2005,(8):37-39.
[92]Brosnan MJ,Hamilton CA,et al.Irbesartan lowers superoxide levels and increases nitric oxide bioavaiability in blood vessels from spontaneously hypertensive stroke-prone rats[J].Hypertens,2002,20(2):281-286.
[93]Tanaka K,Wada N,Ogawa N.Chronic cerebral hypoperfusion induces transient reversible monoaminegic changes in the rat brain[J].Neurochem Res,2000,25:313.
[94]吕泽平,谢海群,郑陈光等.老年轻度认知障碍患者海马萎缩的MRI定量测定[J].脑与神经疾病杂志,2003,11(4):239、240.
[95]Killiany RJ,Hyman BT,Gomea-Isla T,etal.MRI measurements of entorhianl cortex vs hippocampus in preclinical AD[J].Neurology,2002,58:l188.
[96]刘树良,李坤成,王蕊等.轻度认知障碍者MR体积测量内颞叶结构对照研究[J].临床放射学杂志,2004,23(10):916-918.
[97]Devanand DP,Pradhaban G,Liu X,et al.Hippocampal and entorhinalatrophy in mild cognitive impairment:prediction of Alzheimer disease[J].Neurology, 2007,68(11):828-836.
[98]Jack CR,PeterSen RC,Xu YC,et al.Prediction of AD with MRIbased hippocampal volume in mild cognitive impairmen[J].Neurology 1999;52(7):1397-1403.
[99]Jack CR,Petersen RC,Xu YC,et al.Rates of hippocampalatrophy correlate with change in clinical status in aging and AD[J].Neurology,2000,55(4):484-489.
[100]Du AT,Schuff N,Amend D,et al.Magnetic resonanceimaging of the entorhinal cortex and hippocampus in mild cog-nitive imDamnent and Alzheimer's disease[J].Neurol Neuro-surg Psychiatry,2001,71(4):441-447.
[101]Kawamata T,Akiguchi I,Yagj H,et al.Neuropathologicalstudv on strains of senescence-accelerated mice(SAM)withage-related deficits in learning and memory[J].Exp Gerontol,1997,32(1-2):161-169.
[102]Hou IJ,Qiao DC.Current status of studying brain-derivedneurotrophic factor[J].Chin J Rehabil Med 2005;20(12):940-942.
[103]Hansson E,Ronnback L.Astrocytes in glutamate neurotmns-mission[J].FASEB J 1995;9(5):343-350.
[104]Hatten ME,Liem RK,Shelanski ML.Astroglia in CNS in-jury[J].Glia 1991;4(2):233-243.
[105]Sng H,Stevens CF,Cage FH.Astroglia induces neurogene-sis from adult neural stem cells[J].Nature 2002;417(6884):39-44.
[106]侯莉娟,乔德才.脑源性神经营养因子的研究现状[J].中国康复医学杂志,2005,20(12):940-942.
[107]Feldman H,Schehens P,Scarpini E,et al.Behavioralsymptoms in mild cognitive impairment[J].Neurology,2004,62:1199-1201.
[108]杨丽,宁宪嘉,程焱.老年普遍性脑萎缩轻微认知障碍相关因素的研究[J].中华老年心脑血管病杂志,2002,4(4):239-240.
[109]Bartres-FazD,Junque C,Clemenle IC,etal.MRI and lates of cognitive function in elders with memory impairment[J].Neurobiol Aging,2001,22:449-459.
[110]Hilis AE,Barker PB,Beauchamp NJ,et al.MR perfusion imaging rebeals regions of hypoper fusion associated with aphasia and neglect[J].Neurology,2000,55(6):782-788.
[111]Nanri M,Watanabe H.Availability of 2VO rats as a model for chronic cerebrovascular disease[J].Nippon Yakurigaku Zasshi,1999,113(2):85-95.
[112]刘汇波,叶翠飞,李斌,等.双侧颈总动脉结扎对大鼠学习记忆功能和海马组织形态学的影响[J].基础医学与临床,1998,18(4):54-58.
[113]Kogure D,Matsuda H,Ohnishi T,et al.Longitudinal evaluation ofearly Alzheimer's disease using brain perfusion SPECT.J Nucl Med,2000,41(7):1155-1162.
[114]Jellinger KA.The pathology of ischemic-vasculardementia:an update[J].J Neurol Sci,2002,203-204:153-157.
[115]Encinas M,Juan R,Marcos A,et al.Regional cerebral blood flowassessed with“Tc-ECD SPET as a marker of progression of mildcogni'ti've l'mpm'rment to Alzheimer's disease.Eur J Nucl Med MolImaging,2003,30(11):1473-1480.
[116]Hirao K,Ohnishi T,Hirata Y,et al.The prediction of rapidconversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT.Neuroimage,2005,28(4):1014-1021.
[117]Staffen J,Schonauer U,Zauner H,et al.Brain perfusion SPECTin patient s wit h mild cognitive impairment and Alzheimer's dis2ease:comparison of a semiquantitative and a visual evaluation.JNeural Transm,2006,113(2):195-203.
[118]Okamura N,Arai H,Maruyama M,et al.Combined analysis of CSFTau levels and iodoamphetamine SPECT in mitd cognitiveimpairment:implications for a novel predictor of Alzheimer's disease.Am J Psychiatry,2002,159(3):474-476.
[119]Huang C,Wahlund LO,Almkvist O,et al.Voxel and VoI-basedanalysis of SPECT CBF in relation to clinical and psychologicalheterogeneity of mild cognitive impairment.Neuroimaging,2003,19(3):1137-1144.
[120]Wolf H,Jelic V,Gertz HJ,et al.A critical discussion of the role of neuroimaging in mild cognitive impairment.Acta Neurol Scand Suppl,2003,179:52
[121]Yoshiura T,Mihara F,Kuwanara Y,et al.MR relative cerebral flow mapping of Alzheimer's disease:correlation with Tc-99m HMPAO SPECT.Acad Radiol,2002,9(12):1383.
[122]Honda N,Machida K,Hosono M,et al.Interobserver variation in diagnosis of dementia by brain perfusion SPECT.Radiat Med 2002,20(6):281
[123]Nestor PJ,Fryer TD,Ikeda M,etal.Retrosplenial cortex(BA29/30)hypometabolism in mild cogtive impairment(prodromal Alzheimer's disease).Eur J Neurosci,2003,18(9):2663-2667.
[124]Drzezga A,Lautenschlager N,Siebner H,etal.Cerebral metabolic changes accompanying conversiom of mild cognitive impairment into Alzheimer's disease:a PRT follow-up study.Eur J Nucl Med Mol Imaging,2003,30(8):1104-1113.
[125]Mosconi L,Perani D,Sorbi S,etal.MCI conversiom to dementia and the APOE genotype:a prediction study with G-PET.Neurology,2004,63(12):2332-2340.
[126]Mosconi L,Perani D,Sorbi S,et al.MCI conversion to dementia and the APOE genotype.A prediction study with FDG PET.Neurology,2004,63(12):2332-2340.
[127]Arntiiz E,Jelic V,Almkvist O,et al.Impairment cerebral glucosemetabolism and cognitive functioning predict deterioration in mildcognitive impairment.Neuroreport,2001,12(4):851-855.
[128]Mosconi L.Brain glucose metabolism in the early andspecific diagnosis of Ahheimer,s disease.FDG-PETstudies in MCI and AD[J].Eur J Nucl Med MolImaging,2005,32:486-510.
[129]Petersen RC.Mild cognitive impairment:current research and Clinical lmplications.Seminars in Neurology.2007,27(l):22-31.
[130]Turner R,Le Bihen D,Moonen CT,et al.Echo-planar timecourse MIR of cat brain oxygenation changes.Magn ResonMed,1991,22(1):159-166.
[131]王荫华,白静,翁旭初,等.轻度认知障碍患者记忆力的功能磁共振研究[J].中国康复理论与实践,2004,10(3):132·135.
[132]王鲁宁.认知功能障碍的防治[J].中华内科杂志,2005;44(12):955-956.
[133]卢佩琳,陈炜.盐酸多奈哌齐治疗神经衰弱伴发认知障碍的临床研究[J].中国 老年保健医学,2008,6(4):29-30.
[134]姜长青,刘广义,郭宗君等.外源性雌激素对大鼠认知障碍的治疗作用[J].青岛大学医学院学报.2001,37(2):179-181.
[135]张晓春,左萍萍,葛秦生.雌激素类似药对去卵巢大鼠认知功能的影响[J].生殖医学杂志,2001,10(3):135-140.
[136]毕建忠,曹立军,许顺良等.植物雌激素对A1zheimerzs病模型大鼠认知障碍的干预作用[J].山东大学学报(医学版)2005,43(10):920-923.
[137]Shea TB,Rogers E.Folate quenches oxidative damage inbrains of apolipoprotein E-deficient mice:augrnent-ttation byvitamin E[J].Brain Res Mol Brain Res,2002,108(1-2):1-6.
[138]洪燕程义勇章广远,等.维生素B6缺乏对大鼠海马脑区氨基酸类和一氧化氮递质系统的影响[J].解放军医学杂志,2001,19:239-242.
[139]王金玉,侯一平,宋焱峰等.维生素B6对脑瘫幼鼠认知障碍和步态异常的改善作用[J].营养学报,2006,28(4):324-325.
[1]李浩,刘芳,徐立然,等.还脑益聪胶囊对老年轻度认知障碍的影响.中国中西医结合杂志,2004,24(8):689-693.
[2]李智杰,梅红彬.天地精丸治疗轻度认知障碍的临床研究.湖北中医杂志,2007,29(10):10-12.
[3]李浩,徐立然,罗增刚,等.还脑益聪合灯盏花素治疗轻度认知障碍临床研究.中西医结合心脑血管病杂志,2004,2(7):387-389.
[4]田金洲,朱爱华,钟剑,等.金思维治疗社区轻度认知损害老年患者记忆减退症状的1年随访.中国中药杂志,2003,28(10):987-99l。
[5]王健,张守琳,任玺洁.脑力宝改善老年人记忆功能障碍属肝肾阴虚证随机对照研.中国实验方剂学杂志,2002,8(2):48-50.
[6]龚康敏,郑源庞,王红裔,等.益脑冲剂治疗中老年认知功能减退45例临床观察.湖南中医杂志,1999,15(6):6-8.
[7]林庚庭,姚真敏,张俊杰.天地人口服液防治记忆障碍的实验及临床观察.辽宁中医杂志,1999,26(11):527-528.
[8]王学美,富宏,刘庚信,等.加味五子衍宗颗粒治疗轻度认知障碍的临床研究.中国中西医结合杂志,2004,24(5):392-395.
[9]何迎春,何烨,李谨,等.健脾填精方治疗轻度认知障碍21例疗效观察.新中医,2005,37(2):42-43.
[10]周如倩,林水淼,袁泉.参银口服液治疗轻度认知功能损害的临床研究中国中西医结合杂志,2007,27(9):793-795.
[11]钟剑,朱爱华,杨承芝,等.参乌胶囊治疗老年轻度认知损害临床对照研究.中国中药杂志,2007,32(17):1800-1803.
[12]郑卫莉,张杜平,刘莹.益气活血法治疗轻度认知功能障碍的临床研究.新疆中医药,2008,26(3):5-7.
[1]Petersen RC,Smith Waring SC,et al.Mild cognitive impairment clinical characterization and outcome[J].Arch Neurol,1999,56:303.
[2]Ronald C,Peterson RC.Mild cognitive impairment:Current Research and Clinical Impalication[J].Semin Neurol 2007,27(1):22-31.
[3]陈楷,陈可冀,周文泉,等.益智胶囊治疗老年血管性痴呆的临床研究[J].中国中西医结合杂志,1997,17(7):393-397.
[4]程薇薇,周文泉,陈楷,等.还聪丹胶囊治疗老年脑血管性痴呆的临床研究[J].中国中西医结合杂志,1998,18(2):81-84.
[5]赵琰,周文泉,高普,等.仙龙胶囊治疗血管性痴呆的临床研究[J].中国中西医结合杂志,1999,19(10):585-588.
[6]罗增刚,周文泉,高普,等.仙龙胶囊治疗血管性痴呆的临床观察[J].中国中西医结合杂志,2001,21(8):565-568.
[7]赵琰,周文泉,涂人顺,等.仙龙胶囊对小鼠学习记忆功能的影响[J].中国中医基础医学杂志,2000,6(6):24-27.
[8]中华医学会老年医学学会.中华医学会老年医学会对健康老年人标准的建议(修订草案,1995年)[J].中华老年医学杂志,1996,15(1):9.
[9]Petersen RC,Stevens JC,Ganguli M,et al.Practice parameter:early detection of dementia:mild cognitive impairment(an evidence-based review)[J].Neurology,2001,56:1133-1142.
[10]Peterson R C,Smith G E,Waring S C,et al.Mlid ccgnitiveimpairment:Clinical characterization and outcome[J].Arch Neuol,1999,56:303-308.
[11]Petersen RC,Doody R,Kurz A,et al.Current concepts in mild cognitive impairment[J].Arch Neural,2001,58:1985-1992.
[12]郑筱萸.中药新药临床研究指导原则.北京:中国医药科技出版社.2002:92-96.
[13]张明园.精神科评定量表手册[M].长沙:湖南科学技术出版社,1998:184-188.
[14]张明园.精神科评定量表手册[M].长沙:湖南科学技术出版社,1998:121-126.
[15]龚耀先.中国修订韦氏成人智力量表手册[M].长沙:湖南地图出版社,1992:35-59.
[16]张明园.精神科评定量表手册[M].长沙:湖南科学技术出版社,1998:166-168.
[17]杨承芝,钟剑,朱爱华,等.老年人轻度认知损害的中医证候研究[J].北京中医药大学学报(中医临床),2003,10(2):12-16.
[18]张雅萍,王兴臣,付强,等.轻度认知障碍中医证候流行病学研究[J].北京中医药大学学报,2007,30(10):709-712.
[19]唐洪梅,李锐,周莉玲,等.石菖蒲对中枢神经系统作用研究进展[J].广州中医药大学学报,2000,(2):21-24。
[20]徐江平,杨雪梅,等.中草药活性成分防治阿尔茨海默病的研究进展[J].第一军医大学学报,200l,(1):23-25。
[21]张旭静,曹奕丰,冯春红,等.川芎、当归对大鼠血栓形成的影响[J].中国临床药学杂志,2002,11(1):45-47
[22]张铭湘,夏家辉.神经退化性疾病生物能量代谢和氧化应激研究进展[J].生命科学研究,2000,4(4):295-301
[23]Hirose K,Chan PH.Blockade of glutamate excitotox-icity and its clinical applications[J].NeurochemRes,1993,18:479-483.
[24]富宏,王学美,刘庚信等.轻度认知障碍与氧自由基代谢和胆碱酯酶相关性的研究[J].中国老年学杂志,2004,24:17-18.
[25]沈维高,何欣,冯力民.大鼠在空间辨别性学习记忆时海马CA1,CA3区和DG的ACh能纤维和星形胶质细胞的变化.北华大学学报(自然科学版)[J],2006,7(3):224-231.
[26]Haba K,Ogawa N,Mieukawa K,et al.Time course of changes in lipid peroxidation,pre-and postsynaptic-cholinergic indices,NMDA receptor bindin and neuronal death in the gerbial hippocampus following transient ischemia[J].BrainRes,1991,560(1):116-212.
[27]O'Brein MD.The effect of M receptor on dementia[J].Dementia.1994,(5):133.