摘要
痴呆是由于脑功能障碍而产生的获得性智能损害综合症。随着我国人口的老龄化,老年期痴呆的发病率有升高趋势,已成为一个日益突出的社会及医学问题,为此,寻求痴呆的治疗,对改善老年人的生活质量尤为重要,在治疗方面,由于痴呆是器质性病变,绝大多数是不可逆的,所以目前尚无满意的疗效,针对痴呆本质上的治疗仍在努力的探索之中,有些原因所致的痴呆试验性药物治疗取得了一些可喜的进展,药物治疗有改善部分症状的作用。与此同时,中医药治疗痴呆具有巨大的潜力,总结和发掘中药的有效成分,建立统一的疗效观察指标和定量疗效评定的药理模型,在攻克痴呆中为人类提供新的希望。因此,进行中西医结合治疗痴呆是迫切需要研究的课题,我们探讨了中西医结合治疗老年性痴呆的临床疗效。中医药是我国的瑰宝,在目前老年期痴呆的治疗尚未有特异疗效的情况下,相比之下,中医药在延缓衰老以及衰老相关疾病的防治方面有着丰富的理论和实践经验,具有潜在的优势和广阔的开发前景。研究发现雌激素对女性认知功能有保护作用,设计了雌激素对女性阿尔茨海默病患者的对照观察的研究,提出了雌激素配合胆碱酯酶抑制剂治疗女性阿尔茨海默病患者的可能性,也取得了理想的效果,达到了改善老年期痴呆认知功能的预期目的,为女性阿尔茨海默病患者的治疗带了了福音。本文通过对痴呆的中西医结合治疗与康复观察研究,发现其有较好的疗效。总之寻找确切有效的防治方法,改善和提高患者的生存质量和对社会的适应能力,以最大程度减少痴呆类疾病所带来的不良后果,都有十分重要的意义。本文在认真研究国内外近期对痴呆的发病机制与治疗研究的基础上,以中西医结合施治与康复为主导思想,运用中医的特点,结合西医的作用,配合康复治疗,对痴呆,尤其是阿尔茨海默病和血管性痴呆进行预防、控制与治疗,取得了明显的疗效。
首先提出并开展了中药提纯针剂(络泰)治疗老年期痴呆(本文主要指血管性痴呆和阿尔茨海默病痴呆)的疗效研究。不管血管性痴呆还是老年性痴呆(阿尔茨海默病),脑血流量的减少可能是共同的病理改变,而络泰的有效成分人参皂苷R1,且其是无菌冻干粉剂,有较高的稳定性。本课题的动物实验表明人参总皂甙对大鼠脑缺血再灌注损伤有明显的保护作用,表现在它可扩张血管,增加脑血流量,减轻脑水肿超微结构损伤和降低死亡率。其保护作用与抑制钙积累密切相关。临床应用证明它具有
扩张心脑血管,增加心脑血管流量,改善心脑微循环,并对脑缺血后海马CAI区(与学习和记忆有关)的迟发性神经元损伤有明显的保护作用,且又抗炎作用和雌激素样作用, 临床实践证明,人参皂苷具有与雌激素相似的改善记忆和神经保护作用。雌激素参与中枢神经系统功能的调节,内源性雌激素是Alzheimer Disease(AD), 的保护因素,雌激素替代治疗对AD的预防和治疗有益。因此,人参皂苷作为具有雌激素样作用的中药,可以作为雌激素的替代品,对于AD的防治具有重 要意义。在动物衰老过程中,钙代谢平衡失调造成神经元中游离钙超负荷,使神经元可塑性减低,从而发生记忆障碍。李麟仙研究表明,同样人参皂苷的益智作用机制之一即它的有效成分中的Rb1能够降低细胞内钙的浓度及钙蛋白的活性。缩小脑梗死范围,从而有抗AD和Vascular Dementia(VD)作用。
其次,研究了中草药治疗血管性痴呆的效果,方药组成为:黄芪、红花、枸杞子、五味子、赤芍、川芎、红花、当归、地龙。方中黄芪、红花、枸杞子、五味子可益气补肾,填精生髓;赤芍、川芎、红花、当归活血化瘀,地龙疏通经络。现代药理研究证明,黄芪、五味子、枸杞子对神经系统有兴奋作用,能改善人的智能活动;当归、川芎、赤芍、红花、五味子、黄柏均有不同程度的钙通道阻滞作用,可明显增加脑血流量,改善脑循环,清除自由基。地龙,赤芍含有纤维蛋白溶解酶激活物,有溶栓作用,绞股蓝抗衰老。所以以上诸药配伍可以提高患者血中超氧化物歧化酶的活性,降低过氧化脂质,抗自由基损伤,改善脑微循环,促进神经细胞功能恢复,并对脑缺血后海马CAI区(与学习和记忆有关)的迟发性神经元损伤有明显的保护作用,进一步延缓了痴呆的发生,为众多的血管性痴呆患者提供了价廉的治疗渠道。
第三,提出并开展了从中草药千层塔中的提取物—石杉碱甲(胆碱酯酶抑制剂)配合雌激素治疗阿尔茨海默病的可行性,这和美国Research Nurse Coordinator Alzheimer's Disease Research Center(Houston Baylor College of Medicine)目前几个重点研究阿尔茨海默病的研究机构,观察雌激素治疗阿尔茨海默病的研究几乎同步进行。流行病学证明,女性阿尔茨海默病的发病率远远高于男性,其可能的原因之一是因为雌激素水平的下降有关。雌激素对认知等有保护作用已达共识,本课题的研究表明:雌激素配合石杉碱甲治疗阿尔茨海默病对其认知功能等有保护作用,并且可加强石杉碱甲的疗效,为女性阿尔茨海默病的预防及治疗带来了希望。同时还小样本的采用了安理申配合雌激素治疗阿尔茨海默病的试验,取得了和国外同类研究的一致性。
康复研究在老年期痴呆的治疗中起着举足轻重的作用。由于痴呆是一种慢性疾病
且社会生活功能缺损日益加重,需要对其进行照料,而我国的国情决定了多数患者是在家庭内被照料,照料负担极?
Dementia is a disease of acquired intelligence injury syndrome, caused by brain dysfunction. The incidence rate of Senile Dementia has been inclining to climb up, along with aging population. This has been an outstanding problem of society and medical science. Dementia therapy is a key point of improving the life quality of the aged. Dementia is a parenchymal disease, mostly irreversible. No satisfying therapy has been developed and those aimed to entity is still under research. Some promising progresses have been made in tentative drug treatment to several kinds of causations, some of whose symptoms are ameliorated. At the same time, traditional Chinese medicine (TCM) possesses great potential to fight against Dementia. Hopes lay in summarizing and uncovering effective components, and the creation of unitive pharmacody model, including observing guidelines and quantitative evaluation of effects. Therefore, applying the combination of TCM and west medicine to Dementia therapy is an urgent topic and we discussed its clinical effects. In comparison to west medicine, TCM, the gem of our country, has accumulated rich theories and practical experiences in postponing senility, and prevention and cure of the related diseases. Thus, TCM has great potential and bright prospect to be developed. Investigations revealed that estrin protects female cognitive function. We designed contrast researches to observe how estrin affects female patients with Alzheimer’s Disease (AD), suggested the possibility of cholinesterase inhibitor copulated with estrin for cure, and reached the objective of ameliorating cognitive function of Senile Dementia sufferers. This article found promising effects of the combination of TCM and west medicine to Dementia therapy by observing research of treatment and rehabilitation. In short, finding operative ways of prevention and cure, ameliorating and improving the patients’ life quality and ability to adapting the society, and lessening dysresults of Dementia, do possess great significance.
First of all, we researched the effects of using LuoTai(络泰)to treat Senile Dementia which means Vascular Dementia and Alzheimer’s Disease here. Vascular Dementia and Senile Dementia (AD) probably share the same symptom of brain blood flow decrease. The effective component of LuoTai is ginsenoside R1, which is sterile dongganfenji, characterized with high stability. Experiments showed that ginsenoside can obviously protect rat brain from ischemia reperfusion injury, by dilating blood vessel, enhancing
blood flow, ameliorating ultrastructure injury of brain edema, and decreasing death rate. This protective function is closely related to the accumulation of calcium. Clinical application proved its ability of dilating blood vessels, enhancing blood flow, ameliorating microcirculation, evidently preventing late neur injury of hippocamp’s CAI domain(related to study and memory) after brain ischemia, and resisting inflammation thus resisting AD and VD.
Clinical practic also certified that ginseng is an effective TCM to prevent and cure AD Its active component ginsenoside has similar effects as estrin to ameliorate memory and protect nerve. Estrin takes part in central nervous system control, and intrinsic estrin is a protective factor of AD, and its replacement therapy is beneficial to the prevention and cure of AD. So, as a kind of TCM that having the same function of estrin, ginsenoside can be applied as a replacement of estrin and is important to prevent and cure of AD. During the course of animal aging, disturbance of calcium metabolism causes overload of free calcium in neuron, reduces neuron’s compliance, and then obstructs memory. Li Linxian ‘s research made clear that one of the mechanisms of improving intelligence is in virtue of the effective component Rb1’s ability to reduce [Ca2+]i and calcium protein activity, and cerebral infarction domain decrease.
Next, we researched the effects of using TCM to treat Vascular Dementia. The researched prescription is: mongolian milkvetch root, safflower, barb
引文
Cummings JL,Benson DF, Dementia---A clinical Approach. Boston: Butterworths, 1983:36-56
王维治主编.神经病学[M],第四版.北京:人民卫生出版社, 2002:248-260.
美国精神病学会.郑延平,赵靖平译精神障碍诊断统计手册.第三版修订本(DSM-III-R).国外医学 精神病学分册,1987,(140):5-721
许贤豪.老年期痴呆的诊断[J].中华神经科杂志,2003,36(1):70-71
高素荣,袁锦楣主编.痴呆诊疗学[M].北京:北京科技出版社, 1998:1-30
Mahler ME, Cummings JL,Benson DF.Treatable dementia.West J Med, 1987: 140:5-721
Zhang ZX,Gustavo CGC,Hong Z, etal. Prevalence of dementia and major subtypes in four cities of Nothern and Southern. 2000,58(Supply13):A102.
张振馨,魏镜,洪霞,等.北京市城乡痴呆及其主要亚型的患病率[J].中华神经科杂志, 2001,34(4):199-203
屈秋民,乔晋,杨剑波,等.西安地区中老年人的痴呆患病率调查[J]. 中华老年医学杂志, 2001,20(4):283-286
陈昌惠,沈渔,高素荣,张力平.906名60岁以上老年人的痴呆调查[J]. 中华老年, 1989,8:75-78
Lobo A,launer LJ, Fratiglion L, etal. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based. cohorts. Neurology. 2000, 54(Supply15):S 4-9.
张洪泉,余新文.中华抗衰老医药学[M].北京:科学出版社,2000:1510-1511
Ueda K, Kawano H, Hasuo Y, etal. Prevalence and etiology of dementia in a Japanese commumity.stroke,1992,23:798-803
Tatemichi TK ,Desmond .Mayeux R, et al . Dementia after stroke: baseline frequency, risks, and clinical feature in hospitalized cohort . Neurology,1992,42(6):1185～1193
Hachinski V. Preventable senility : a call for action against the vascular dementias .
Lancet, 1992,340(8820):645～647
谭铭勋.血管性痴呆[J].国外医学脑血管疾病分册,1994,3(2):79～81
朱江南,许宏伟,张新媛.阿尔茨海默病的治疗与心理沟通.中国临床康复,2003,7(16):2350-2351
张明园,聂光亚,王红争,等. 痴呆和Alzheimer病的发病率研究[J].中华医学杂志,1990,70:424
阎芳,李淑然.老年期痴呆的发病率与预后[J].临床精神医学杂志2001, 11(1):41-43
余金龙,冯容妹,方少心,等.广东省沿海地区农村老年期痴呆的患病率调查[J].中国神经精神疾病杂志,1998,1:30-32.
张明园,Robert Kblzman,陈佩俊,等.痴呆和阿尔茨海默病的发病率[J].中华精神科杂志, 1998,31(4):195-198.
Boothby H, Blizar R, Livingstorn G, etal. The gospel oak study stage III: the incidence of dementia. Psychol Med,1994,24:89-95.
Letenner L,Jacqmin H, Commenges D, etal. Cerebral and functionl aging: first results on Prevalence and incidence of the Paquid cohort. Methods Int Med, 1993.32:249-251.
Bickel H, Cooper B. incidence and relative risk of dementia in an urban elderly population: findings of prosective field study. Psychol Med,1994,24:179-192
邵福源,黄流清. Alzheimer 病治疗研究的现状与展望[J].医学服究, 2002,2(3):137-140.
Sala SD, Francescani A, Muggias S, etal. Variables linked to psychotic symptos in Alzheimer disease.Eur.J Neurol,1998,5(6):553-560.
Feldman H, Caregiver burden an important concept in the management of Alzheimer disease. Alzheimer Insights,1995,5(4):1-3.
Munoz DG, Canaparthy CR, Elinsziw M, etal. Educationl attainment and socioeconomic status of patients with autopsy –confirmend Alzheimer disease.Arch Neurol,2000,57(1):85-89.
Fratiglioni L, Viitanen M, von Strauss E, et al. Very old women at highest risk of dementia and Alzheimer’s disease: Incidence data from the Kungshol men Project, Stockholm. Neurol 1997: 48 :132-8.
Corder EH, Saundres AM, Strittmatter WJ,etal. Applipoprotein E, Surveval in
Alzheimer’s disease patients, and competing risk of death and Alzheimer’s disease. Neurology, 1995,45:1323
Skoog I. Arterial hypertension and Alzheimer′s disease. In: Leys D, Pasquier F, Scheltens Ph. Stroke and Alzheimer′s Disease. Hague: Holland Academic Graphics, 1998.89-100.
中华医学会神经病学分会.钱采韻,吕传真,王新德执笔.血管性痴呆诊断标准草案[J].中华神经科杂志,2002,35(4):246
王新德,陈海波,蔡晓杰等.老年人脑血管性痴呆的研究[J].中华老年医学杂志, 1992,11(3):138-141.
潘永惠,赵庆杰,段淑荣.阿尔茨海默病与血管性痴呆的临床及相关检查特点分析[J].中国现代医学杂志,2003,6:66-70
Li YM,Xu M,Laimt, etal. Photo a CT ivatedg-secreta inhibitors directed to the actives it ecovalently label presenilin1. Nature, 2000,405(67-87): 689-694
Esler WP, Kimberly WT, Ostaszewski BL,etal. Transition state analogue inhibitors of secreta seblinds directly to presenilin1. Nature cell.2(7):428-434
Delacourte A, David JP, Sergeant N, etal. The biochemical pathway of neuro fIbrilary degeneration in aging and Alzheimer’s disease. Neurology, 1999,52(6):1158-1165
Marie TH. Alzheimer’s disease: Plaque removers and shakes. Nature, 2000,406(67-95):465
高曲文,陈俊抛,田时雨,等.β-淀粉样蛋白诱导脑内细胞凋亡及褪黑素的保护作用[J].中华神经科杂志,2000,33:7-9
Bullido MJ, Aldudo J, Frank A, etal.A polymer phism in the tau gene associated with risk for Alzheimer’s disease.Neuro sci lett,2000,278:49-52
Andreasen N, Minthon L, Clarberg A,etal. Sensitivity, specificity, and stability of CSF-Tau in AD in community based patients ample. Neurology, 1999,53:1488-1494
刘辉,陈俊抛.Alzheimer病与NO/NOS[J].国外医学·神经病学神经外科学分册, 1999,26:75-77
Ohgoh M, Shimizu H, Ogura H, etal. A strogelial trophic support and neuronal cell death: influence of cellula renergy level on type of cell death induced by mitochondrial toxin in cultured by mitochondrial toxin in drial toxin in cultured rat cortical neurons.J Neuro Chem,2000,75:925-933
Iijima K, Ando K, Takeda S, etal.Neuron-specific phosphoryl at ion of Alzheimer’s beta-amyloid precursor protein by cycl in depend end kinase 5[J]. Neurochem, 2000, 75(3):1085-1091
Kessler J, Mielke R, Grond M, etal. Front all tasks do not reflect front all function in patients with probable Alzheimer’s disease. Int Neuro sci, 104(1-4): 1-15
Waring SC, Rocca WA, Petersen RC, etal. Post-menopausal estrogen replacement therapy and risk of AD: a population based study.Neurology,1999,52:965-970
DrsmondDW, Moronby JT, Paik MC, etal.Prequency and clinical determinants of dementia after ischemic stroke[J].Neurology,2000,54(101):1124-1131
廖小平.无症状脑梗死预后[J].中国实用内科杂志.2001,21(11): 648
贾志荣,高素荣. 脑梗死痴呆影响因素调查的临床研究[J].临床神经病学杂志, 1992, 5(4):216
Corblick PB, Roman C, Maconb CA. Vascular dementia[A]// Corblick PB,Altbr MA.Handbook of Neumepidemialogy[M].New York:Marcel Dekker,1994:197-214
Corbuck PB.Status of risk factor Vascular dementia associated with stroke[J]1997, 28(2):459-463
Hbndbrson AS. Dementia [M]. Ceneva: World Health Organization,1994,9-26 6Lindsay,hbbbrt R, Pockwood K. The Canadian study of health and aging: risk of Vascular dementia [J].Stroke, 1997,28(3):526-530
Lindsay,hbbbrt R, Pockwood K. The Canadian study of health and aging: risk of Vascular dementia [J].Stroke,1997,28(3):526-530
Prisoni M, Ancblo D, Blanchbtti N, etal Association of Apalipaprapralein with Vascular dementia[J].JMAM,1994,27(17):1317
柳太云 多梗塞痴呆和Alzheimer型痴呆认知功能与局部脑血流的关系[J].中国临床心理学杂志,1997,5(3):155
王静淑.延缓衰老从瘀论治[J].中国中医基础医学杂志,1998,4(8):48
陶国枢.现代老年医学新进展[M].北京:科学技术出版社,1997,269
郭洪志,梁临萍,杨望清. AD脑脊Tau蛋白指标改变[J].脑与神经疾病杂志, 2003,1:11-13
Shoji M, maisubara E, Kanai M,et al.J Neurol Sci,1998,158(2):134
丁强,左谦,丁铭臣等. 痴呆患者脑脊液胆碱酯酶活性初步研究. 北京医学, 1992;14(5):262
沈正萱.Alzheimer s病和胆碱酯酶.生理科学进展,1993;24(4):302)
杨柏灿,刘仁人. Alzheimer型痴呆的中医证型研究[J].上海中医药杂志, 2000,34(4):12-14
何建成.老年性痴呆中医药治疗五法[J].中医药学报,1999,27(2):3
钟振国,张凤芬.浅谈老年性痴呆的治疗[J].广西中医药,2000,24(4):1-3
颜乾麟.老年期痴呆精神行为障碍辨治探讨[J].上海中医药杂志,2000, 34(4):15-16
吴正治,张永锋.清肝泻火法对老年痴呆模型学习记忆及中枢单胺神经递质的影响[J].中国中医基础医学杂志,1998,4(12):25-28
杨柏灿,刘仁人.Alzheimer型痴呆的中医证型研究[J].上海中医药杂志, 2000,34(4):12-14
何建成.老年性痴呆中医药治疗五法[J].中医药学报,1999,27(2):3
李贵.中药复方防治老年期痴呆的药理学研究概况.中草药,1999;10:26
郑晓瑛,蒲继红.老年性痴呆的辨治举隅[J].新中医,2000,32(3):56
李求兵,梅嵘.老年痴呆症的中西医诊断与治疗[M].北京:中国医药科技出版社, 1997,56.
Schonknecht, Panrel J,Schroder J. Quantitative magnetic resonance tomography in diagnosis of Alzheimer’s dementia. Z Geronntol Geriatr. 20001,34(2):101-107
Jack CR, Petersen RC, Xu YC.Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology.1999,52(7):1397-1403
Kirsch SJ, Jacobs RW,,Butcher L, et al. Prolongation of magnetic resonance T2 time inhippocampus of human patients marks the presence and severity of Alzheimer disease. Neurosci Lett,1992;152:1257-1260
Kinkel WR, Jacobs L, Polachini, et al. Subcortical arteriosclerotic encephalopathy (Binswanger’s disease): a vascular computed tomographic,nuclear magnetic,and clinical correlations. Arch Neurol, 1985,42:951-959
Liu CK, Miller BL, Commings JL, et al. A quantitative MRI study of vascular dementia. Neurology.1992; 42:138-143
陈湛,娄海燕,张秀侠,等.脑梗死早期智能障碍与脑影像学改变关系分析.中国神经精
神疾病杂志,2000,26(1):33～36
Hunt AL, Orrison WW, Yeo RA, et al. Clinical significance of MRI matter lesions in the elderly. Neurology.1998,3:138-143
Sarangi S, San pedro EC, Mountz JM, Antrior choroidal arter infarction presenting as aprogressive cognitive deficit. Clin Nucl Med 2000,25(3):187-190
Soininen HS, Scheltens P. Early diagnosis indices for the prevention of Alzheimer’s disease. Ann Med, 1998,30(6):553
Tohgi H, Yonezawa H, Takahashi S, et al. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer’s type and vascular dementia with deep white matter changes. Neuroradiology, 1998,40(3):131
Scheltens P, Launer LJ, Barkhof F, et al. The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO single-photon-emission computed tomography for the dignosis of Alzheimer disease in a community-dwelling elderly population. Alzheimer Dis Assoc Disord, 1997,11(2):63
Mielke R, Heiss WD. Positron emission tomography for diagnosis of Alzheimer’s disease and vascular dementia. J Neural Transm Suppl, 1988,53 (2):227
Sachdev P, Gaur R, Brodaty H, etal.Longitudinal study of cerebral blood flow in Alzheimer’s disease using single photon emission computed tomography. Psychiatry Res,1997,68:133 135.
Pietrini P, Furey ML, Alexander GE, et al. Association between brain functional failure and dementia severity in Alzheimer’s disease: resting versus stimulation PET study. Am J Psychiatry, 1999,156 (3): 470
Ibanez V, Pietrini P, Alexander GE, et al. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer’s disease. Neurology, 1998, 50(6): 1585
Catalan MJ, Ishii K, Honda M, et al. A PET study of sequential finger movements of varying length in patients with parkinson’s disease. Brain, 1999, 122(3): 483
李彪,朱承谟,张冀先,等 脑SPECT显像和rCBF测定在早老性和多发性脑梗塞性痴呆的临床应用 中华核医学杂志,1993,13:78 80
李德鹏,马云川,苏玉盛,等.老年性痴呆与血管性痴呆的18F-FDGPET显像分析[J].中风与神经疾病杂志,2001,18(4):213-214.
Scheltens P, Launer LJ, Barkhof F, et al. The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO single-photon-emission computed tomography for the dignosis of Alzheimer disease in a community-dwelling elderly population. Alzheimer Dis Assoc Disord, 1997,11(2):63
Pietrini P, Furey ML, Alexander GE, et al. Association between brain functional failure and dementia severity in Alzheimer’s disease: resting versus stimulation PET study. Am J Psychiatry, 1999,156 (3): 470
llsop D, Twyman LJ, Davies Y, etal.Modulation of β- amyloid precursor protein and fibrilar tangle. In Oneill C, Anderton B,eds. Neuronal sign altrans ductionand Alzheimer disease. [M].London: Portla and press, 2001,1-14.
Wasco W, Tanzi RE. Etiological clues from gene defect scausing early onset familial Alzheimer disease.In:Wasco W, Tanzi RE, eds. Molecular mechanisms of dementia [M]. Totowa: Human a Press,1997.1-20.
童坦君,张宗玉.基因的不稳定性与老年痴呆发病机制.见:陈可冀,主编.跨世纪脑科学-老年性痴呆发病的机制与诊治[M].北京:北京医科大学中国协和医科大学联合出版社,1998.40-43.
张均田.老年痴呆的发病机制及治疗策略.见:张均田,主编.神经药理学研究进展[M].北京:人民卫生出版社,2002.16-29.
Howlett DR,Perry AE,Godifrey F, etal. Inhabition of fibril for mation in beta amyroidpeptide by a novel series of benzo furans[J]. J biochem,1999,340(pt1):283-289
Skoog I. Arterial hypertension and Alzheimer′s disease. In: Leys D, Pasquier F, Scheltens Ph. Stroke and Alzheimer′s Disease. Hague: Holland Academic Graphics, 1998.89-100.
Jobst KA, Smith AD, Barker CS, et al. Association of atrophy of medial temporal lobe with reduced blood flow in patients with a clinical and pathological diagnosis of Alzheimer’s disease.J Neurol Neurosurg Psychiatry,1992,55:190-194.
de la Torre JC. Hemodynamic consequences of deformed microvessels in the brain in Alzheimer′s disease. Ann N Y Acad Sci, 1997, 826:75-91.
Mattson MP, Engle MG, Rychlik B. Effects of elevated intracellular calcium levels on the cytoskeleton and tau in cultured human cortical neurons. Mol Chem Neuropathol,
1991, 15:117-142.
Zarow C, Zaias B, Lyness SA, et al. Cerebral amyloid angiopathy in Alzheimer disease is associated with apolipoprotein E4 and cortical neuron loss. Alzheimer Dis Assoc Disord, 1999,13:1-8.
De la Torre JC. Critical threshold cerebral hypoperfusion causes Alzheimer′s disease? Acta Neuropathol (Berl), 1999, 98:1-8.
Banati RB, Gehrmann J, Wiessner C, Hossmann KA, Kreutzberg GW. Glial expression of the beta-amyloid precursor protein (APP) in global ischemia. J Cereb Blood Flow Metab, 1995, 15 :647-654.
Dorheim MA, Tracey WR, Pollock JS,et al. Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer′s disease. Biochem Biophys Res Commun, 1994, 205:659-665.
Buee L, Hof PR, Bouras C, et al. Pathological alterations of the cerebral microvasculature in Alzheimer′s disease and related dementing disorders. Acta Neuropathol (Berl), 1994, 87:469-480.
Bartenstein P, Minoshima S, Hirsch C, et al. Quantitative assessment of cerebral blood flow in patients with Alzheimer′s disease by SPECT. J Nucl Med, 1997, 38:1095-1101.
Hatanpaa K, Chandrasekaran K, Brady DR, et al. No association between Alzheimer plaques and decreased levels of cytochrome oxidase subunit mRNA, a marker of neuronal energy metabolism. Brain Res Mol Brain Res, 1998, 59:13-21.
Simpson IA, Chundu KR, Davies-Hill T, et al. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer′s disease. Ann Neurol, 1994, 35 546-551.
Franceschi M, Alberoni M,Bressi S,etal.Correlations between cognitive impairment, middle cerebralartery flow velocity and cortical glucose metabolismin the early phase of Alzheimer'sdisease[J]. Dementia, 1995,6:32-38
de la Torre JC. Hemodynamic consequences of deformed microvessels in the brain in Alzheimer′s disease. Ann N Y Acad Sci, 1997, 826:75-91.
Mattson MP, Engle MG, Rychlik B. Effects of elevated intracellular calcium levels on the cytoskeleton and tau in cultured human cortical neurons. Mol Chem Neuropathol,
1991, 15:117-142.
Harkins SW, Taylor JR, Mattay VS. Response to tacrine in patients with dementia of the Alzheimer′s type: cerebral perfusion change is related to change in mental status. Int J Neurosci, 1996, 84:149-156.
Tune L, Brandt J, Frost JJ, et al. Physostigmine in Alzheimer′s disease: effects on cognitive functioning, cerebral glucose metabolism analyzed by positron emission tomography and cerebral blood flow analyzed by single photon emission tomography. Acta Psychiatr Scand Suppl,1991,366:61-65.
Tsukada H, Kakiuchi T, Ando I, et al. Functional activation of cerebral blood flow abolished by scopolamine is reversed by cognitive enhancers associated with cholinesterase inhibition: a positron emission tomography study in unanesthetized monkeys. J Pharmacol Exp Ther, 1997,281:1408-1414.
蔡永春,李凤文,张立石.补肾活血方对衰老小鼠学习记忆的功能[J].中国中医基础医学杂志,1998;17(3):133-5
阎勤.滋肾活血汤治疗老年性痴呆64例[J].陕西中医,1998;19(1):15
陆建原,马静,黄青松.脑力康口服液对老年痴呆动物模型学习?记忆及某些中枢神经递质的影响[J].陕西中医学院学报,1993;21(3):38-9
Overstreet DH.Memory enhance-mentin animal sand human follow in gad ministration o f cholinergic agents. Psychology.1989;31(1):23 cholinergic neurone
Perry EK,Perry RII,Blessed G,etal.Necroposy evidence of central cholinergic deficits in senile dementia. Lancet 1997;1:189-194.
徐江平,刘传缋.中枢烟碱受体与阿尔茨海默病[J].中国药理学通报, 1995;11(1):9
钟毅,孙立,朱秉匡 脾肾两虚夹瘀夹痰理论与衰老机理探讨[J].中医杂志, 2000,41(6):325
韩向明,周宣轩,杨文明,等 寿星宝对脑组织蛋白质及核酸代谢的影响[J].中国中医基础医学杂志,1999,5(1):36
龚跃新,孙立,项晓人,等.四君子汤对衰老小鼠肝和大脑皮质的影响的透射电镜观察[J].中国中西医结合杂志,1995,15(6):359
王彩霞,李德新 滋补脾胃法治疗痴呆大白鼠脂质过氧化损伤的实验研究 中国中
医基础医学杂志,2000,6(2):28
俞征宙,陈文华,俞立年,等.从增龄对本虚标实证的影响探讨中医衰老机理[J].中国中西医结合杂志,1992,12(2):80
于俊生.略论痰瘀之间的相互转化关系[J].辽宁中医杂志,1994,21(6):247
王静淑.延缓衰老从瘀论治[J].中国中医基础医学杂志,1998,4(8):48
张伯礼.血瘀证与活血化瘀[M].北京:学苑出版社,1970, 767
陶国枢.现代老年医学新进展[M].北京:科学技术出版社,1997,269
Marks SJ, Batra RR, Frishman WH. Estrogen replacement therapy for cognitive benefits:viable treatment or forgettable “senior moment”? Heart Dis 2002; 4(1):26-32.
Thomas T. A role of hormone in the primary prevention of Alzheimer’s disease. Climacteric 2001; 4(2):102-9.
Fillit HM,The role of hormone replacement therapy in the prevention of Alzheimer’s disease. Arch Intern Med 2002;162(17):1934-42.
许贤豪,主编.神经免疫学[M].武汉:湖北科学技术出版社,2000.327-333.
Woolley CS, McEwen BS, J. neurology 1993,336:293-306.
Singh M, Meyen EM,Milard WJ,Simpkins JW.Brain Res, 1994,644:305-312.
Ersher WB. J Am Geriatr soc.1993,41:176-181.
Belfort MA, Saade GR,Snabes M,etal. Am J Obstet Gynecol.1995, 172:1273-1278.
Perry EK, Perry RII,Blessed G,etal.Necroposy evidence of central cholinergic deficits in senile dementia Labcet,1997,1:189-194.
Davis KL, Pollak WR,Pitney WP,etal.Cholenergic markers in elderly patients with early signs of Alzhermer’s disease.
Zandi PP, Carlson MC, Plassman BL, et al. hormone replacement therapy and incidence of Alzhermer’s disease in older Women: the Cache County Study. JAMA 2002, 288(17):2123-2129.
Gibbs RB. Effects of Estrogen on basal forebrain cholinergic neurons vary as function of dose and duration of treatment. Brain Res 1997,757(1):10-16
Zandi PP, Carlson MC, Plassman BL, et al. hormone replacement therapy and incidence of Alzhermer’s disease in older Women: the Cache County Study. JAMA 2002, 288(17): 2123-2129
Lon SS, Martin R,Farlow,etal.Effects of estrogen replacement therapy on respone to tacrine in Patients with Alzheimer’s disease.Neurology,1996, 46:1580.
Gibbs RB. Effects of Estrogen on basal forebrain cholinergic neurons vary as function of dose and duration of treatment. Brain Res 1997,757(1):10-16.
Rogers SL, Farlow MR,Doody RS,etal.A 24-week,double blinded, lacebo-controlled trial of donepezil in patients with Alzheimer’s Disease. Neurology,1998,50:136-145.
Li HN, Min QY. Report on 30 patients in blood vessel dementia of improving cognition with Huperizine. Xandai kangfu (Modern Rehabil) 2001;5(4):59.
Jia Z, Sun M, Gu FS, et al. Estradiol replacement therapy post-menopausal women with or without coronary artery disease. Chinese Journal of Cardiology 1999,27(5):346-348.
Goldsmith HS. Omental transposition to the brain for Alzheimer′s disease. Ann N Y Acad Sci,1997, 826:323-336.
Hachinski VC, Lassenn NA, Marshall J. et al. Multi infarct dementia a cause of mental deteriorate in the elderly[J]. Lancet,1994,11:207-209
Moreney JT, Bagiella E, Tatemichi TK, et al.Dmentia after stroke increases the risk of long term stroke recur end [J].Neurology,1997,48:1317-1325.
Tatemichi K, Desmend DW,Paik M. et al.Clinical determinants of dementia related to stroke[J].Ann Neurol,1993,33:568-575.
Tatemichi TK, Paik M,Bagiella E, et al. Risk of dementia after stroke in a hospitalized cohort :results of longitudinal study[J]. Neurology,1994,44: 1885-1891.
Roman GC, Tatemichi TK, Erkiniuntt T, et al. Vascular dementia:diagnostic criteria for research studies[J]. Neurology,1993,43:250-260.
Terayama Y, Meyer J, Kawamura J. et al. Patters of cerebral hypoper fusion compared among demented and nondemented patients with stroke[J]. Stroke, 1992,23:686-692.
Bousser MG, Tournier L, Asserve E.Summary of the first international workshop on CADASIL[J]. Stroke, 1994,25:704-707.
Ducros A, Nagy T, Alamowitch S, et al. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen koph alopathy, genetic homogeneity and mapping of the locus with in a 2 cm interval [J].Am J Humgenet 1996, 58:171-181.
Loeb C, Gandolfo F,Bino G.Intellectual impairment and cerebral lesion sin multiple
cerebral infarcts.A clinical computed tomography study[J]. Stroke,1998,19:560-565.
Laakso MP, Partanen K, Riekkinen P, et al.Hippocampal volumes in Alzheimer disease, Parkinson disease with and without detementia,and in vascular detementia: an MRI study[J]. Neurology,1996,46:678-681.
Henono H, Durien I,Lucas C, et al. Detementia in stroke[J]. Neurology, 1996,47:852-853.
Jeffvictorof F. Multi center clinical pathological correlation detementia[J]. Am J Psychiatry, 1995, 152:1476-1484.
Tapiola T, Lehtovirta M, Ramnerg J, et al.CSF Tau is related to appolipoproteine gene type in early Alzheimer disease proteic [J].Neurology,1998,50:169-174.
Katzman R, Zhang MY,Chen PJ, et al. Effccts of appolipoproteine on dementia and aging in the Shanghai survey of dementia[J]. Neurology, 1997,49:779-785.
Rubinsztein DC. Apolipoproteine. A review of its roles in lipoproteine tab olism, neuronalgro with and repair and ASA risk factor for Alzheimer disease[J]. Psychol Med, 1995,25:223-229.
Oan J, Lanser BK, Zijerreld I, et al. Detementia in hereditaty cerebral hemorrhage with amyloidosis Dutch type[J].Arch Neurol, 1990,47:965-967.
吴子明,彭建龙.益智灵冲剂对实验性老年痴呆病理模型的作用[J].中西医结合杂志, 1992,12(10):622
荒木五朗.从临床角度看阿耳茨海莫型老年痴呆[J].国外医学,中医中药分册, 1991,13(4):261
董桂英,赵世珂,郭立华.补肾活血法治疗老年期痴呆临床观察[J].中医药研究, 1997,13(5):13
彭萌.补肾开窍汤治疗老年痴呆16例[J].湖北中医杂志,1997,19(5):19
段从存,王怀印.补肾健脑汤为主治疗老年性痴呆症30例[J].安徽中医学院学报, 1994,(3):28
刘宝珍.地黄益脑汤配合光量子血疗治疗老年性痴呆30例[J].广西中医药,1994,17(5):10
孙明江,张守志.银杏叶制剂治疗老年性痴呆的药理基础及应用研究[J].山东中医药大学学报,1998,22(3):221-223
顾正中.脑循环与临床[M].上海:上海科学技术出版社,1982:50
Frackowiakr SJ, Pozzilli C, Legg J, et al. Regional cerebral oxygen supply and utilization in dementia: A clinical and physiology study with oxygen-15 and position tomography[J]. Brain, 1981,104:753
Obrien JT, Eagger S, Eytedg MS, et al. A study of rCBF and cognitive performance in Alzheimer disease[J]. J Neurol Neurosurg psychiatry, 1992,55(10):1182
Rogers RI. Decreased cerebral blood flow precedes multi infarct dementia but follows senile dementia of Alzheime type[J]. Neurology, 1986,36:1
Meyer JS. Cognition and cerebral blood flow fluctuate together in multi-infarct dementia [J].Stroke,1988,19:163
Kitagawa Y. Ctcbf correlations CT-CBF Correlations of cognitive deficits in in multi-infarct dementia [J].Stroke, 1984,15:1000
平井俊策 基底核异常与痴呆[J].日本医学介绍,1987,8(10):454.
傅仁杰.老年痴呆病证的诊断?辨证分型及疗效评定标准[J].中医杂志,1991,32(2)56.
王新德.脑血管疾病分类(1995)[J].中国实用内科杂志,1997,17(5):312-315
高贤均.中草药钙通道阻滞剂的研究与展望.中西医结合杂志,1990,(7):447
阴键,郭力弓.中药现代研究与临床(1).第一版,北京:学苑出版社1993:114-353.
杨莘,王玲.老年性痴呆病人情感障碍的护理[J].中华护理杂志,2001,(1):37.
刘道宽,左及.Alzheimer病的病理生化和药物治疗进展[J].临床神经病学杂志, 1998,11(3):188.
Hasegawa K. The study on the brief intelligence scale for dementia elderly. Seichinigaku (psychiatry), 1974,16:956.