Treatment Of Alzheimer's Disease-under Scrutiny Of Evidence-based Medicine And Data Mining

This research selected Alzheimer' s disease- one of the mostchallenging and important health issues for the elders in the 21stcentury-as the subject to deal with. The rationale for this research ismainly six-fold: (1) Aging society is one of the major public health issue(2) the unmet need in aging society: to improve the quality of life ofthe elders (3) Alzheimer' s disease is one of the major health threatsto the elders in China (4)Many researches showed that the treatment effectof Traditional Chinese Medicine (TCM) is much better than WesternMedicine (5) If these treatment effects derived from various studies couldbe synthesized, that will be conducive to clinical decision-making. (6)Using two internationally- recognized research tools: meta analysis anddata mining to exp]ore Alzheimer' s treatment is an innovative way ofresearch on TCM, which will help TCM with internalization.The purpose of this research was mainly three-fold: to get anunderstanding of current researches conducted on Alzheimer' s disease inChina, to systematically evaluate and compare Alzheimer' s treatmentdelivered by TCM with that by Western Medicine and also conductquantitative analysis on qualified researches, to discover meaningfulhidden patterns of Chinese drug compatibility used for amnesia and/ordementias.This dissertation contains three parts, part one was literaturereview, part two and part three discussed Alzheimer' s disease mainly fromthe viewpoint of meta analysis and data mining, respectively. There werefour main topics reviewed in part one, including (1) The current advancesin evidence-based medicine (2) The current advances in data mining (3)Alzheimer' s disease-East meets West (4) Treatment of Alzheimer' sdisease based on invigoration if both Spleen and KidneyThe data source in meta-analysis of Alzheimer' s treatment came fromthe following two data base: cnki (http://www.cnki.net)and wanfangdata(http://www.wanfangdata.com.cn). Inclusion criteria were: (1) Chineseliterature (2) Published between year 1994 and year 2004 (3) Using TCMas treatment and Western Medicine as control (4) Similar research purposeand methodology (5) Subjects were diagnosed as Alzheimer' s disease (6)Objective outcome measurement (7) Being statistically able to besynthesized by meta-analysis Only 40 out of 2403 studies met the inclusion criteria. The other data source used in data mining experimentcame from Chinese Decoction data base. After using dementia or amnesiaas keyword, 197 decoctions were collected and processed for data mining.Findings in meta-analysis of Alzheimer' s treatment: From year 1997to year 2004, there were forty qualified studies. All in all, the studyquality deserved improving. Among those studies, there were three studieswithout giving patients' ages, five without marking days of treatment.For those studies with days of treatment, the treatment duration wasbetween 15 to 240 days. There was also one study without describing outcomemeasurement tool. In evaluating the treatment effects of chronic disease,short days of treatment possibly cannot warrant effective. When assessedby Jadad score, 7 out of 40 studies got a score of 2 points, 25 out of40 studies got 1 point, and the rest 8 studies scored zero. None of thesestudies obtained a Jadad score of more than 2. Especially, in blindingof the patients and the description of losses to follow-up items, only4 studies mentioned double-blinding and three mentioned single-blindingmethod. None described attrition. Regarding control groups, they cangenerally be categorized into three groups: cholinesterase inhibitor,intelligence booster and CNS stimulant and others. In cholinesteraseinhibitor control group, there were 4 studies using Donepezil as control.In intelligence booster and CNS stimulant group, there were 17 studiesusing Piracetam as control. These two drugs were the most frequently usedmedication in their own categories.Heterogeneity test showed statistically significant with P valueless than 0.0001, no matter odds ratio or risk difference was chosen asoutcome measurement. Radial plot revealed the following studies asoutliers: study 4, studyl4, studyl6, studyl9, study 26 and study 35.Sensitivity analysis also showed that study 14 was the largest sourceof heterogeneity.Finally, odds ratio were pooled using random effect model. The resultsshowed odds ratio=3.24, 95% confidence interval was between 2.30 and4.56.In order to explore possible sources of heterogeneity, subgroup analysis was also conducted by different control groups and publicationdate, respectively. The cutoff point for publication date was year 2002(included) and four different control groups, includingneurotransmitters, non-neurotransmitters, placebo and combined therapywere investigated. The results showed OR=4.76 with 95% confidenceinterval between 2.77 and 8.18 and OR=2.11 with 95% confidence interval between 1.59 and 2.78 for earlier publication and later publicationgroups, respectively. This implies that after year 2002, the advantageof Traditional Chinese Medicine is losing. Another subgroup analysis bydifferent control groups showed TCM was no better than neurotransmittersgroup with OR=1.2, 95% confidence interval between 0.73 and 1.97, whichwas statistically insignificant. However, TCM showed more advantageousthan non-neurotransmitters, placebo and combined therapy. Possibleexplanation for this finding is because the therapeutic effect ofCholinesterase inhibitors, the mainstream of current Alzheimer' stherapy, is generally better than neuro-protective approaches,therefore, when compared with TCM, there was no significant difference.Findings in data mining experiment on Alzheimer' s treatment:According to theories of TCM, there are even more approaches toAlzheimer' s treatment. The commonly used drugs covered many differentcategories. In decreasing order of frequency used, they are tonics, whichaccounted for 29% of total frequency, followed by tranquilizers, whichaccounted for 14.8% and antipyretics, which accounted for 10.3%. Thefrequently used drugs in tonics were Renshen, Danggui and Shudihuang. Intranquilizers category, they were Yuanzhi, Suanzaoren and Zhusha. Inantipyretics, they were Gancao, Dihuang and Huanglian. Overall, frequencydistribution for top 23 (=12.7%) prescription drugs, in decreasingorder of frequency, were Renshen, Yuanzhi, Fushen, Fuling, Danggui,Gancao, Shudihuang, Suanzaoren, Maidong, Shichangpu, Zhusha, Wuweizi,Hungqi, Gui, Baiziren, Sangjisheng, Shengdi, Longgu, Chuanniuxi, Shanyao,Tusizi, Tiandong and Fangfeng.They were generally with sweet flavor, except for Yuanzhi andShichangpu which were pungent and bitter in taste. There were no drugsof extremely cold character. The drugs of cold character were Zhusha,Shengdi and Tiandong; the drugs of slightly cold character were Gancaoand Maidong; the drugs of mild nature were Fushen, Fuling, Suanzaoren,Baiziren, Sangjisheng, Longgu, Chuanniuxi and Shanyao; the drugs oflukewarm character were Renshen, Yuanzhi, Shudihuang, Hungqi, Tusizi andFangfeng; the drugs of warm character were Danggui, Wuweizi and Shichangpu;Only Gui belong to drug of extremely warm character. Regarding channeltropism, all drugs' therapeutic effects can cover heart, liver, spleen,stomach, lung and kidney channels, but mainly on heart, kidney and spleenchannels. All drugs except Shudihuang, nungqi, Chuanniuxi,Shanyao, Sangjisheng, Tusizi, Tiandong, and Fangfeng could havetherapeutic effects on heart channel. Only Gancao, Maidong, Shichangpu,Shengdi and Tiandong could be distributed to stomach channel. Most ofthese frequently used drugs belong to tonics and tranquilizers. Among them, 9 drugs belong to tonics and 5 drugs belong to tranquilizers.Association rule mining section showed the following mostfrequently used associations, in decreasing order of transaction, were:Fuling(?)Yuanzhi, Fushen(?)Yuanzhi, Fuling(?)Renshen, Shichangpu(?)Yuanzhi, Shudihuang(?) Yuanzhi, Suanzaoren(?)Yuanzhi,Suanzaoren(?)Renshen. This implies that the major component of drugcompatibility went to tranquilizers, especially Suanzaoren and Yuanzhi.Inferring from the above association rules, TCM mostly treat Alzheimer' sdisease as a kind of heart disease. Because based upon one TCM theory:the heart dominates all mental activities.In factor analysis section, Kaiser' s criteria were applied todrop factors whose eigenvalues less than one and four factors wereretained. The cumulative percentage of the total variation in thevariables accounted for by these four factors amounted to 68.4%. The firstfactor included Tusizi, Chuanniuxi, Wuweizi, Shudihuang, Baiziren andShanyao. The second factor included Gui, Suanzaoren, Shengdi, Fangfengand Shichangpu. The third factor included Hungqi, Sangjisheng, Renshenand Gancao. The fourth factor included Tiandong, Maidong, Yuanzhi andFushen.Five clusters were determined in cluster analysis section. However,the maximum average silhouette equaled to 0.05, indicating no substantialstructure had been found.Finally, in multidimensional scaling section, the results showedno obvious clustering but the goodness-of-fit in 3 dimensional model isacceptable.