Traditional Chinese medicine composition for mild cognitive impairment as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for mild cognitive impairment as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 5 to 20 parts of wine-processed rhizoma polygonati, 2 to 10 parts of rhizoma dioscoreae, 2 to 10 parts of poria cocos, 1 to 5 parts of cortex cinnamomi, 2 to 10 parts of fructus alpiniae oxyphyllae and 1 to 5 parts of radix ginseng. On the other hand, the invention discloses the traditional Chinese medicine composition extract which is obtained through water decoction extraction. The traditional Chinese medicine composition provided by the invention has the application of treating mild cognitive impairment, is mainly used for treating mild cognitive impairment caused by yang-deficiency constitution, and can be used for tonifying kidney and marrow, replenishing essence and tonifying qi.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for mild cognitive impairment, and a preparation method and application thereof. Background Art

[0002] Mild cognitive impairment (MCI) is a clinical state between normal aging and mild dementia. MCI as a disease concept was first proposed by Petersen et al. in 1999 and was officially recognized by the Quality Standards Subcommittee of the American Academy Neurology. It is generally believed that MCI refers to the clinical phenomenon of mild memory impairment and / or mild other cognitive impairment in the elderly, which is not enough to diagnose dementia. At present, there is no clear disease entity, but it is widely believed to be a clinical entity or clinical symptom group between normal aging and mild dementia. Studies have shown that about 10% to 12% of MCI are converted to clinical Alzheimer's disease (AD) each year, while only 1% to 2% of the normal elderly population develops AD each year. Therefore, the MCI population is considered to be a high-risk group for dementia. Mild cognitive impairment is a group of people with obvious memory impairment or mild other cognitive impairment, but it does not affect daily life, and is a clinical state between normal aging and mild dementia. Early and active intervention for MCI can improve or delay cognitive impairment and even the development of dementia. According to domestic reports, the conversion rate of mild cognitive impairment to dementia within 3 years is about 39.2%, and the monthly expenses of dementia patients in China account for about 40.3% of their family income.

[0003] In epidemiology, MCI represents a wide range of cognitive states with varying degrees, in addition to normal cognition and dementia. It can be caused by any cause, and the condition can improve, stabilize, or progress to complete dementia. MCI is a clinical state between normal aging and dementia. It is mainly manifested by the patient's memory loss that is not commensurate with age (typical memory loss). Other mild cognitive impairments may also occur, but they are not enough to affect the patient's social and work functions, and do not meet the diagnostic criteria for dementia. Its core symptom is cognitive impairment. Depending on the cause or location of the damage, it can involve one or more functional impairments such as memory, language, executive function, and structural skills. Depending on whether the patient has cognitive impairment in the field of memory, MCI is divided into two categories: amnestic MCI and non-amnestic MCI. As a transitional stage between normal aging and dementia, MCI is the most active part of early dementia diagnosis research, and it provides a "window of opportunity" for the prevention and treatment of dementia. In addition, compared with irreversible dementia with an incidence rate of 1%, MCI with an incidence rate of about 14% is more meaningful for prevention and intervention, and plays an important role in early intervention in the dementia "window period" and promoting successful aging.

[0004] Since amnestic mild cognitive impairment is considered to be the prodromal stage of Alzheimer's disease, the current intervention strategies of Western medicine mostly follow the treatment plan for Alzheimer's disease. There are mainly drugs that improve brain tissue blood supply and brain cell metabolism. Commonly used drugs include ginkgo biloba extract, amitriptyline mesylate rhobasin tablets (Du Ke Xi), γ-aminobutyric acid (GABA) derivatives and nucleoside derivatives (Nuo Fu Kang, Citicoline). This type of drug has a positive effect on improving cognitive function and has become the first choice for clinical treatment of patients with mild cognitive impairment. Drugs that improve neurotransmitter transmission include cholinesterase inhibitors such as donepezil hydrochloride (Aricept) and rivastigmine bitartrate (Exelon) and Huperzine A (Haberine or Shuangyiping) extracted from the Chinese herbal medicine Thousand Layer Tower developed by my country. At present, the efficacy of this type of drug for patients with mild cognitive impairment is still in progress. Existing research results are inconsistent. 3 Antioxidant and anti-inflammatory drugs Oxidative damage and inflammation play an important role in neurodegenerative diseases and brain aging changes. Currently, there are antioxidant drugs (selegiline) that reduce the production of free radicals, free radical scavengers (vitamin E) and non-steroidal anti-inflammatory drugs (naproxen). The effect of these drugs on improving cognitive dysfunction is still uncertain. 4 Estrogen replacement therapy is controversial because of the risk of cardiovascular and cerebrovascular diseases and cancer.

[0005] In addition, according to a number of domestic studies, acupuncture and Chinese herbal compound nootropics can improve the cognitive function, dementia and self-care ability of patients with mild to moderate Alzheimer's disease, and have a positive intervention effect on cognitive dysfunction, but its specific mechanism is unclear and more case data are needed to prove it. There is also a lack of formal clinical trials of Chinese medicine that are effective in treating mild cognitive dysfunction. Summary of the invention

[0006] In view of the above technical problems, the present invention provides a Chinese medicine composition for mild cognitive impairment, and a preparation method and application thereof.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is:

[0008] On the one hand, the present invention provides a traditional Chinese medicine composition for treating and / or alleviating mild cognitive impairment. The traditional Chinese medicine composition comprises, by weight, 5-20 parts of Polygonatum odoratum, 2-10 parts of yam, 2-10 parts of Poria cocos, 1-5 parts of cinnamon bark, 2-10 parts of Alpinia oxyphylla and 1-5 parts of ginseng.

[0009] As a preferred embodiment, the Chinese medicine composition comprises, by weight, 10-20 parts of Polygonatum sibiricum, 5-10 parts of yam, 3-8 parts of Poria cocos, 1-3 parts of cinnamon bark, 3-8 parts of Alpinia oxyphylla and 1-3 parts of ginseng;

[0010] Preferably, in parts by weight, the Chinese medicine composition comprises 15 parts of Polygonatum odoratum, 7.5 parts of yam, 5 parts of Poria cocos, 1.5 parts of cinnamon bark, 5 parts of Alpinia oxyphylla and 1.5 parts of ginseng.

[0011] On the other hand, the present invention provides a traditional Chinese medicine composition for treating and / or alleviating mild cognitive impairment, which comprises, by weight, 5-20 parts of Polygonatum sibiricum extract, 2-10 parts of yam extract, 2-10 parts of Poria cocos extract, 1-5 parts of cinnamon extract, 2-10 parts of Alpinia oxyphylla extract and 1-5 parts of ginseng extract.

[0012] As a preferred embodiment, the Chinese medicine composition comprises, by weight, 10-20 parts of Polygonatum sibiricum extract, 5-10 parts of yam extract, 3-8 parts of Poria cocos extract, 1-3 parts of cinnamon extract, 3-8 parts of Alpinia oxyphylla extract and 1-3 parts of ginseng extract;

[0013] Preferably, in parts by weight, the Chinese medicine composition comprises 15 parts of Polygonatum odoratum extract, 7.5 parts of yam extract, 5 parts of Poria cocos extract, 1.5 parts of cinnamon extract, 5 parts of Alpinia oxyphylla extract and 1.5 parts of ginseng extract.

[0014] As a preferred embodiment, the extract is a decoction extract.

[0015] As a preferred embodiment, the dosage form of the Chinese medicine composition is an oral dosage form, preferably granules, oral liquid, tablets, syrup or paste.

[0016] In certain specific embodiments, the dosage form of the Chinese medicine composition is a granule, and the granule further comprises dextrin and a sweetener; the granule is prepared by wet granulation, and the wetting agent of the wet granulation is an ethanol solution with a mass fraction of 90 to 95%, preferably an ethanol solution with a mass fraction of 95%;

[0017] Preferably, the sweetener is aspartame.

[0018] In the technical solution of the present invention, the dextrin is used as an excipient.

[0019] In another aspect, the present invention provides a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps:

[0020] Decoct the wine polygonatum, yam, poria, cinnamon bark, alpinia oxyphylla and ginseng in water according to corresponding proportions, combine the medicinal liquids, filter and concentrate.

[0021] As a preferred embodiment, the decoction is performed 1 to 2 times, with 8 to 12 times the amount of water added for the first time and decocted for 1 to 2 hours; and 6 to 8 times the amount of water added for the second time and decocted for 1 to 2 hours.

[0022] As a preferred embodiment, the concentration is reduced pressure concentration;

[0023] Preferably, the concentration is to concentrate to obtain a clear paste with a relative density of 1.15-1.20; in the technical solution of the present invention, the relative density is the relative density measured at 60°C;

[0024] Preferably, the filtration is centrifugal filtration or plate and frame filtration.

[0025] As a preferred embodiment, the yield of the clear paste is in the range of 25-35%.

[0026] In another aspect, the present invention provides use of the above-mentioned Chinese medicine composition in preparing a medicament for treating and / or alleviating mild cognitive impairment.

[0027] The above technical solution has the following advantages or beneficial effects:

[0028] The present invention provides a Chinese medicine composition, which can be obtained by water decoction and extraction, and is mainly used for mild cognitive impairment caused by yang deficiency constitution, and can nourish the kidney and marrow, replenish essence and invigorate qi. The Chinese medicine composition provided by the present invention can be tested for quality standards by content determination using polygonatum polysaccharide and trigonelline in polygonatum as detection indicators.

[0029] The Chinese medicine composition comprises:

[0030] Polygonatum sibiricum and Chinese yam are both monarch drugs. Among them, Polygonatum sibiricum replenishes qi and nourishes yin, benefits the kidney and strengthens the spleen, nourishes the five internal organs, protects health and prolongs life, and is good at nourishing yin and kidney, replenishing essence and benefiting marrow; Chinese yam is sweet and mild, mainly enters the spleen meridian, replenishes spleen yin, strengthens spleen and replenishes deficiency, astringes essence and strengthens kidney;

[0031] Ginseng, Alpinia oxyphylla and Poria cocos are all auxiliary drugs. Among them, ginseng is an important drug for replenishing qi and blood, which can greatly replenish vital energy, restore pulse and consolidate collapse, calm the mind and improve intelligence, replenish the spleen and benefit the lungs, and promote the production of body fluid and nourish blood; Alpinia oxyphylla warms the kidney, consolidates essence and reduces urine, warms the spleen, stops diarrhea and controls saliva, and can be astringent and replenishing. "Bencao Shiyi" records that it "replenishes qi and calms the mind, replenishes deficiency, benefits the three burners, and regulates various qi", emphasizing its warming and replenishing function; Poria cocos lightly penetrates spleen dampness, helps the healthy movement of yam to replenish the acquired foundation;

[0032] Cinnamon is an adjuvant drug that guides fire back to its origin and helps the recovery of qi, which means "less fire brings more vitality".

[0033] The Chinese medicine composition provided by the invention has various medicines used together, which are harmonious and complementary to each other and have specific and great effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 3 is a diagram of the MoCA score interaction (FAS set) of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0035] Figure 2 3 is a diagram of the MoCA score interaction (PPS set) of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0036] Figure 3 It is an interaction diagram (FAS set) of MMSE scores of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0037] Figure 4 It is an interaction diagram (PPS set) of MMSE scores of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0038] Figure 5 It is a memory index score interaction diagram (FAS set) diagram of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0039] Figure 6 It is a memory index score interaction diagram (PPS set) diagram of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0040] Figure 7 3 is a digit span test score interaction diagram (FAS set) of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0041] Figure 8It is a digit span test score interaction diagram (PPS set) diagram of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention.

[0042] Fig. 9 It is a TMT-A score interaction diagram (FAS set) diagram of mild cognitive impairment in an embodiment of the present invention with the baseline period as a covariate.

[0043] Fig.10 It is a TMT-A score interaction diagram (PPS set) diagram of mild cognitive impairment in an embodiment of the present invention with the baseline period as a covariate.

[0044] Fig.11 It is a TMT-B score interaction diagram (FAS set) diagram of mild cognitive impairment in an embodiment of the present invention with the baseline period as a covariate.

[0045] Fig.12 It is a TMT-B score interaction diagram (PPS set) diagram of mild cognitive impairment in an embodiment of the present invention with the baseline period as a covariate.

[0046] Fig.13 It is an ADL score interaction diagram (FAS set) diagram of mild cognitive impairment in an embodiment of the present invention with the baseline period as a covariate.

[0047] Fig.14 It is an ADL score interaction diagram (PPS set) diagram of mild cognitive impairment with the baseline period as a covariate in an embodiment of the present invention. DETAILED DESCRIPTION

[0048] The following embodiments are only some embodiments of the present invention, rather than all embodiments. Therefore, the detailed description in the embodiments of the present invention provided below is not intended to limit the scope of the present invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work belong to the protection scope of the present invention.

[0049] In the present invention, unless otherwise specified, all equipment and raw materials can be purchased from the market or are commonly used in the industry. The methods in the following embodiments are all conventional methods in the art unless otherwise specified.

[0050] Example 1: Clinical evaluation study of intervention technology for mild cognitive impairment

[0051] 1. Research Plan

[0052] (1) Ethical Review

[0053] This project has passed the ethical review of the Ethics Committee of Beijing University of Chinese Medicine, and the ethics review approval number is 2020BZYLL0603.

[0054] (2) Research subjects

[0055] The cases were recruited from outpatient clinics, neighboring communities, and posters in 8 clinical research centers, including Dongzhimen Hospital of Beijing University of Chinese Medicine, Oriental Hospital of Beijing University of Chinese Medicine, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Zaozhuang Hospital of Beijing University of Chinese Medicine, Shenzhen Hospital of Beijing University of Chinese Medicine, Xiamen Hospital of Traditional Chinese Medicine, Sun Simiao Hospital of Beijing University of Chinese Medicine, and China Traditional Chinese Medicine Eye Hospital from January 1, 2021 to December 31, 2021. In this example, the possible population of mild cognitive impairment was screened out by the diagnostic criteria of mild cognitive impairment and the MOCA and MMSE scales. After the patients signed their consent and participated in the study, they completed other scale assessments and those who met the inclusion criteria were enrolled in this study.

[0056] (3) Diagnostic criteria

[0057] Reference MCI diagnostic criteria are based on the Petersen diagnostic criteria, the 2004 MCI International Working Group, the 2006 European Alzheimer's Association (EADC) MCI Working Group, the 2011 MCI diagnostic criteria developed by the National Institute on Aging (NIA) and the Alzheimer's Association (ADA) group, and the 2018 Chinese Dementia and Cognitive Disorders Diagnosis and Treatment Guidelines for MCI:

[0058] ① The patient or an informed person reports a persistent decline in cognitive function; ② Objective evidence (cognitive tests) shows that there is damage to one or more cognitive domains; ③ Daily living ability remains normal, and complex instrumental living ability may be slightly impaired; ④ The diagnosis of dementia has not yet been reached.

[0059] (4) Inclusion and exclusion criteria

[0060] 1) Inclusion criteria

[0061] ① Meet the diagnostic criteria for MCI and be between 50 and 80 years old; ② MoCA score <26, if the years of education are ≤12 years, add 1 point to the score; MMSE score ≥24 points; ③ Daily living ability remains normal (ADL ≤20 points); Geriatric Depression Scale (GDS-15) <8 points.

[0062] Only those who met the above three criteria could be included in the study.

[0063] 2) Exclusion criteria

[0064] ① Those who regularly (at least 3 times a week in the past six months, at least 30 minutes each time) practice traditional sports such as Tai Chi; ② Those with dementia or taking anti-dementia drugs; ③ Those with cognitive impairment caused by acute cerebrovascular disease, Parkinson's dementia, trauma, thyroid disease, anemia, inflammation, etc.; ④ Those with cognitive impairment caused by moderate to severe depression; ⑤ Those with cognitive dysfunction due to poisoning or drugs and other reasons; ⑥ Those who are participating in clinical trials of other professional cognitive interventions and will affect the evaluation of the outcomes of this study; Those who meet any of the above items will be excluded.

[0065] (5) Exit criteria

[0066] ① During the trial, the subject's cognitive decline symptoms continue to worsen, and there is a possibility of dangerous events such as dementia. According to the doctor's judgment, the clinical trial of this case should be stopped. In order to protect the subjects, the subjects should withdraw from the clinical trial and receive other treatments. ② During the trial, the subjects developed certain comorbidities, complications or special physiological changes and were not suitable to continue the trial. ③ During the trial, the subjects had poor compliance and could not be managed according to the management prescription at all. ④ Subjects with adverse events or serious adverse events. ⑤ Subjects who should not be included but have been included should be excluded, including: those who were mistakenly included, misdiagnosed or had no scale assessment records.

[0067] (6) Elimination criteria

[0068] ① Those with extremely poor compliance and who do not follow the intervention treatment as specified throughout the entire process; ② Those who use other related drugs or treatments on their own and regularly use other means of treatment during the intervention period; ③ Subjects who should not be included in the group but have been included should be excluded, including: those who were mistakenly included, misdiagnosed, or have no scale assessment records; ④ Subjects who actively request to withdraw and refuse to provide relevant information required by the project.

[0069] (7) Termination criteria

[0070] If the selected subjects have a condition that is not suitable for continuing the trial during the trial, resulting in the case being unable to complete the trial according to the research plan, the research case is terminated. Generally, termination measures should be taken in the following situations:

[0071] ① If the subject's cognitive function deteriorates sharply or progresses to a level consistent with the diagnosis of dementia during the trial, and it cannot be ruled out that his or her condition is unrelated to the trial, the study case should be considered for termination;

[0072] ② If a subject experiences a serious adverse reaction during the study, the study case should be terminated;

[0073] ③ During the research process, if the subject fails to comply with the clinical trial protocol in terms of protocol execution and record keeping, and the researcher determines that this may affect the authenticity of the research results, the research case should be considered to be terminated;

[0074] ④ Those who withdraw from the trial on their own initiative;

[0075] After the case is terminated, the case record sheet should be retained, and the last test result should be taken as the final result for efficacy and adverse reaction data analysis.

[0076] (8) Sample size calculation

[0077] According to international standards, we strictly conduct clinical evaluation research on comprehensive TCM intervention technology for MCI, and carry out multicenter randomized controlled studies. Sample size calculation: According to the outcome indicators of mild cognitive impairment intervention evaluation, the minimum sample size is calculated (the formula is as follows). At the same time, in order to ensure the sample size, we refer to the sample size requirements of Phase III clinical trials in the "Drug Registration Management Measures". Finally, 500 cases were included and randomly assigned in a ratio of 3:1, with 375 cases in the intervention group and 125 cases in the control group.

[0078] (9) Random setting method

[0079] A computer system is used for dynamic randomization. The subjects fill in relevant information in the medical evaluation management system. After the researchers determine that they meet the inclusion criteria or do not meet the exclusion criteria, they click on the system to agree to join the group, and the system automatically assigns the patients to groups.

[0080] (10) Active and Passive Intervention Schemes

[0081] 1) Basic treatment: health education

[0082] Educational content: Distribute the self-made "Mild Cognitive Impairment Health Education Manual", and explain the concept, incidence, causes, clinical manifestations, diagnosis, risk factors, treatment measures, preventive measures, etc. of mild cognitive impairment based on the contents of the manual.

[0083] Education forms: ① One-on-one education is carried out when distributing health education manuals, and the education time is 10-20 minutes; ② Regular education is carried out on WeChat public accounts, APPs and WeChat groups:

[0084] Education population: All participants (control group and intervention group)

[0085] 2) Drug intervention: Zengzhiyin (the Chinese medicine composition of the present invention)

[0086] Zengzhi Drink has the effects of nourishing the kidney and yang, increasing intelligence and strengthening the brain. Each bag of Zengzhi Drink is made of 0.75g of ginseng, 2.5g of yiqiren, 0.75g of cinnamon, 7.5g of wine polygonatum, 3.75g of yam, and 2.5g of poria. The specific preparation method is as follows:

[0087] (1) Decoction and extract each component twice according to the corresponding mass, add 10 times the amount of water for the first time and decoct for 1.5 hours, add 8 times the amount of water for the second time and decoct for 1 hour, and then combine the filtrates; centrifuge the filtrate and filter it through a 300-mesh polyester cloth centrifugal filter or plate and frame filter press, and decompress and concentrate the filtrate to a clear paste with a relative density of 1.15-1.20 (60°C);

[0088] (2) Add dextrin as an excipient in a mass ratio of 1:1 to 1:1.5 to the above-mentioned clear paste, use aspartame as a sweetener, and use 90%-95% ethanol solution as a wetting agent to perform wet granulation to obtain Xiaokeyin granules.

[0089] Among them, ginseng is an important medicine for replenishing qi and blood, which can greatly replenish vital energy, restore pulse and strengthen deficiency, calm the mind and improve intelligence, nourish the spleen and lungs, and promote the production of body fluid and blood; Yiqiren warms the kidney, consolidates essence and reduces urine, warms the spleen, stops diarrhea and controls saliva, and can be astringent and replenishing. "Bencao Shiyi" records that it "replenishes qi and calms the mind, replenishes deficiency, benefits the three burners, and regulates all qi", emphasizing its warming and replenishing function; Huangjing replenishes qi and nourishes yin, replenishes the kidney and strengthens the spleen, nourishes the five internal organs, and prolongs life. It is good at nourishing yin and kidney, replenishing essence and benefiting marrow; Chinese yam is sweet and mild, mainly enters the spleen meridian, replenishes spleen yin, strengthens the spleen and replenishes deficiency, astringes essence and consolidates the kidney. Poria cocos is light in penetrating spleen dampness, and helps Chinese yam to move healthily to nourish the acquired foundation. Cinnamon bark can lead fire back to the origin, help the recovery of qi transformation, and take the meaning of "less fire brings vitality". All the medicines are used together to replenish the kidney and increase intelligence, and they are harmonious and complementary, with special effects and great power.

[0090] Control group: None

[0091] Intervention group: Zhizhi Drink, 1 bag / time, 2 times a day

[0092] Distribution method: Monthly distribution, and it will only be distributed when the usage rate is greater than 60%.

[0093] (11) Efficacy evaluation criteria

[0094] 1) Main efficacy indicators

[0095] MoCA scale score: The overall cognitive function of this study was assessed using the MoCA scale, which is a tool specifically used for MCI screening and has high sensitivity. The scale includes 8 aspects: visual-spatial and executive ability (0-5 points), naming (0-3 points), memory (not scored), attention (0-6 points), language (0-3 points), abstraction (0-2 points), delayed recall (0-5 points), and orientation (0-6 points). The total score is 30 points. The higher the score obtained, the better the cognitive function. MoCA memory index (MoCA-MIS) = delayed recall correct number __ × 3 + classification prompt correct number __ × 2 + multiple choice prompt correct number __ × 1.

[0096] 2) Secondary clinical efficacy indicators

[0097] MMSE (mini-state examination), traditional Chinese medicine body mass scale, MoCA memory index, daily living ability score (ADL), digit span test, line connection test AB, Boston naming test, clock drawing test, etc.

[0098] (12) Safety evaluation indicators

[0099] Routine blood test, routine urine test, biochemistry test, electrocardiogram, etc.

[0100] (13) Clinical research quality control plan

[0101] The study was registered with the China Clinical Trial Registration Platform, and a Clinical Event Verification Committee (CEC) and Data Safety Monitoring Committee (DSMB) independent of the study were established. Clinical monitors were hired to ensure that the study was conducted strictly in accordance with the requirements of the Good Clinical Practice (GCP). Standardized operating procedures (SOPs) were formulated during the research process, and researchers from each center were uniformly trained to ensure homogeneity among different researchers.

[0102] (14) Data Statistical Methods

[0103] This study was an intention-to-treat analysis, and the full analysis set (FAS) and per-protocol set (PPS) were used for efficacy statistics. The lost data in the full analysis set were filled with the last data before the lost data.

[0104] The medical evaluation management system can export the collected patient data, including basic information and scale data. SPSS20.0 statistical software was used for descriptive statistics, chi-square test, rank sum test, and generalized estimating equation analysis. All statistical analyses were considered statistically significant when P < 0.05.

[0105] Quantitative data: Data that conform to the basic normal distribution are described by mean ± standard deviation, and data that do not conform to the normal distribution are expressed by IQR. The scores of each scale are repeated measurement data, and generalized estimating equations are used for analysis. The total score of each scale is analyzed with the baseline data at the time of enrollment as the covariate, and the measurement data at other times as the dependent variable. The generalized estimating equation uses the unstructured covariance working matrix.

[0106] Qualitative data: expressed as "percentage (%)", and contingency table data were tested using Fisher's exact test.

[0107] 2. Research Results

[0108] (1) Baseline data

[0109] The baseline data of the two groups were compared separately. There were no significant statistical differences in gender, age, education level, drinking habits, smoking habits, exercise habits, social activities, marital status, whether living alone, and underlying diseases (hypertension, diabetes, coronary heart disease, hyperlipidemia) between the two groups (P>0.05). The baseline general data were comparable.

[0110] The two groups were compared in each index before treatment. The overall cognitive function MoCA score showed statistical difference (P=0.028), while the other baseline scales showed no statistical difference (see Table 130).

[0111] Table 130 Baseline data of FAS group of mild cognitive impairment

[0112]

[0113]

[0114] (2) Comparison of shedding rate

[0115] A total of 49 people dropped out of this study, including 11 in the control group with a dropout rate of (8.52%); 38 in the intervention group with a dropout rate of (10.13%). There was no significant difference in the dropout rate between the two groups (P=0.157) (see Table 131).

[0116] Table 131 Comparison of dropout cases between the two groups of mild cognitive impairment

[0117] Group Total number of people Number of people who dropped out percentage P Control group 129 11 14.52％ 0.157 Intervention Group 375 38 17.24％

[0118] (3) Evaluation of main efficacy indicators

[0119] The MoCA scale reflects the overall cognitive function of MCI. The higher the score, the better the overall cognitive function. In this study, the MoCA scores of each group of subjects were measured before intervention, 12 weeks of intervention, and 24 weeks of intervention, and the FAS set and PPS set statistical analysis of MoCA were performed. Inter-group analysis showed that there were statistical differences in MoCA scores between the intervention group and the control group at weeks 12 and 24, and the statistical results of the FAS set and PPS set were consistent. The specific analysis results are described as follows:

[0120] 1) Analysis of FAS set of MoCA scores in two groups

[0121] After filling the missing FAS set with the expectation maximization algorithm (EM method) in SPSS, the generalized estimating equation analysis of the correlation matrix model with equal correlation structure was selected. Since the baseline MoCA scores of the two groups were statistically different, the baseline MoCA scores were used as covariates for statistical analysis using generalized estimating equations. The results showed that the intervention effect, time effect, and intervention-time interaction effect were all statistically significant. The results of the intervention effect analysis showed that the mean MoCA score of the intervention group was statistically different from that of the control group at 24 weeks of intervention (P < 0.001) when the main effect was corrected for the baseline MoCA score. The time effect analysis showed that the mean MoCA score of the intervention group was statistically different from that of the control group at 12 and 24 weeks (P < 0.001).

[0122] In general, the MoCA scores of the intervention group at 12 and 24 weeks of intervention were significantly different from those at baseline (P < 0.001); the MoCA scores of the control group at 12 and 24 weeks of intervention were significantly different from those at baseline (P < 0.001).

[0123] At week 12, there was a statistically significant difference in MoCA scores between the two groups (LS mean -0.796, 95% CI [-1.326, -0.266], P = 0.003), with the intervention group being higher than the control group; at week 24, there was a statistically significant difference in MoCA scores between the two groups (LS mean -1.545, 95% CI [-2.089, -1.001], P < 0.001), with the intervention group being higher than the control group (see Table 132, Table 133, Figure 1 ).

[0124] Table 132 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0125] Results of the FAS set main effect model Results of the PPS set main effect model Intervention Group <![CDATA[<0.001 * ]]> <![CDATA[<0.001 * ]]> time <![CDATA[<0.001 * ]]> <![CDATA[<0.001 * ]]> Baseline MoCA score <![CDATA[<0.001 * ]]> <![CDATA[<0.001 * ]]> <![CDATA[Intervention grouping * Time]]> <![CDATA[0.001 * ]]> <![CDATA[<0.001 * ]]>

[0126] Table 133 Comparison of MoCA scores among groups in mild cognitive impairment (FAS set)

[0127]

[0128] 2) PPS set analysis of MoCA scores in two groups

[0129] PPS set analysis showed that after generalized estimating equation analysis (see Table 6 for details), when the main effect was corrected for the baseline value, the MoCA scores of the intervention group were statistically different from those of the control group at 24 weeks of intervention (P < 0.001), the MoCA scores at different time points (12 and 24 weeks) were statistically different (P < 0.001), and the interaction effect was statistically significant (P < 0.001).

[0130] In general (see Table 8 for details), the MoCA scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001); the MoCA scores of the control group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001).

[0131] There was a statistically significant difference in MoCA scores between the intervention group and the control group at week 12 (LS mean -0.721, 95% CI [-1.257, -0.185], P = 0.008), and the intervention group was higher than the control group; there was a statistically significant difference in MoCA scores between the two groups at week 24 (LS mean -1.553, 95% CI [-2.108, -0.997], P < 0.001), and the intervention group was higher than the control group (see Table 134, Figure 2 ).

[0132] Table 134 Comparison of MoCA scores among groups in mild cognitive impairment (PPS set)

[0133]

[0134] (3) Evaluation of secondary efficacy indicators

[0135] 1) MMSE scores of the two groups

[0136] The MMSE scale reflects the overall cognitive function of MCI, and the higher the score, the better the overall cognitive function. This study included MCI subjects with MMSE scores ≥ 24 points. The MMSE scores of each group of subjects were measured before intervention, 12 weeks of intervention, and 24 weeks of intervention, and the two groups were statistically analyzed by FAS and PPS sets. There was no statistical difference in MMSE scores between the intervention group and the control group at week 12, and the statistical results of the FAS and PPS sets were consistent; the statistical results of the FAS and PPS sets of the MMSE scores of the two groups at week 24 were inconsistent, and the statistical results of the FAS set were the main ones, so the MMSE scores of the two groups at week 24 were statistically different. The specific analysis results are described as follows:

[0137] ① Analysis of MMSE scores and FAS set in the two groups

[0138] The results of FAS set analysis showed that after generalized estimating equation analysis, when the main effect was corrected for the baseline value, the mean MMSE score of the intervention group was statistically different from that of the control group at 24 weeks of intervention (P=0.002), there was no statistical difference in the MMSE scores at different time points (12 and 24 weeks) (P=0.477), and there was no statistical difference in the interaction effect (P=0.734).

[0139] In general (see Table 16), there were statistically significant differences in the MMSE scores of the intervention group at 12 and 24 weeks compared with the baseline scores (P < 0.001); there was no statistically significant difference in the MMSE scores of the control group at 12 and 24 weeks compared with the baseline scores (P = 0.847).

[0140] There was a statistically significant difference in MMSE scores between the intervention group and the control group at week 12 (LS mean -0.666, 95% CI [-1.294, -0.037], P = 0.038), and the score in the intervention group was higher than that in the control group; there was a statistically significant difference in MMSE scores between the two groups at week 24 (LS mean -0.548, 95% CI [-1.054, -0.042], P = 0.034), and the score in the intervention group was higher than that in the control group (see Table 135, Table 136, Figure 3 ).

[0141] Table 135 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0142]

[0143] Table 136 Comparison of MMSE scores among groups in mild cognitive impairment (FAS set)

[0144]

[0145] ② PPS set analysis of MMSE scores in the two groups

[0146] The results of PPS set analysis showed that after generalized estimating equation analysis, when the main effect was corrected for the baseline value, the mean MMSE score of the intervention group was statistically different from that of the control group at 24 weeks of intervention (P=0.001), there was no statistical difference in the MMSE scores at different time points (12 and 24 weeks) (P=0.452), and there was no statistical difference in the interaction effect (P=0.764).

[0147] In general (see Table 17), there were statistically significant differences in the MMSE scores of the intervention group at 12 and 24 weeks compared with the baseline scores (P < 0.001); there was no statistically significant difference in the MMSE scores of the control group at 12 and 24 weeks compared with the baseline scores (P = 0.776).

[0148] There was a statistically significant difference in MMSE scores between the intervention group and the control group at week 12 (LS mean -0.606, 95% CI [-1.126, -0.086], P = 0.022), and the score in the intervention group was higher than that in the control group; there was no statistically significant difference in MMSE scores between the two groups at week 24 (LS mean -0.035, 95% CI [-0.431, 0.361], P = 0.862) (see Table 137, Figure 4 ).

[0149] Table 137 Mild cognitive impairment Table 136 Comparison of MMSE scores between groups (PPS set)

[0150]

[0151]

[0152] 2) Memory index scores of the two groups

[0153] The memory index score reflects the memory function of MCI, and the higher the score, the better the memory function. The memory index score of each group of subjects was assessed before intervention, 12 weeks of intervention, and 24 weeks of intervention, and the two groups were statistically analyzed by FAS set and PPS set. Inter-group analysis showed that there was no statistical difference in the memory index score between the intervention group and the control group at week 12, and the statistical results of the FAS set and PPS set were consistent; the statistical results of the FAS set and PPS set of the memory index score of the two groups at week 24 were inconsistent, and the statistical results of the FAS set were the main ones, so the memory index score of the two groups at week 24 had statistical differences. The specific analysis results are described as follows:

[0154] ① Analysis of FAS set of memory index scores in the two groups

[0155] The results of FAS set analysis showed that after generalized estimating equation analysis, when the main effect was corrected for the baseline value, the memory index score of the intervention group was statistically different from that of the control group at 24 weeks of intervention (P=0.002), and there were statistical differences in the memory index scores at different time points (12 and 24 weeks) (P<0.001), and the interaction effect was statistically significant (P<0.001).

[0156] In general (see Table 19), the memory index scores of the intervention group at 12 and 24 weeks were statistically different from those at the baseline (P < 0.001); the memory index scores of the control group at 12 and 24 weeks were statistically different from those at the baseline (P < 0.001).

[0157] There was no statistical difference in the memory index scores between the intervention group and the control group at week 12 (LS mean -0.57, 95% CI [-1.345, 0.205], P = 0.149); there was no statistical difference in the memory index scores between the two groups at week 24 (LS mean -0.43, 95% CI [-0.915, 0.054], P = 0.082) (see Table 138, Table 139, Figure 5 ).

[0158] Table 138 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0159] Main effects model with interaction terms (FAS set) Main effects model with interaction terms (PPS set) Intervention Group 0.002 0.003 time <![CDATA[<0.001 * ]]> 0.227 Baseline value 0.009 <![CDATA[<0.001 * ]]> <![CDATA[Experimental grouping * Time]]> <![CDATA[<0.001 * ]]> <![CDATA[<0.001 * ]]>

[0160] Table 139 Comparison of mild cognitive impairment memory index scores between groups (FAS set)

[0161]

[0162] ② PPS set analysis of memory index scores in the two groups

[0163] The results of PPS set analysis showed that after generalized estimating equation analysis, when the main effect was corrected for the baseline value, the memory index score of the intervention group was statistically different from that of the control group at 24 weeks of intervention (P=0.003), while there was no statistical difference in the memory index scores at different time points (12 and 24 weeks) (P=0.227), and the interaction effect was statistically significant (P<0.001).

[0164] In general, the memory index scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001); the memory index scores of the control group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001).

[0165] There was no statistical difference in the memory index scores between the intervention group and the control group at week 12 (LS mean -0.621, 95% CI [-1.375, 0.134], P = 0.107); there was a statistical difference in the memory index scores between the two groups at week 24 (LS mean -0.534, 95% CI [-1.012, -0.057], P = 0.028) (see Table 140, Figure 6 ).

[0166] Table 140 Comparison of mild cognitive impairment memory index scores between groups (PPS set)

[0167]

[0168] 3) Two sets of digit span tests

[0169] The digit span test reflects the executive function of MCI, and the higher the score, the better the executive function. The subjects in each group were given a digit span test before the intervention, at 12 weeks of intervention, and at 24 weeks of intervention, and the two groups were statistically analyzed by FAS and PPS sets. The inter-group analysis results showed that there was a statistical difference in the digit span test scores between the intervention group and the control group at week 12, and the statistical results of the FAS and PPS sets were consistent; the statistical results of the FAS and PPS sets of the digit span test scores of the two groups at week 24 were inconsistent, with the FAS set statistical results being the main ones, so there was a statistical difference in the digit span test scores of the two groups at week 24. The specific analysis results are described as follows:

[0170] ①Digit Span Test FAS Set Analysis

[0171] The results of the FAS set showed that after generalized estimating equation analysis, when the main effect was corrected for the baseline value, there was no statistical difference in the digit span test scores between the intervention group and the control group after the intervention (P=0.051), while there was a statistical difference in the digit span test scores at different time points (12 and 24 weeks) (P=0.020), and there was no statistical difference in the interaction effect (P=0.604).

[0172] In general, the digit span test scores of the intervention group at 12 and 24 weeks were statistically different from those at baseline (P=0.045); there was no statistically significant difference in the digit span test scores of the control group at 12 and 24 weeks compared with those at baseline (P=0.325).

[0173] There was a statistically significant difference in the digit span test scores between the intervention group and the control group at week 12 (LS mean -0.897, 95% CI [-1.488, -0.307], P = 0.003), and the score in the intervention group was higher than that in the control group; there was a statistically significant difference in the digit span test scores at week 24 (LS mean -0.775, 95% CI [-1.385, -0.165], P = 0.013), and the score in the intervention group was higher than that in the control group (see Table 141, Table 142, Figure 7 ).

[0174] Table 141 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0175]

[0176] Table 142 Comparison of Digit Span Test Scores among Mild Cognitive Impairment Groups (FAS Set)

[0177]

[0178] ② PPS set analysis of two groups of digit span tests

[0179] The results of the PPS set showed that after the generalized estimating equation analysis, the intervention group had no statistically significant difference in the digit span test score after the intervention compared with the control group when the baseline value was corrected for the main effect (P=0.051). The digit span test scores at different time points (12 and 24 weeks) were statistically different from the baseline scores (P=0.061), and there was no statistically significant difference in the interaction effect (P=0.952).

[0180] In general, the digit span test scores of the intervention group at 12 and 24 weeks were statistically different from those at baseline (P=0.045); there was no statistically significant difference in the digit span test scores of the control group at 12 and 24 weeks compared with those at baseline (P=0.325).

[0181] There was a statistically significant difference in the digit span test scores between the intervention group and the control group at week 12 (LS mean -0.733, 95% CI [-1.278, -0.189], P = 0.008), and the score of the intervention group was higher than that of the control group; there was no statistically significant difference in the digit span test scores between the 24th week and the baseline period (LS mean -0.747, 95% CI [-1.366, -0.128], P = 0.018), and the score of the intervention group was higher than that of the control group (see Table 143, Figure 8 ).

[0182] Table 143 Comparison of scores of digit span test in patients with mild cognitive impairment between groups (PPS set)

[0183]

[0184] 4) Two groups of connection test AB scoring

[0185] The AB test reflects the executive function of MCI. The higher the score, the better the executive function. This study conducted AB test on each group of subjects before intervention, 12 weeks of intervention, and 24 weeks of intervention, and the AB test scores were statistically analyzed by FAS and PPS sets. Inter-group analysis showed that there was no statistical difference in MoCA scores between the intervention group and the control group at weeks 12 and 24, and the statistical results of FAS and PPS sets were consistent. The specific analysis results are described as follows:

[0186] ① Analysis of TMT-A scores in the two groups by FAS set

[0187] The results of the FAS set showed that after generalized estimating equation analysis, when the baseline value was corrected for the main effect, there was no statistical difference in TMT-A scores between the intervention group and the control group at 24 weeks of intervention (P=0.242), and there was no statistical difference in TMT-A scores at different time points (12 and 24 weeks) (P=0.737), and there was no statistical difference in the interaction effect (P=0.317).

[0188] In general (see Table 25), there were statistically significant differences in the digit span test scores of the intervention group at 12 and 24 weeks compared with the baseline scores (P=0.011); there were statistically significant differences in the digit span test scores of the control group at 12 and 24 weeks compared with the baseline scores (P=0.025).

[0189] There was no statistical difference in the digit span test scores between the intervention group and the control group at week 12 (LS mean -4.811, 95% CI [-11.509, 1.886], P = 0.159); there was no statistical difference in the TMT-A scores between the two groups at week 24 (LS mean -1.929, 95% CI [-8.548, 4.69], P = 0.568) (see Table 144, Table 145, Fig. 9 ).

[0190] Table 144 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0191]

[0192] Table 145 Comparison of TMT-A scores among groups in patients with mild cognitive impairment (FAS set)

[0193]

[0194] ② PPS set analysis of TMT-A scores in the two groups

[0195] The results of the PPS set showed that after the generalized estimating equation analysis, the main effect was corrected for the baseline value, and there was no statistical difference in TMT-A scores between the intervention group and the control group after the intervention (P=0.229). There was no statistical difference in TMT-A scores at different time points (12 and 24 weeks) (P=0.73), and there was no statistical difference in the interaction effect (P=0.443).

[0196] In general, the TMT-A scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P=0.007); the TMT-A scores of the control group at 12 and 24 weeks were significantly different from those at baseline (P=0.037).

[0197] There was no statistical difference in TMT-A scores between the intervention group and the control group at week 12 (LS mean 0.523, 95% CI [-1.076, 0.03], P = 0.064); there was no statistical difference in TMT-A scores between the two groups at week 24 (LS mean 0.382, 95% CI [-0.917, 0.154], P = 0.162) (see Table 146, Fig.10 ).

[0198] Table 146 Comparison of TMT-A scores among groups in patients with mild cognitive impairment (PPS set)

[0199]

[0200]

[0201] ③FAS analysis of TMT-B scores in the two groups

[0202] The results of the FAS set showed that after generalized estimating equation analysis, the main effect was corrected for the baseline value, and there was no statistical difference in TMT-B scores between the intervention group and the control group after intervention (P=0.229). There was no statistical difference in TMT-B scores at different time points (12 and 24 weeks) (P=0.73), and there was no statistical difference in the interaction effect (P=0.443).

[0203] In general, the TMT-B scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001); the TMT-B scores of the control group at 12 and 24 weeks were significantly different from those at baseline (P = 0.035).

[0204] There was no statistical difference in TMT-B scores between the intervention group and the control group at week 12 (LS mean 0.523, 95% CI [-1.076, 0.03], P = 0.064); there was no statistical difference in TMT-B scores between the two groups at week 24 (LS mean 0.382, 95% CI [-0.917, 0.154], P = 0.162) (see Table 147, Table 148, Fig.11 ).

[0205] Table 147 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0206]

[0207] Table 148 Comparison of TMT-B scores among groups in patients with mild cognitive impairment (FAS set)

[0208]

[0209] ④ PPS set analysis of TMT-B scores in the two groups

[0210] The results of PPS set analysis showed that after generalized estimating equation analysis, the main effect showed no statistical difference in TMT-B scores between the intervention group and the control group after 24 weeks of intervention (P=0.641), and there were statistical differences in TMT-B scores at different time points (12 and 24 weeks) (P<0.001). * ), and the interaction effect had no statistically significant difference (P=0.561).

[0211] In general, the TMT-B scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P < 0.001); the TMT-B scores of the control group at 12 and 24 weeks were significantly different from those at baseline (P = 0.002).

[0212] There was no statistical difference in TMT-B scores between the intervention group and the control group at week 12 (LS mean 0.178, 95% CI [-11.257, 12.009], P = 0.949); there was no statistical difference in TMT-B scores between the intervention group and the control group at week 24 (LS mean 3.122, 95% CI [-8.759, 15.003], P = 0.607) (see Table 149, Fig.12 ).

[0213] Table 149 Comparison of TMT-B scores among groups in patients with mild cognitive impairment (PPS set)

[0214]

[0215] 5) Scores of activities of daily living (ADL) in the two groups

[0216] This study evaluated the ADL scores of the subjects in each group before intervention, 12 weeks of intervention, and 24 weeks of intervention, and analyzed the ADL scores by FAS and PPS sets. Inter-group analysis showed that there was no statistical difference in ADL scores between the intervention group and the control group at weeks 12 and 24, and the statistical results of the FAS and PPS sets were consistent. The specific analysis results are described as follows:

[0217] ① Analysis of FAS set of ADL scores in the two groups

[0218] The generalized estimating equation analysis showed that after adjusting the baseline value, the ADL scores of the intervention group and the control group had no statistical difference after 24 weeks of intervention (P = 0.938), and there was no statistical difference between the ADL scores at different time points (12 and 24 weeks) and the baseline scores (P = 0.979), and there was no statistical difference in the interaction effect (P = 0.544) (see Fig.13 ).

[0219] In general, the ADL scores of the intervention group at 12 and 24 weeks were significantly different from those at baseline (P=0.032); while the ADL scores of the control group at 12 and 24 weeks were not significantly different from those at baseline (P=0.203).

[0220] There was no statistical difference in ADL scores between the intervention group and the control group at week 12 (LS mean -0.017, 95% CI [-0.203, 0.169], P = 0.858); there was no statistical difference in ADL scores between the two groups at week 24 (LS mean 0.025, 95% CI [-0.158, 0.209], P = 0.786) (see Table 150, Table 151, Fig.13 ).

[0221] Table 150 Main effect model test of mild cognitive impairment (FAS set and PPS set)

[0222]

[0223] Table 151 Comparison of ADL scores among groups in patients with mild cognitive impairment (FAS set)

[0224]

[0225] ② PPS analysis of ADL scores in the two groups

[0226] Generalized estimating equation analysis showed that after adjusting the baseline value, there was no statistical difference in ADL scores between the intervention group and the control group after 24 weeks of intervention (P=0.807), and there was no statistical difference in ADL scores at different time points (12 and 24 weeks) (P=0.769), and there was no statistical difference in the interaction effect (P=0.459).

[0227] In general, there were statistically significant differences in the ADL scores between the intervention group at 12 and 24 weeks and the baseline scores (P=0.028); there were no statistically significant differences in the ADL scores between the control group at 12 and 24 weeks and the baseline scores (P=0.297).

[0228] There was no statistical difference in ADL scores between the intervention group and the control group at week 12 (LS mean -0.013, 95% CI [-0.199, 0.172], P = 0.858); there was no statistical difference in ADL scores between the two groups at week 24 (LS mean 0.036, 95% CI [-0.149, 0.22], P = 0.707) (see Table 152, Fig.14 ).

[0229] Table 152 Comparison of ADL scores among groups in patients with mild cognitive impairment (PPS set)

[0230]

[0231]

[0232] (4) Safety indicators

[0233] According to the analysis of safety indicators, one patient developed a rash at the beginning of medication, and the symptoms improved after stopping the medication, and no rash appeared after continuing to take the medication; one patient had elevated blood sugar after taking the medication, and blood sugar decreased after stopping the medication; one patient developed hot flashes after taking the medication. No other obvious abnormalities were found in renal function, urine and stool routine, and electrocardiogram. No related sports injuries occurred in the intervention group. This shows that the comprehensive Chinese medicine intervention program has good safety.

[0234] 3. Analysis and Discussion

[0235] (1) Main efficacy indicators

[0236] The FAS set analysis showed that both the intervention group and the control group could improve MoCA scores, indicating that Tai Chi combined with Zengzhiyin group and health education could improve MCI cognitive function. The intergroup analysis of MoCA scores of the two groups at different time points (12 weeks and 24 weeks) showed that there were statistical differences in MoCA scores between the two groups at weeks 12 and 24, indicating that on the basis of health education, Zengzhiyin had a better overall efficacy in improving MoCA scores than the control group, and the longer the intervention time, the better the efficacy.

[0237] (2) Exploratory analysis

[0238] According to age, the MCI subjects were divided into two groups: those aged 50-60 years and those aged over 60 years. Through the analysis of the MCI population over 60 years old, it was found that compared with the control group, Tai Chi combined with Zengzhiyin can effectively improve the MoCA score, and the difference is statistically significant. Inter-group analysis at different time points found that there was no statistical difference in the MoCA scores of the two groups at week 12, while there was a statistical difference in the MoCA scores of the two groups at week 24. This suggests that for MCI people over 60 years old, Tai Chi combined with Zengzhiyin is better than the control group in improving MoCA scores, but the advantage is effective after 24 weeks of intervention.

[0239] In the MCI population aged 50-60 years old, compared with the control group, Tai Chi combined with Zengzhiyin can effectively improve the MoCA score, and the difference is statistically significant, and the differences at different time points of week 12 and week 24 are statistically significant. This shows that for the MCI population aged 50-60 years old, Tai Chi combined with Zengzhiyin is better than the control group, and the advantage is obvious within 12 weeks of intervention.

[0240] Therefore, for MCI people aged 50 to under 60 years old, the comprehensive Chinese medicine program can show its advantages within 12 weeks, while for MCI people aged over 60 years old, it will take at least 24 weeks to show its advantages.

[0241] (3) Secondary efficacy indicators

[0242] ①MMSE score

[0243] The results of FAS set analysis showed that the intervention group could improve the MMSE score, while the control group had no effect on MMSE. The inter-group results showed that there were statistical differences in the MMSE scores between the intervention group and the intervention group at weeks 12 and 24, indicating that Tai Chi combined with Zengzhiyin was superior to the control group in improving the MMSE score, and the efficacy of the intervention group gradually increased with the intervention time.

[0244] ②Memory index score

[0245] The results of FAS set analysis showed that both the intervention group and the control group could improve the MoCA memory index score. The inter-group results showed that there was no statistical difference in the MoCA memory index score between the intervention group and the control group at week 12 and week 24, indicating that the intervention group had a similar effect as the control group in improving the MoCA memory index score.

[0246] ③Digit span test

[0247] The results of FAS set analysis showed that the intervention group could improve the digit span test score, while the control group had no effect on the digit span test score. The inter-group analysis results showed that there were statistical differences in the digit span test scores between the intervention group and the intervention group at week 12 and week 24, indicating that Tai Chi combined with Zengzhiyin was superior to the control group in improving the digit span test score, and the efficacy of the intervention group gradually increased with the intervention time.

[0248] ④Connection test AB test

[0249] The results of FAS set analysis showed that both the intervention group and the control group could improve the TMT-A and TMT-B test scores. Inter-group analysis showed that there was no statistical difference in the TMT-A and TMT-B scores between the intervention group and the control group at week 12 and week 24, indicating that the intervention group had the same efficacy as the control group in terms of the AB scores of the line connection test.

[0250] ⑤ADL score

[0251] The results of FAS set analysis showed that the intervention group could improve the ADL score, while the control group had no effect on the ADL score. The inter-group results showed that there was no statistical difference in the ADL scores between the intervention group and the control group at week 12 and week 24, indicating that the intervention group had the same efficacy as the control group in terms of ADL scores.

[0252] ⑥Boston naming test

[0253] The results of FAS set analysis showed that both the intervention group and the control group could improve the Boston naming test scores. The inter-group results showed that there was no statistical difference in the Boston naming test scores between the intervention group and the control group at week 12 and week 24, indicating that the intervention group had a similar effect as the control group in improving the Boston naming test scores.

[0254] ⑦ Clock drawing test

[0255] The results of FAS set analysis showed that both the intervention group and the control group could improve the clock drawing test scores. The inter-group results showed that there was no statistical difference in the clock drawing test scores between the intervention group and the control group at week 12, but there was a statistical difference at week 24, indicating that Tai Chi combined with Zengzhi Drink was superior to the control group in improving the clock drawing test scores.

[0256] ⑧ TCM constitution score

[0257] The results of FAS set analysis showed that the control group could reduce the scores of qi deficiency, phlegm-dampness, blood stasis and qi stagnation in the subjects; the intervention group could improve the score of peaceful constitution and reduce the scores of other biased constitutions except special constitution. However, there was no significant difference in the improvement of the scores of 9 TCM constitutions before and after the intervention between the intervention group and the control group.

[0258] (4) Effectiveness analysis

[0259] From the analysis results of the main efficacy indicator MoCA score, compared with the control group, the comprehensive TCM intervention program (Tai Chi + Zengzhi Drink + health education) can significantly improve the MoCA score and improve the cognitive function of MCI; and in terms of time benefit, the longer the intervention time, the more obvious the effect. The comparison before and after the intervention found that health education (control group) can improve MoCA, indicating that health education can enhance the prevention and treatment awareness of MCI people, promote their adjustment of bad habits, and help cognitive function.

[0260] Exploratory analysis found that in MCI population over 60 years old, the comprehensive Chinese medicine program improved MoCA scores better than the control group, but this advantage was not apparent until at least 12 weeks of intervention. In MCI population aged 50-60 years old, Tai Chi combined with Zengzhi Drink was better than the control group, and this advantage took effect in a short time.

[0261] Secondary efficacy indicators showed that the comprehensive TCM intervention program could effectively improve the MMSE score, the digit span test score, and the clock drawing test score, and was superior to the control group. Although the two groups had comparable efficacy in improving TCM constitution, it was found that the intervention group could improve the scores of the other eight constitutions except for the special constitution before and after the intervention, suggesting that the comprehensive TCM intervention program could adjust multiple physical states of MCI. Comparison before and after the intervention showed that health education (control group) could improve MMSE, MoCA memory index scores, TMTA-B scores, Boston naming test scores and some physical states, indicating that health education can enhance the prevention and treatment awareness of MCI people and promote them to adjust bad habits, which is helpful to improve multiple cognitive domains and physical states.

[0262] From the perspective of safety analysis, Zengzhi Tai Chi has good safety and causes less knee joint damage than traditional 24-posture Tai Chi. Although Zengzhi Drink has some adverse reactions such as dryness, rash, and increased blood sugar, its overall safety is good.

[0263] In summary, the TCM intervention program based on the combination of active and passive methods can effectively improve MCI cognitive function and related cognitive domains, regulate various physical conditions of MCI people in addition to their special constitution, and has good safety, which is worthy of large-scale clinical promotion.

[0264] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating and / or alleviating mild cognitive impairment, characterized in that: In parts by weight, the Chinese medicine composition comprises 5-20 parts of Polygonatum odoratum, 2-10 parts of yam, 2-10 parts of Poria cocos, 1-5 parts of cinnamon bark, 2-10 parts of Alpinia oxyphylla and 1-5 parts of ginseng.

2. The Chinese medicine composition according to claim 1, characterized in that: In parts by weight, the Chinese medicine composition comprises 10-20 parts of Polygonatum odoratum, 5-10 parts of Chinese yam, 3-8 parts of Poria cocos, 1-3 parts of cinnamon bark, 3-8 parts of Alpinia oxyphylla and 1-3 parts of ginseng; Preferably, in parts by weight, the Chinese medicine composition comprises 15 parts of Polygonatum odoratum, 7.5 parts of yam, 5 parts of Poria cocos, 1.5 parts of cinnamon bark, 5 parts of Alpinia oxyphylla and 1.5 parts of ginseng.

3. A Chinese medicine composition for treating and / or alleviating mild cognitive impairment, characterized in that: In parts by weight, the Chinese medicine composition comprises 5-20 parts of Polygonatum odoratum extract, 2-10 parts of yam extract, 2-10 parts of Poria cocos extract, 1-5 parts of cinnamon extract, 2-10 parts of Alpinia oxyphylla extract and 1-5 parts of ginseng extract.

4. The Chinese medicine composition according to claim 3, characterized in that: In parts by weight, the Chinese medicine composition comprises 10-20 parts of Polygonatum sibiricum extract, 5-10 parts of yam extract, 3-8 parts of Poria cocos extract, 1-3 parts of cinnamon extract, 3-8 parts of Alpinia oxyphylla extract and 1-3 parts of ginseng extract; Preferably, in parts by weight, the Chinese medicine composition comprises 15 parts of Polygonatum odoratum extract, 7.5 parts of yam extract, 5 parts of Poria cocos extract, 1.5 parts of cinnamon extract, 5 parts of Alpinia oxyphylla extract and 1.5 parts of ginseng extract.

5. The Chinese medicine composition according to claim 3, characterized in that: The extract is a decoction extract.

6. The Chinese medicine composition according to claim 3, characterized in that: The dosage form of the Chinese medicine composition is an oral dosage form, preferably a granule, an oral liquid, a tablet, a syrup or a paste; Preferably, the granules are prepared by wet granulation; Preferably, the wetting agent for wet granulation is an ethanol solution with a mass fraction of 90-95%, preferably an ethanol solution with a mass fraction of 95%.

7. The method for preparing the Chinese medicine composition according to any one of claims 3 to 6, characterized in that: The following steps are involved: Decoct the wine polygonatum, yam, poria, cinnamon bark, alpinia oxyphylla and ginseng in water according to corresponding proportions, combine the medicinal liquids, filter and concentrate.

8. The preparation method according to claim 7, characterized in that: The decoction is performed 1 to 2 times, with 8 to 12 times the amount of water added for the first time and decoction for 1 to 2 hours; and 6 to 8 times the amount of water added for the second time and decoction for 1 to 2 hours; Preferably, the concentration is reduced pressure concentration; Preferably, the concentration is to obtain a clear paste with a relative density of 1.15-1.20; Preferably, the filtration is centrifugal filtration or plate and frame filtration.

9. The preparation method according to claim 8, characterized in that: The yield of the clear paste is in the range of 25-35%.

10. Use of the Chinese medicine composition according to claim 1 or claim 3 in the preparation of a medicament for treating and / or alleviating mild cognitive impairment.

Images