阿尔茨海默病证候级联假说探讨
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摘要
阿尔茨海默病(AD)是β淀粉样蛋白(Aβ)级联反应在临床上表现的一个连续谱,即从无症状的临床前期到有症状的轻度认知损害(极早期)和痴呆(早期、中期、晚期),与中医证候表现的正邪消长特征十分相似。根据临床调查、统计分析等结果进行逻辑推理,认为AD进展期间中医证候演变并非"髓减""痰盛""瘀血""火盛""胃衰"等无序的单一证候,而是有时间顺序的证候级联,即"启动于肾虚,进展于痰瘀火,恶化于毒盛虚极",反映了AD发生、发展、恶化的规律,为制订AD治疗策略提供了理论依据,也有助于为AD证候演变进行个性化预警。
Alzheimer's disease(AD) is a continuous spectrum of the clinical manifestations that reflect the beta amyloid(Aβ) cascade in the brain,that is,from the asymptomatic pre-clinical stage to the symptomatic mild cognitive impairment(very early stage) and dementia(early,middle and late stage),which are very similar to the characteristics of the wax and wane of the healthy qi and pathogenic qi manifestations of traditional Chinese medicine(TCM)patterns. According to the results of clinical investigation and statistical analysis,it is concluded that the evolution of TCM patterns during AD progression is not a disordered single pattern such as "brain marrow reduction","phlegm excess","blood stasis","internal fire excess"and"stomach failure",but a cascade of patterns with certain time sequence,i. e. "initiated from kidney deficiency,progressed with phlegm and blood stasis fire and deteriorated with toxic excess and deficiency extreme". It is the pattern cascade hypothesis that reflects the regular patterns of occurrence,development and deterioration of AD,which also provides a theoretical basis for the formulation of AD treatment strategies,and helps to carry out personalized early warning for the evolution of AD patterns.
Alzheimer's disease(AD) is a continuous spectrum of the clinical manifestations that reflect the beta amyloid(Aβ) cascade in the brain,that is,from the asymptomatic pre-clinical stage to the symptomatic mild cognitive impairment(very early stage) and dementia(early,middle and late stage),which are very similar to the characteristics of the wax and wane of the healthy qi and pathogenic qi manifestations of traditional Chinese medicine(TCM)patterns. According to the results of clinical investigation and statistical analysis,it is concluded that the evolution of TCM patterns during AD progression is not a disordered single pattern such as "brain marrow reduction","phlegm excess","blood stasis","internal fire excess"and"stomach failure",but a cascade of patterns with certain time sequence,i. e. "initiated from kidney deficiency,progressed with phlegm and blood stasis fire and deteriorated with toxic excess and deficiency extreme". It is the pattern cascade hypothesis that reflects the regular patterns of occurrence,development and deterioration of AD,which also provides a theoretical basis for the formulation of AD treatment strategies,and helps to carry out personalized early warning for the evolution of AD patterns.
引文
[1]PRINCE M,COMAS-HERRERA A,KNAPP M,et al.World Alzheimer report 2016[R/OL].(2016-09-20)[2018-09-21]. https://www. alz. co. uk/research/world-report-2016.
[2]KELLEY AS,MCGARRY K,GORGES R,et al. The burden of health care costs for patients with dementia in the last 5 years of life[J]. Ann Intern Med,2015,163(10):729-736.
[3]ALLSOP D,LANDON M,KIDD M. The isolation and amino acid composition of senile plaque core protein[J].Brain Res,1983,259(2):348-352.
[4]GOLDMAN DP,FILLIT H,NEUMANN P. Accelerating alzheimer's disease drug innovations from the research pipeline to patients[J]. Alzheimers Dement,2018,14(6):833-836.
[5]HARDY J,ALLSOP D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease[J]. Trends Pharmacol Sci,1991,12(10):383-388.
[6]KITAGUCHI N,TAKAHASHI Y,TOKUSHIMA Y,et al.Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity[J]. Nature,1988,331(6156):530-532.
[7]KARCH CM,CRUCHAGA C,GOATE AM. Alzheimer's disease genetics:from the bench to the clinic[J]. Neuron,2014,83(1):11-26.
[8]CAO X,SDHOF TC. A transcriptionally[correction of transcriptively]active complex of APP with Fe65 and histone acetyltransferase Tip60[J]. Science, 2001, 293(5527):115-120.
[9]苗迎春,田金洲,时晶,等.遗忘型轻度认知损害患者认知功能与中医证候的相关性[J].中西医结合学报,2009,7(3):205-211.
[10]高胤桐,田金洲,时晶,等.轻度认知损害证候分布特征文献研究[J].中医杂志,2017,58(17):1503-1506.
[11]田金洲.王永炎院士查房实录[M].北京:人民卫生出版社,2015:99-100.
[12]倪敬年,时晶,魏明清,等.中药临床试验中的痴呆分期及辨证标准[J].中华中医药杂志,2017,32(2):452-454.
[13]陈淑慧,陈耀龙,杨志敏,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].世界中医药,2007,2(2):81-83.
[14]时晶,倪敬年,魏明清,等.阿尔茨海默病证候变化与认知结局的关联性[J].北京中医药大学学报,2017,44(4):339-343.
[15]EWERS M,SPERLING RA,KLUNK WE,et al. Neuroimaging markers for the prediction and early diagnosis of alzheimer's disease dementia[J]. Trends Neurosci,2011,34(8):430-442.
[16]田金洲,时晶,阿尔茨海默病中医诊疗联合共识小组.阿尔茨海默病的中医诊疗共识[J].中国中西医结合杂志,2018,38(5):523-529.
[2]KELLEY AS,MCGARRY K,GORGES R,et al. The burden of health care costs for patients with dementia in the last 5 years of life[J]. Ann Intern Med,2015,163(10):729-736.
[3]ALLSOP D,LANDON M,KIDD M. The isolation and amino acid composition of senile plaque core protein[J].Brain Res,1983,259(2):348-352.
[4]GOLDMAN DP,FILLIT H,NEUMANN P. Accelerating alzheimer's disease drug innovations from the research pipeline to patients[J]. Alzheimers Dement,2018,14(6):833-836.
[5]HARDY J,ALLSOP D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease[J]. Trends Pharmacol Sci,1991,12(10):383-388.
[6]KITAGUCHI N,TAKAHASHI Y,TOKUSHIMA Y,et al.Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity[J]. Nature,1988,331(6156):530-532.
[7]KARCH CM,CRUCHAGA C,GOATE AM. Alzheimer's disease genetics:from the bench to the clinic[J]. Neuron,2014,83(1):11-26.
[8]CAO X,SDHOF TC. A transcriptionally[correction of transcriptively]active complex of APP with Fe65 and histone acetyltransferase Tip60[J]. Science, 2001, 293(5527):115-120.
[9]苗迎春,田金洲,时晶,等.遗忘型轻度认知损害患者认知功能与中医证候的相关性[J].中西医结合学报,2009,7(3):205-211.
[10]高胤桐,田金洲,时晶,等.轻度认知损害证候分布特征文献研究[J].中医杂志,2017,58(17):1503-1506.
[11]田金洲.王永炎院士查房实录[M].北京:人民卫生出版社,2015:99-100.
[12]倪敬年,时晶,魏明清,等.中药临床试验中的痴呆分期及辨证标准[J].中华中医药杂志,2017,32(2):452-454.
[13]陈淑慧,陈耀龙,杨志敏,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].世界中医药,2007,2(2):81-83.
[14]时晶,倪敬年,魏明清,等.阿尔茨海默病证候变化与认知结局的关联性[J].北京中医药大学学报,2017,44(4):339-343.
[15]EWERS M,SPERLING RA,KLUNK WE,et al. Neuroimaging markers for the prediction and early diagnosis of alzheimer's disease dementia[J]. Trends Neurosci,2011,34(8):430-442.
[16]田金洲,时晶,阿尔茨海默病中医诊疗联合共识小组.阿尔茨海默病的中医诊疗共识[J].中国中西医结合杂志,2018,38(5):523-529.