JP7101087B2 - How to evaluate the effectiveness of green tea ingredients for mild cognitive impairment - Google Patents

Description

The present invention relates to a method for evaluating the effectiveness of a green tea component for mild cognitive impairment, which is useful in product design of foods and drinks using a green tea material expected to improve or prevent mild cognitive impairment.

It has been reported that tea catechins contained in green tea are effective in preventing heart disease and cancer, and as the health effects of tea catechins become clear, active intake of tea catechins is becoming widespread. Along with this, beverages with an increased content of tea catechins are on the market. In addition, due to growing health consciousness, various functional ingredients contained in tea extracts such as catechins are in high demand as ingredients for health foods and supplements.

In recent years, with the progress of aging, cognitive dysfunction of the brain associated with aging has become a social problem, and various studies have been conducted on foods, ingredients, etc. that are effective in preventing or improving cognitive dysfunction. The presence or absence of cognitive dysfunction in humans can be diagnosed by a cognitive function test (screening test), and various cognitive function tests have been proposed. Therefore, in the evaluation of cognitive function, an appropriate test is appropriately selected from known cognitive function tests according to the purpose of the test. Patent Document 1 proposes to improve cognitive function by using a composition containing docosahexaenoic acid, uridine, etc., and describes the use of the Mini-Mental State Examination as a standard test for evaluating cognitive ability. There is. Further, Patent Document 2 below describes various secondary measurements as tests for measuring the improvement of mild cognitive impairment by administration of docosahexaenoic acid.

Japanese Patent Publication No. 2014-534226 Japanese Unexamined Patent Publication No. 2015-143248

The cognitive function test includes tests for a wide variety of items, and it is thought that more precise tests can be performed if tests are performed for many types of items. However, if a uniform inspection is performed for many types of items, it takes time and effort, and it takes time. In addition, in the investigation of the effectiveness of oral ingestion of foods and drinks, the ingestion period until the effectiveness is manifested tends to be long, so from the viewpoint of product development, it is necessary to make the inspection as efficient as possible. desired.

An object of the present invention is to provide an evaluation method capable of efficiently evaluating the effectiveness of a green tea component for mild cognitive impairment (MCI), thereby improving mild cognitive impairment using the green tea component as an active component. Or to support the design and development of products for prevention.

In order to solve the above problems, the present inventors have conducted diligent research, and as a result, the test period (ingestion period) required for the effect of the green tea component to appear in the cognitive function test tends to differ depending on the test item. By using this, it became possible to construct a simple inspection and evaluate the effectiveness efficiently, and the present invention was completed.

According to one aspect of the present invention, the method for evaluating the effectiveness of the green tea component for mild cognitive impairment is to evaluate at least one of the attention shift test, the facial expression cognitive test, and the 4-part continuous treatment test in the Cognitive Tracks test. A subject who was adopted as a test and had a score of 20 to 30 points by the mini-mental state test was subjected to the above-mentioned predetermined evaluation test, and the subject was allowed to ingest a sample containing a green tea component for at least 4 weeks, and the sample was used. The gist is to perform the predetermined evaluation test again on the subject after ingestion and evaluate the improvement effect of mild cognitive impairment by comparing the results of the predetermined evaluation test before and after ingestion of the sample.

Further, according to another aspect of the present invention, the method for evaluating the effectiveness of the green tea component for mild cognitive impairment prescribes at least one of the attention shift test, the stroop test and the 4-part continuous treatment test in the Cognitive Tracks test. The subject who had a score of 20 to 30 points by the Mini-Mental State Examination was subjected to the above-mentioned predetermined evaluation test, and the subject was allowed to ingest a sample containing a green tea component for at least 12 weeks. The gist is to perform the predetermined evaluation test again on the subject after ingesting the sample, and evaluate the improvement effect of mild cognitive impairment by comparing the results of the predetermined evaluation test before and after ingesting the sample.

In the above evaluation method, it is advisable to have the subject ingest the sample so that the intake of the green tea component is 2.0 g / day. Further, the subject after ingesting the sample is subjected to the mini-mental state examination again, and the effect of maintaining or improving the function of a healthy person is evaluated by comparing the results of the mini-mental state examination before and after ingesting the sample. be able to. Further, the age of the subject can be selected so as to be 50 to 89 years old. If a subject having a score of 27 to 30 points by the Mini-Mental State Examination and an age of less than 57 years is selected as the subject, the effectiveness can be suitably evaluated.

According to the evaluation method of the present application, the effectiveness of the sample for mild cognitive impairment can be evaluated easily and efficiently, and the design of a product for improving or preventing mild cognitive impairment using green tea as an active ingredient is supported and developed. Can be promoted. Thereby, it is possible to provide an excellent product containing a green tea component simply and at an appropriate cost.

With the progress of research on the prevention and treatment of cognitive dysfunction, improvement of mild cognitive impairment (MCI: Mild Cognitive Impairment) using the components contained in green tea leaves is expected. Mild cognitive impairment is a gray zone stage between healthy and dementia, and even if one of the cognitive functions (memory, decision, reasoning, execution, etc.) has a problem, daily life There is no problem with this.

Green tea leaves contain various components, including hydrophilic components that can be ingested as beverages, lipophilic components obtained as extracts, and insoluble or sparingly soluble components such as fibers that make up tea leaves. Is done. Extensive basic research is required to elucidate the mechanism of action that improves cognitive (mental function) disorders for one component. Moreover, in the intake of green tea components as food and drink, not only the components expected to be effective at present, but also the various components contained in the green tea leaves as described above can obtain the effect of improving cognitive dysfunction. There is a possibility, and the effect of combining multiple components is also possible. Therefore, it is rational to examine the cognitive function of the subject before and after ingestion of the sample containing the green tea component and judge the effectiveness of the sample based on the comparison of the results before and after ingestion. ..

Providing green tea-related foods to the market in a highly effective form is significant in terms of health and medical care. However, the quality of green tea leaves varies depending on the variety of tea leaves, cultivation method, picking time, processing conditions, etc., and the component content also varies. In addition, there is a difference in the absorption of components depending on the form of ingestion of food and drink. In such a situation, it is important to promptly evaluate the improvement effect of cognitive impairment in order to accurately select raw materials and design products.

The diagnosis of mild cognitive impairment can be made by a cognitive function test (screening test), and various cognitive function tests have been proposed. Typical cognitive function tests include the revised Hasegawa Simple Intelligence Evaluation Scale (HDS-R) and the Mini-Mental State Examination (MMSE). In addition to these, MoCA-J (Japanese version of Montreal Cognitive Assessment), Mini-Cog, CANTAB VRM, PRM, SOC, SWM, DASC-21 (dementia assessment sheet in community-based comprehensive care system), Cognitrax ) Etc. are also available. Also available is the Five Cog test, which screens for age-related cognitive decline (AACD), a concept of mild cognitive impairment.

Symptoms of dementia range from memory impairment, impaired judgment, disorientation, speech impairment (aphasia), apraxia, agnosia, and executive dysfunction. For this reason, the cognitive function test as described above includes various test items related to characters, figures, colors, time, place, etc., and tests are carried out for thinking, reasoning, judgment, adaptation, problem solving, etc. To. When the present inventors attempted to investigate the improvement effect of the green tea component on mild cognitive impairment using a cognitive function test, it was found that the period during which the effect of the green tea component was manifested tended to differ depending on the test item. That is, by selecting a specific test item, it is possible to shorten the inspection period for determining the presence or absence of an effect.

In the present application, a specific test item is selected from the test items included in the cognitive function test, and the subject's cognitive function test is performed on the selected test. This makes it possible to shorten the inspection period to about 4 weeks. In general, in order to evaluate the effectiveness of a specific ingredient by a cognitive function test, it is possible to set a test period of several months to half a year, and in some cases, a year, so shortening the test period is a product design. It is very advantageous to proceed. Therefore, the method for evaluating the effectiveness of the green tea component for mild cognitive impairment in the present application can shorten the time required for product development by using it when designing a product containing the green tea component. In other words, it is useful as a simple evaluation method that supports product design. The method for evaluating the effectiveness of the green tea component for mild cognitive impairment will be specifically described below.

In the method for evaluating the effectiveness of the green tea component for mild cognitive impairment, a specific test included in the Cognitoracs test is used as a predetermined evaluation test for evaluation. The Cognitax test is a test developed by CNS Vital Signs of the United States based on the existing cognitive function test, and includes the following 10 types of tests. These tests allow measurements in a wide range of functional areas such as memory, attention, processing speed, and execution function, and the measurement results are measured values such as the number of answers, the number of incorrect answers, the reaction time, and their age. It is displayed by the standardized score calculated by comparing with the standard value.

1) Language memory test (VBM: Verbal Memory): A test for language learning, word memory, and word recognition. The memory function of a word is measured by the response to find the displayed word from a new group of words. Tests are performed immediately after memorization and after a certain period of time to evaluate short-term memory and long-term memory.
2) Visual Memory Test (VIM): A test for visual learning, geometry memory, and geometry recognition. The memory and cognitive function of a figure is measured by the response to find the already displayed figure from a new group of figures. Tests are performed immediately after memorization and after a certain period of time to evaluate short-term memory and long-term memory.
3) Finger tapping test (FTT: Finger Tapping): A test related to motion speed and fine motion control. Measure the number of keystrokes with your index finger.
4) SDC test (Symbol Digit Coding): A test for information processing speed, complex attention, and visual perception speed. Measure the ability to respond to numbers corresponding to symbols based on the symbol-number correspondence table.
5) Stroop Test (ST): A test for executive function, simple or complex reaction speed, compromise between speed and accuracy, information processing speed, suppression or disinhibition. Based on the meaning and color of the characters, measure the speed and accuracy of responding according to the conditions for the displayed characters.
6) Attention Shifting Attention (SAT): A test related to executive function, reaction speed, information processing speed, and speed-accuracy trade-off. Based on the shape and color of the geometric figure, measure the speed and accuracy of responding according to randomly changing conditions.
7) Continuous Performance (CPT): A test for continuous attention, selective reaction rate, and impulsivity. Measures long-term attention retention in response to text display.
8) Facial expression cognitive test (POET: Perception of Emotions): A test for social cognitive brain, emotional judgment, and selective reaction time. Measure the judgment about the match between the displayed facial expression and emotion.
9) Logical thinking test (or non-verbal logical thinking test, NVRT: Non-Verbal Reasoning): A test for theoretical assembly, theoretical cognition, and cognitive speed. From the three figures drawn in the three sections, the figure that should be in one empty section is inferred, and the understanding of information, the inference ability, and the cognitive ability of the conceptual relationship are measured by the result.
10) 4-Part Continuous Performance (FPCPT: 4-Part Continuous Performance): A test for continuous attention and operational memory. The simple reaction rate and long-lasting response to the display of the figure, and the memory of the already displayed figure are measured.

After the cognitive function test was performed on the subject, the subject was ingested a sample containing the green tea component, and the cognitive function test was repeatedly performed on the subject during the ingestion period. You can check the change over time. That is, it is possible to know the correlation between the intake period of the sample and the cognitive function of the subject. Using each test of the Cognitax test to examine the time course of the subject's cognitive function due to sample intake, the time course of cognitive function tends to differ depending on the type of test. In other words, the intake period in which the effect of improving cognitive function by the green tea component is manifested differs depending on the type of test.

Of the above 10 tests, the attention shift test, facial expression cognitive test, and 4-part continuous treatment test showed improvement in cognitive function after ingestion for about 4 weeks, and other tests showed improvement. difficult. In addition, after ingestion for about 12 weeks, improvement in cognitive function can be observed in the attention shift test, the Stroop test, and the 4-part continuous treatment test. In this way, the choice of test to be performed affects the efficiency of evaluating the sample by the cognitive function test, so if the test to be adopted is properly selected, the effectiveness of the sample can be efficiently judged and the food and drink product. It can be reflected in the design.

In the method for evaluating the effectiveness of the green tea component for mild cognitive impairment in the present application, a specific test of the above-mentioned Cognitoracs test is adopted as a predetermined evaluation test in order to evaluate an efficient sample through ingestion by a subject. At this time, it is possible to set two forms in which the test options to be adopted differ depending on the intake period by the subject. As a first form, as a predetermined evaluation test, at least one of the attention shift test, the facial expression cognitive test, and the four-part continuous treatment test in the Cognitorac test is adopted, and the period during which the subject ingests the sample is at least. It is set to be 4 weeks. As a second form, as a predetermined evaluation test, at least one of the attention shift test, the Stroop test, and the 4-part continuous treatment test in the Cognitorac test is adopted, and the period during which the subject ingests the sample is at least 12 It is set to be a week. There may be a plurality of tests to be selected as a predetermined evaluation test, and the larger the number of tests to be selected, the more material is required to judge the effectiveness of the sample.

In addition, it is considered that the above-mentioned test can be substituted by another test having similar evaluation contents, and does not exclude the replacement by the existing test and the test to be developed in the future. For example, the above-mentioned attention shift test can be expected to be a substitute for the TMT (Trail Making Test) test for evaluating attention function and executive function.

As described above, the ingestion period of the sample and the predetermined evaluation test are determined and the sample is provided to the subject, and the subject starts ingesting the sample containing the green tea component and ingests the sample over the above period. The subjects are those who can evaluate the improvement in mild cognitive impairment, and middle-aged and elderly people who are aware of the decline in cognitive function are selected in advance. The age of the subject is preferably 50 to 89 years. Subjects under the age of 57 tend to be more likely to detect manifestations of efficacy in the test. When selecting a subject, it is advisable to perform screening by a mini-mental state examination and select a subject having a score of 20 to 30 points, preferably 27 to 30 points by the examination. It is preferable to select the subject by selecting the serial 7 task in the "Caution and calculation" item of the examination. Subjects corresponding to mild cognitive impairment may be selected by the other dementia screening tests described above. For example, in HDS-R, a score of 14 to 24 points is applicable. Alternatively, an MCI screening test that measures proteins in blood may be utilized.

Regarding the intake of the sample, it is preferable to divide the subject into a sample administration group and a placebo administration group and perform a control test by a single-blind method or a double-blind method. In that case, the number of subjects is generally about 6 or more, preferably about 10 to 50. The subjects should be sorted so that there is no difference between the sample administration group and the placebo administration group in terms of the subject's age, gender, MMSE score score, height, average body weight, and standard deviation as much as possible. Is desirable.

Subjects selected according to the above are given the sample ingestion period, sample or placebo determined above. It is advisable to conduct a two-group parallel test so that there is no difference due to the difference in intake period (timing). A sample (or placebo) is provided to the subject and the subject is allowed to ingest under constant intake conditions for at least 4 weeks (or at least 12 weeks).

The content and ingestion conditions of the sample ingested by the subject can be appropriately set according to the design concept of the food and drink product. Therefore, the sample is prepared based on the composition content of the tea component determined based on the product design. The sample provided to the subject is ingested under the determined ingestion conditions. As intake conditions, the number of daily intakes and the time of intake (morning / afternoon, morning / day / night, relationship with meals), the amount of one intake and the amount of daily intake, and those that can be taken at the same time ( The type and amount of water, etc.) are set. The size and content (ingredient composition) of the sample and the number of samples per ingestion are determined so that the subject can ingest it reasonably. Generally, the intake condition can be set so that the daily intake of green tea components (green tea extract, green tea leaf powder) is about 40 mg to 10 g. As a standard, it is good to set the intake condition so that about 2 g of green tea component is ingested per day. For example, the intake condition is set so that the daily intake of green tea component is ingested once in the morning. be able to. Based on the set intake conditions, it is advisable to prepare the sample in a form that is easy to ingest.

Samples can be prepared and provided in capsules or tablets such as tablets and pills. The tablet preparation may be in a form such as a sugar-coated tablet that can prevent the taste of the contents from being discriminated. As the capsule, those generally used for pharmaceutical products and the like may be used, and either hard capsules or soft capsules can be used. Hard capsules can be prepared by filling a capsule film formed with, for example, gelatin, hydroxypropylmethyl cellulose, etc. with a sample, and if necessary, a pharmaceutically acceptable excipient is placed in the capsule. May be added. The soft capsule is obtained by sandwiching a sample with a sheet material obtained by adding a plasticizer such as glycerin to gelatin and performing pressure-bonding molding. As the excipient, a solid one generally used for a pharmaceutical preparation may be used. Examples thereof include starches such as cornstarch, wheat flour and rice flour, sugars such as lactose, sucrose, mannitol, sorbitol and sucrose, dextrin, precipitated silica, gelatin, cellulose and methylcellulose. For placebo, instead of the green tea component, it is advisable to use an excipient colored green with a coloring agent such as gardenia pigment. In addition, seasonings, fragrances, and the like may be blended into the sample and placebo within a pharmaceutically acceptable range so that the green tea component cannot be discriminated.

The green tea component blended in the sample when preparing the sample in the above-mentioned form may be any of green tea leaves, green tea extract and extraction residue, and may be powder, coarse particles, liquid, gel and viscous fluid. It can be used in the form of. The green tea component can be added to the excipient to form a sample, and the blending form and the amount of the green tea component can be appropriately set according to the set intake conditions. Further, if necessary, commonly used materials such as pharmaceutically acceptable additives may be added.

The components contained in green tea leaves include water-soluble components, hydrophobic (lipophilic) components, and insoluble or sparingly soluble components. Water-soluble components include catechins (catechin (C), galocatechin (GC), epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG)), and complex tannins. , Flavonol, caffeine, complex polysaccharides, water-soluble vitamins such as vitamin B ₂ and vitamin C, theanine, γ-aminobutyric acid, saponin, soluble dietary fiber (pectin), minerals and the like. The lipophilic component includes β-carotene, vitamin E, chlorophyll and the like, and the insoluble or sparingly soluble component includes insoluble dietary fiber, protein, mineral and the like. Kabusecha grown in the dark has a high content of epigallocatechin gallate and theanine. The green tea component as described above contains a large number of components having an antioxidant function and useful for suppressing aging, and the usefulness of catechins in suppressing cancer has been reported. The effects of caffeine and saponin on the central nervous system are also known.

The digestion and absorption of such green tea components can vary depending on the conditions ingested. For example, lipophilic components are relatively easily absorbed in the presence of fats and oils, and decomposition of easily decomposable components may be suppressed by fibers and fats and oils having an inclusion function and a film-forming ability. That is, the digestion and absorption at the time of ingestion differ depending on the state of the green tea component in the prepared sample, which may affect the effect of improving cognitive function. For example, powdered tea and tea extract may have different effects. Therefore, considering the above points in the preparation of samples and the analysis of evaluation results may help elucidate the mechanism of action.

After the subject has finished ingesting the sample (or placebo that does not contain green tea) during the set ingestion period, the subject after ingesting the sample is subjected to the prescribed evaluation test again to obtain the result of the evaluation test. do. Then, the presence or absence of an improvement effect on mild cognitive impairment is determined by comparing the results of the evaluation test before and after ingestion of the sample. As a result, the effectiveness of the green tea component contained in the sample ingested by the subject was evaluated, and based on this evaluation, the direction was confirmed or changed in the design of the product containing the green tea component for the purpose of improving mild cognitive impairment. You can proceed.

The endpoints of the 10 Cognitoracs tests differ in their associated brain function. In the Cognitax test, the intake period in which the effect of improving cognitive function by the green tea component appears differs depending on the type of test, and the difference in the intake period in which the effect appears is due to the mechanism by which the green tea component acts on brain function. It seems to be related. In other words, this is considered to be a peculiar property in the use of the green tea component. Attention shift test, facial expression cognitive test and 4-part continuous treatment test can evaluate the effectiveness of the sample by ingestion for about 4 weeks, so the effectiveness of the sample should be judged simply based on the evaluation in these tests. And the test period can be shortened.

If the intake of the sample containing the green tea component is further continued, the effect continues even after 12 weeks in the attention shift test and the 4-part continuous treatment test. On the other hand, there is the Stroop test as a test in which the ingestion period in which the effect is manifested exceeds 8 weeks. In the Stroop test, it is possible to evaluate the efficacy after ingestion for about 12 weeks.

Furthermore, it is meaningful to evaluate the effectiveness of the sample by performing the mini-mental state examination again on the subject after ingesting the sample together with the predetermined evaluation test. By comparing the results of the Mini-Mental State Examination before and after ingestion of the sample, the effect of maintaining or improving the function of healthy subjects can be evaluated.

When a green tea material such as matcha is used in the production of foods and drinks to be heated, thermal alteration of the green tea component occurs. When a sample is prepared using such a product and supplied to a subject, the evaluation method of the present application can be applied to evaluate the effect of improving the cognitive function of the green tea component in the product. Therefore, it can also be used as a means for evaluating the manufacturing conditions of a product and improving the manufacturing process.

The percentage of people who progress from mild cognitive impairment to dementia is said to be about 10% on average annually, which means that about 40% will progress to dementia after 5 years. In other words, the time required to evaluate the effectiveness of one ingredient or material leads to a loss of opportunity for symptom improvement in the subject. Therefore, shortening the time required to evaluate the improvement effect of mild cognitive impairment is important not only to support and promote product design but also to realize prevention of dementia by early detection of mild cognitive impairment. ..

A randomized, double-blind, two-group, parallel-group comparative study of the efficacy of green tea components for mild cognitive impairment was performed as follows.

<Preparation of sample and placebo>
As green tea ingredients, matcha (trade name: Hozen no Shiro, theanine content: 2.4% by mass, EGCG content: 5.3% by mass, total amount of 8 catechins: 8.4% by mass, caffeine content Amount: 3.5% by mass) was prepared. 2 g of matcha is added to 0.6 g of excipient (a mixture of partially pregelatinized starch, dextrin, calcium stearate, fine silicon dioxide) and mixed, and the mixture is evenly divided and filled into 9 gelatin capsules. By doing so, a sample for one ingestion was prepared.
In addition, a gardenia pigment was added to 2 g of the excipient (same as above) to color it green, and this was evenly divided and filled in 9 gelatin capsules to prepare a placebo for one ingestion.

<Selection of subjects>
The MMSE test was performed as a screening for 88 middle-aged and elderly subjects (50 to 69 years old) who were aware of cognitive decline. In the "Caution and calculation" item of the MMSE test, both the serial 7 task and the reverse recitation task were selected. For 77 subjects with a score of 22 points or more in the MMSE test (scores including the scores of the serial 7 tasks, excluding the points of the reverse-speaking task), 62 subjects (scores: 22 to 30 points) in order from the lowest score. Was selected and selected as the subjects to be evaluated by the following evaluation methods. Height, weight, pulse and blood pressure were measured for 62 subjects, and subject background surveys and interviews were conducted. Furthermore, 62 subjects were divided into two groups using the average age, sex ratio, and average score of the MMSE test as allocation factors, and the sample group and the placebo group were each composed of 31 subjects. Based on this group composition, the following evaluation tests were performed by ITT (Intent To Treat) analysis. In the placebo group, 2 subjects dropped out due to poor physical condition, and the number was 29. The subject composition of each group is shown in Table 1.

<Evaluation inspection>
Subjects in the sample and placebo groups were evaluated for cognitive function by performing 10 tests of the Cognitax test (provided by CNS Vital Signs). The contents of each test are as follows. For the results of each test, the number of responses is indicated by the mean ± standard deviation between the subjects, and the reaction time is indicated by the mean ± standard deviation between the subjects calculated from the reaction time per subject's response.

[Visual memory test]
Fifteen figures are displayed on the screen at a rate of once every two seconds, and then the existing figures are displayed together with the new 15 figures, and the existing figures are answered. Measure the number of correct answers for a predetermined number of tests (time required: about 3 minutes).

[Stroop test]
(1) Words (red, blue, yellow) are randomly displayed in black, respond immediately after seeing the display, and measure the time required for a predetermined number of responses (simple reaction time [milliseconds]). (2) Words (red, blue, yellow, green) are randomly displayed in color, and respond only when the color displaying the word matches the meaning of the word, or only when the meaning does not match. In a predetermined number of tests (time required: about 5 minutes), the number of erroneous responses (Stroop erroneous reaction) is measured.

[Caution shift test]
One figure (circle, triangle) is displayed at the top of the screen and two at the bottom (color is randomly red or blue), and the same figure or the same color as the top display is selected from the bottom to respond. .. The number of correct and incorrect answers in a predetermined number of tests (required time of about 3 minutes) and the reaction time (correct reaction time [milliseconds]) in the correct answer are measured.

[Facial expression recognition test]
The facial expression displayed on the screen responds with correctness regarding the match with the emotion displayed below it. In a 2-minute test, the reaction time [milliseconds] is measured. The number of correct answers and reaction time in each case of positive reaction and negative reaction, and the total number of correct answers of positive reaction and negative reaction, the average correct answer time, the total number of overlooked correct answers, and the total of false reactions are calculated.

[Nonverbal Logic Thinking Test]
From the figures displayed in three of the four sections on the screen, the figure to be included in the vacant section is inferred, and a response is made by selecting from the options. Measure the number of correct and incorrect responses in a predetermined number of tests (time required: about 3.5 minutes).

[4 part continuous processing test]
(1) Part 1: While characters are displayed randomly on the screen, respond immediately when a specific character is displayed, measure the response time [milliseconds] in the correct answer response, and calculate the average value. (2) Part 2: While the figure is displayed randomly on the screen, when a specific figure is displayed, an immediate response is made, the response time in the correct answer response is measured, and the average value is calculated. (3) While the figure is displayed randomly on the screen, if the previous figure is displayed, an immediate response is made, the response time in the correct answer response is measured, and the average value is calculated. (4) While the figures are displayed randomly on the screen, if the previous figure is displayed, an immediate response is made, the response time in the correct answer response is measured, and the average value is calculated.

[Continuous processing test]
While characters are displayed randomly on the screen, if a specific character is displayed, an immediate response is made, the number of false reactions in a predetermined test (required time is about 5 minutes) is measured, and the average value is calculated.

[Language memory test]
Fifteen words are displayed on the screen at a rate of one every two seconds, and then the existing words are displayed together with the new 15 words, and the existing words are answered. Measure the number of correct answers for a predetermined number of tests (time required: about 3 minutes).

[Finger tap test]
Hit the key as fast as possible for 10 seconds with the index finger of your right hand. Perform 3 times after 1 practice, and repeat the same work with the index finger of the left hand. The number of times the key is hit is measured, and the average value of the three times is obtained.

[SDC test]
At the top of the screen, a table showing eight symbols and eight numbers corresponding to each other is displayed, and at the bottom of the screen, a table having eight symbols and blanks is displayed. According to the correspondence in the upper table, the response time [milliseconds] in the work of filling in the blanks with the numbers corresponding to each symbol in the lower table is measured, and the correct answer and incorrect answer of the predetermined number of tests (required time about 4 minutes) are measured. Check the number of answers and the reaction time.

<Sample intake and evaluation of efficacy>
After this, the above-mentioned sample or placebo was provided to each subject in the sample group and the placebo group, and 9 samples (or placebo) were ingested once a day in the morning, and this was continued for 12 weeks. did. During this ingestion period, 10 tests of the Cognitax test were performed again at 4 weeks, 8 weeks and 12 weeks to test cognitive function. Table 2 shows the test results that are effective. The evaluation of the test result is based on the t-test or the Mann-Whitney U-test.
In addition, at the end of the 12-week intake, the MMSE test was performed again to test the cognitive function. The results are shown in Table 3.

In the test of Table 2 in the above-mentioned Cognitoracs test, an increasing tendency of the correct answer response and a decreasing tendency of the correct answer response time are observed in the sample group. Improvements in accuracy are seen in the attention shift test and nonverbal logic thinking test, and reaction time is shortened in the Stroop test, attention shift test, facial expression cognitive test, and 4-part continuous processing test.

In the test results, there is a tendency that the time when the effectiveness of the sample manifests during the ingestion period differs depending on the test. During the 4-week intake period, the efficacy was clearly confirmed in the attention shift test, the facial expression cognitive test, and the 4-part continuous processing test, and the effect was also confirmed in the nonverbal logic thinking test and the Stroop test. Therefore, these tests are suitable for sample evaluation in a short period of time, and the period of sample administration to a subject may be set to at least 4 weeks.

In addition, during the 12-week intake period, efficacy can be evaluated in the attention shift test, Stroop test, and 4-part continuous treatment test. The manifestation of the effect in these tests is relatively clear and suitable when the accuracy of sample evaluation is important. In this case, it is appropriate to set a period of at least 12 weeks for sample administration to the subject. However, in the attention shift test and the facial expression cognitive test, the effectiveness is manifested by ingestion for 4 weeks, and the appearance is relatively clear. Therefore, in these tests, even if ingested for 4 weeks, it is relatively relatively clear. It is possible to make an accurate evaluation.

As a tendency in the whole test, the effect of ingesting the green tea component tends to appear as an improvement in the simple response, and it is considered that it is effective in improving the function related to the reaction rate and the processing rate.

In the results of the MMSE test in Table 3, the effectiveness of ingestion of the green tea component is confirmed as a whole group. However, no significant difference was observed when classified by age with 57 years as the boundary, and effectiveness in men was recognized when classified by gender.

In order to compare and examine the above points, the results of the Stroop test, continuous treatment test, facial expression cognitive test, and 4-part continuous treatment test of the Cognitax test are displayed by age group starting from 57 years old, as shown in Table 4. become. The number of subjects was 15 in the placebo group under 57 years old, 13 in the placebo group over 57 years old, 14 in the sample group under 57 years old, and 16 in the sample group over 57 years old.

According to Table 4, the effectiveness is seen in the facial expression cognitive test and the 4-part continuous treatment test for subjects under 57 years old. The facial expression recognition test differs from Table 2 in that the reaction time for the correct response and the reaction time for the positive response are described. In other words, it can be said that the improvement effect is more likely to be obtained in the positive reaction than in the negative reaction. Even in the 4-part continuous treatment test, an improvement effect was observed in subjects under 57 years old. From this, it can be said that the effect of the green tea component, which appears as an improvement in a relatively simple response, becomes even more remarkable when the subject's age is specified to be less than 57 years old. This result means that items for which no significant difference is observed in the MMSE test can be evaluated in the Cognitoracs test.

Table 5 shows the results of the Stroop test and the 4-part continuous processing test of the Cognitax test according to the score classification of the MMSE test with 27 points as the boundary. The number of subjects was 13 in the placebo group with less than 27 points, 15 in the placebo group with 27 points or more, 14 in the sample group with less than 27 points, and 16 in the sample group with 27 points or more.

According to Table 5, in the subjects whose MMSE test score was 27 points or more, the improvement effect in the Stroop test and the 4-part continuous treatment test was clearly recognized, and the effect could also be recognized in the facial expression cognitive test. That is, it is easy to evaluate the effect of improving cognitive function by these tests in a subject whose cognitive function is relatively mildly deteriorated. Therefore, specifying the subject to some extent is a useful method for easily recognizing the manifestation of the effect in evaluating the effect of improving the cognitive function by the green tea component by using the Cognitax test.

Further, Table 6 shows the results of the visual memory test, the nonverbal logic thinking test, the attention shift test, and the 4-part continuous processing test of the Cognitoracs test by gender classification. The number of subjects was 10 for the male placebo group, 18 for the female placebo group, 13 for the male sample group, and 17 for the female sample group.

According to Table 6, some efficacy is observed in the 4-part continuous treatment test in both males and females.
Therefore, specifying the test items is significant in evaluating the effectiveness of the green tea component.

Since it is possible to support the design of products for the improvement or prevention of mild cognitive impairment using green tea ingredients as the active ingredient and promote the development, we decided to provide products containing excellent green tea ingredients at a simple and reasonable cost. I can contribute.

Claims (6)

At least one of the attention shift test, facial expression cognitive test and 4-part continuous processing test in the Cognitax test was adopted as the prescribed evaluation test.
Subjects with a score of 27 to 30 points by the Mini-Mental State Examination were subjected to the above-mentioned predetermined evaluation test before and after ingesting a sample containing a green tea component for 4 to 12 weeks .
A method for evaluating the effectiveness of a green tea component for cognitive function in a person with mild cognitive impairment or a healthy person , which evaluates the effect of improving cognitive function by comparing the results of the predetermined evaluation test before and after ingestion of a sample. Attention shift test, Stroop test and 4-part continuous processing test in Cognitolux test are adopted as the prescribed evaluation test.
Subjects with a score of 27 to 30 points by the Mini-Mental State Examination were subjected to the above-mentioned predetermined evaluation test before and after ingesting a sample containing a green tea component for 4 to 12 weeks .
A method for evaluating the effectiveness of a green tea component for cognitive function in a person with mild cognitive impairment or a healthy person , which evaluates the effect of improving cognitive function by comparing the results of the predetermined evaluation test before and after ingestion of a sample. The method for evaluating the effectiveness of a green tea component on the cognitive function of a person with mild cognitive impairment or a healthy person according to claim 1 or 2, wherein the subject ingests a sample so that the intake of the green tea component is 2.0 g / day. Further, the subject is subjected to the mini-mental state examination again after ingesting the sample, and the effect of maintaining or improving the cognitive function is evaluated by comparing the results of the mini-mental state examination before and after ingesting the sample. The method for evaluating the effectiveness of a green tea component for the cognitive function of a person with mild cognitive impairment or a healthy person according to any one of Items 1 to 3. The method for evaluating the effectiveness of a green tea component on the cognitive function of a person with mild cognitive impairment or a healthy person according to any one of claims 1 to 4, wherein the subject's age is 50 to 89 years. The method for evaluating the effectiveness of a green tea component on the cognitive function of a person with mild cognitive impairment or a healthy person according to any one of claims 1 to 4, wherein the subject is less than 57 years old.