Study On Diagnosis And Treatment Of Senile Dementia Based On Syndrome Differentiation Of Deficiency And Excess And Assessment Of Risk Factors Of Brain Aging

Objective:1)To determine the main points of TCM syndrome differentiation of senile dementia,to summarize the core drugs that Jingqing Hu researcher treats senile dementia based on syndrome differentiation,and to verify their effectiveness and mechanism of action through experimental research,so as to provide the basis for TCM syndrome differentiation and treatment of comprehensive treatment.2)To develop assessment methods and intervention measures for risk factors of brain aging,combine them with syndrome differentiation of deficiency and deficiency of traditional Chinese medicine,develop comprehensive diagnosis and treatment plan for senile dementia,explore the effectiveness and practicability of diagnosis and treatment plan through qualitative research method of narrative medicine,and provide new ideas for diagnosis and treatment means of senile dementia.Methods:1)Main points of syndrome differentiation of senile dementia:The diagnostic criteria of "five deficiency and five deficiency"(namely,deficiency of essence,deficiency of Yin,deficiency of Yang,deficiency of qi,deficiency of blood,stagnation of qi,phlegm and dampness,blood stasis,fire and Fufeng)were analyzed,and the syndrome differentiation pool of "Five deficiency and five deficiency" was determined according to the literature analysis results.On this basis,the Expert Consultation Questionnaire for Selection of syndrome differentiation items of Five deficiency and five deficiency was formulated to collect the opinions of experts in related fields.Then the core working group of this subject summarized and sorted out the expert opinions and discussed,and finally determined the main points of syndrome differentiation of "five deficiency and five reality".2)Discovery and effectiveness verification of core drugs for the treatment of Alzheimer’s disease from the perspective of vanity and reality:Select senile dementia patients who were treated in the outpatient department of geriatrics of Jingqing Hu researcher in Guang ’anmen Hospital from September 2020 to December 2022,and use the cloud platform of ancient and modern medical records to analyze the deficiency syndromes of traditional Chinese medicine,the frequency and efficacy of traditional Chinese medicine,the complex network of traditional Chinese medicine,and the association analysis of deficiency syndromes with traditional Chinese medicine.In summary,Jingqing Hu researcher discussed the core drugs for treating senile dementia from the point of absence and reality.3)Experimental research:The 3-month-old male APP/PS1 double transgenic mice were used as the model animal of Alzheimer’s disease,and the non-transgenic C57BL/6J mice with the same genetic background were used as the blank control group.The APP/PS1 double transgenic mice were divided into high,medium and low dose Jinxuananmai groups,Dingzhi wan group,Dingzhi Wan+Jinxuananmai group and positive drug control group.The blank control group was only given normal saline intragastric administration.After 40 days of intervention,Morris water maze method was used to observe the changes of behavior and learning and memory ability of each group of mice.Plaque(SP)deposition in the hippocampus of mice in each group was detected by Congo red staining.The morphology and quantity of nissellite in hippocampus of mice were observed by Nissellite staining.The morphological and quantitative changes of microglia(Iba1)and neurons(NeuN)in the hippocampus of mice in each group were observed by immunofluorescence labeling.The differences of cell nuclei,mitochondria,synaptic gap width and other organelles and ultrastructure in hippocampal area of mice in each group were observed by transmission electron microscopy,and the pathological changes were compared among the groups.The changes of APP,Aβ1-42,SNX27 and other proteins related to pathological changes of Alzheimer’s disease were detected by Western Blot.Neuroinflammatory cytokines(TNF-α,IL-6,IL-10),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected by Elisa,and neuroinflammatory and oxidative stress effects were observed.The senescence of mice cells in each group was observed by β-galactosidase staining.4)Develop a diagnosis and treatment plan for senile dementia based on syndrome differentiation of deficiency and deficiency and assessment of risk factors of brain aging:On the basis of previous studies on the key points of syndrome differentiation of senile dementia,literature research,data investigation,expert interview and other methods are used to explore the risk factors of brain aging in senile dementia and corresponding treatment methods,so as to clarify the integrated diagnosis and treatment plan of traditional Chinese and Western medicine for senile dementia.5)Preliminary study on the application of diagnosis and treatment plan:Through the qualitative research method of narrative medicine,parallel medical records of patients with senile dementia were established to record the patients’ daily implementation of the comprehensive treatment program,subjective feelings after the application of the program,measurement results of various objective indicators and observation indicators.They included the simple mental State Checklist(MMSE),the Activity of daily Living scale(ADL),the Quality of Life Scale for Alzheimer’s patients(QOL-AD),and the burden of Care scale(Zarit).Keep tracking for 6 months,and record the changes of observation indicators in 0,3 and 6 months.The efficacy and practicability of diagnosis and treatment plan were preliminarily evaluated by narrating the improvement of symptoms of patients and their family members and comparing before and after each objective index measurement.Results:1)The main points of syndrome differentiation were hearing loss,eyesight loss,hair turning white or falling off,teeth loosening and falling off,waist and knee soreness and so on.The main points of Yin deficiency syndrome differentiation are emaciation,hot flush,hot hands and feet,night sweats,oropharyngeal dryness.Yang deficiency syndrome differentiation points for complexion white,chills,hand,foot and not temperature,god exhausted,loose stool,etc.The main points of syndrome differentiation of Qi deficiency are spontaneous sweating,exhaustion,fatigue,shortness of breath,low voice and so on.The main points of blood deficiency syndrome differentiation are pale complexion,pale eyelid,pale claw nail,pale mouth and lip,dizziness,etc.The main points of syndrome differentiation of Qi stagnation are emotional depression,impatience and irritability,happy sighing,chest,flank,abdomen and back distension and pain,pain is not fixed,when light and heavy,symptom changes are related to emotion,etc.The main points of syndrome differentiation of phlegm-dampness syndrome are excessive secretion of skin oil(sticky sweat,facial oil),heavy body,abdominal fullness,abdominal fullness,wet pubic area,etc.The main points of syndrome differentiation of blood stasis are swarthy complexion,skin nail fault,fixed pain location or pain such as acupuncture,local lump,dark lip color,etc.The main points of syndrome differentiation are fear of heat,red face,constipation,local redness and heat pain(gingival,sore throat,oral ulcer,etc.),irritability,etc.The main points of syndrome differentiation of Fufeng syndrome are autoimmune disease history,gastrointestinal irritability,allergic reaction,skin scratches(+).2)Jingqing Hu researcher was included in 58 effective medical cases of treating senile dementia from the perspective of false and real,with a total of 286 consultations and 286 prescriptions,covering 136 flavors of drugs,with a total frequency of 3982 medications.The most frequently used drugs were poria(80.42%),calamus(75.52%)and forsythia(69.93%).The most common deficiency syndrome was Jing deficiency syndrome(75.52%),and the most common demonstration was hot syndrome(60.84%).The correlation analysis of syndrome and traditional Chinese medicine showed that the core prescriptions of essence deficiency syndrome were calamus,poria codonopsis,Radix codonopsis and Radix polygonatum(Dingzhi Wan).The core prescriptions for obtaining hot syndrome are honeysuckle,scrophulariae,angelica,licorice,forsythia and knotweed(Jin Hyun Anmai Fang).3)Morris water maze results showed that both Jinxuan Anmai Recipe and Dingzhi Wan could reduce the latency of APP/PS1 mice,increase the number of platform crossing and target quadrant residence time.Western Blot results showed that Jinxuan Anmai Fang and Dingzhi Wan could increase the content of SNX27 in hippocampal tissue of mice,and reduce the expression of Aβ1-42 and APP.The Elisa results showed that Jinxuan Anmai Fang and Dingzhi Wan could increase the content of anti-inflammatory factor IL-10,reduce the expression of TNF-α,IL-6 and other pro-inflammatory factors in the hippocampus of AD mice,increase the content of antioxidant GSH-Px and SOD,and reduce the content of oxidation end product MDA.β-galactosidase staining showed that the number of senile cells in brain tissue of APP/PS1 mice decreased after the intervention of Jinxuananmai prescription and Dingzhi Wan.Congo red staining results showed that the amount of SP in brain tissue of APP/PS1 mice decreased after the intervention of Jinxuan Anmai Fang and Dingzhi Wan.Immunofluorescence experiment results showed that the amount of NeuN increased and the amount of Iba1 decreased in brain tissue of APP/PS1 mice after the intervention of Jinxuan Anmai prescription and Dingzhi Wan.4)The deficiency and deficiency syndrome differentiation scale of senile dementia was established,and the evaluation methods and corresponding intervention measures of brain aging risk factors including aging,genetic factors,history of cardiovascular and cerebrovascular diseases,chronic inflammation,history of head trauma,history of toxin exposure,mental health,immune/infectious diseases,lack of neurohormones,obesity,sleep problems,adverse lifestyle and other 12 aspects were established.The process of making individualized diagnosis and treatment plan for senile dementia patients has been drawn up.Parallel medical records of 9 patients with senile dementia who had been treated with this treatment scheme for 6 months were recorded by narrative medicine qualitative research method.It was found that after 6 months of comprehensive treatment scheme,patients’ MMSE scale score was improved overall,but the difference was not statistically significant(P>0.05).The scores of ADL scale and Zarit scale were decreased,and the difference was statistically significant(both P<0.05).QOL-AD scale score increased,the difference was statistically significant(P<0.01).Conclusions:1)According to researcher Jingqing Hu,the commonly used prescriptions for the treatment of Alzheimer’s disease are Jinxuan Anmai Fang and Dingzhi Wan.The experiments have proved that both of them can improve the memory of dementia mice,inhibit the abnormal deposition of Aβ,the loss of neurons and other pathological changes,reduce the inflammatory reaction and oxidative stress reaction of cerebral nerve,and have the effect of improving the symptoms of dementia and inhibiting the progression of key pathological links.2)The diagnosis and treatment plan for senile dementia based on syndrome differentiation and brain aging risk factor assessment can improve the cognitive ability of senile dementia patients to a certain extent,improve their quality of life and mental state,reduce the risk of brain aging,and reduce the burden of caregivers,and its effectiveness and practicality have been preliminarily verified.