JP2022060055A - Brain function improver composed of theanine - Google Patents

Abstract

To provide a novel brain function improver or the like.SOLUTION: The present invention discloses a brain function improver composed of theanine, wherein the brain function means working memory or continuous attention evaluated in accordance with "Four Part Continuous Performance" of Cognitrax testing.SELECTED DRAWING: None

Description

The present invention relates to a brain function improving agent composed of theanine, a composition containing the theanine, particularly a food and drink composition, and the like.

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 ameliorating 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.

In addition, the revised Hasegawa's Dementia Scale-Revised and the Cognitolux test are known as methods for testing cognitive function. In Patent Document 2, the Cognitive Dementia test is used for mild cognitive impairment. A method for evaluating the effectiveness of green tea ingredients is described.

Patent Document 3 discloses that green tea leaf powder containing theanine and catechin is effective for maintaining cognitive function of healthy subjects or improving mild cognitive impairment through the Cognitolux test. On the other hand, Non-Patent Document 1 describes that the combination of theanine and caffeine improves cognitive function, but theanine alone does not have such an effect.

Japanese Unexamined Patent Publication No. 2015-143248 Japanese Unexamined Patent Publication No. 2020-038156 Japanese Unexamined Patent Publication No. 2020-037540

Kelly et al., "L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance", J Nutr. 2008 Aug; 138 (8): 1572S-1577S.

However, the function of the brain is very complicated, and various functions act in relation to each other. In particular, the provision of functional foods is required.

The present invention has been made in view of the above problems, and an object of the present invention is to provide a novel brain function improving agent or a composition containing the same, particularly a food or drink composition.

The cognitive function test method may differ not only in sensitivity and specificity, but also in the cognitive function evaluated due to the difference in the evaluation method. For example, the revised Hasegawa dementia scale and the Mini-Mental State Examination, which evaluates cognitive function based on the total score of the results of individual items such as reverse recitation of numbers and calculation problems, are easy to detect due to bias in test content and score allocation. There is also a report that it is difficult to detect abnormalities in subjects with different types of dementia (Alzheimer's type, cerebrovascular type, etc.) and mild symptoms of cognitive decline.

Unlike the conventional revised Hasegawa dementia scale and the Mini-Mental State Examination, the Cognitoracx test is characterized by being able to individually determine areas of reduced function.

The present inventors have found that matcha and each component contained therein contribute to the improvement of different cognitive functions even when evaluated by the same Cognitoracs test, and have completed the present invention.

That is, the present invention includes the following inventions.
[1]
A brain function improver consisting of theanine, which is an active memory or sustained attention agent whose brain function is evaluated in a 4-part continuous treatment test of the Cognitax test.
[2]
The brain function improving agent according to [1], wherein the working memory or sustained attention is a brain function that is not evaluated by the revised Hasegawa simple intelligence evaluation scale or the Mini-Mental State Examination.
[3]
The brain function improving agent according to [1] or [2], wherein the effective amount of theanine is 50 to 200 mg per day.
[4]
The brain function improving agent according to [3], wherein the effective amount of theanine is a single dose.
[5]
Improvements in working memory or connectivity attention are an increase in the number of correct responses or a decrease in the number of false responses in the 4-part continuous treatment test of the Cognitoracs test compared to when matcha was administered, [1] ] To the brain function improving agent according to any one of [4].
[6]
The brain function improving agent according to [5], wherein the 4-part continuous treatment test is a memory test of the figure two sheets before the figure displayed at random.
[7]
A composition containing the brain function improving agent according to any one of [1] to [6].
[8]
The composition according to [7], which is in the form of a beverage, food, supplement or pharmaceutical product.
[9]
The composition according to [7] or [8], which is in the form of a liquid, a powder, a tablet or a capsule.
[10]
The composition according to any one of [7] to [9] for improving operational memory or sustained attention evaluated in a 4-part continuous treatment test of the Cognitoracs test.

Taking theanine alone can improve brain function that could not be assessed by the revised Hasegawa Dementia Scale or the Mini-Mental State Examination.

Hereinafter, embodiments or embodiments of the present invention will be described in detail, but the present invention is not limited thereto, and various modifications can be made without departing from the gist thereof.

(Brain function improving agent)
In one embodiment, there is provided a brain function improver consisting of theanine, the brain function improver, the brain function of which is the working memory or sustained attention assessed by the 4-part continuous treatment test of the Cognitax test. To.

Symptoms of dementia range from memory impairment, impaired judgment, disorientation, speech impairment (aphasia), apraxia, agnosia, and executive dysfunction. Mild Cognitive Impairment (MCI) is a gray zone stage between healthy and dementia. That is, even if there is a problem in one of the cognitive functions (memory, decision, reasoning, execution, etc.), there is no problem in daily life.

The Cognitive Tracks test is a cognitive function test technology developed by CNS Vital Signs of the United States (Gualtieri CT, Johnson LG: Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol 2006; 21: 623- 643.), For example, it has the following features.
-Measure a wide range of functional areas such as memory, attention, processing speed, and executive function, and display the results by digitizing and comparing with age standard values.
・ 10 types of tests are provided, and the test can be selected according to the inspection purpose.
・ It is possible to detect changes in memory and cognitive function by monitoring individual values over time.
・ Accurate and reliable measurement with millisecond sensitivity.
-Very low learning effect and ceiling effect.

The 10 types of tests for the Cognitax test are as follows.
1. 1. Language Memory Test (Verbal Memory (VBM))
2. 2. Visual Memory Test (VIM)
3. 3. Finger tapping (FTT)
4. SDC test (Symbol Digit Coding (SDC))
5. Stroop Test (ST)
6. Attention Shift Test (Shifting Attention (SAT))
7. Sustained processing test (Continuous Performance (CPT))
8. Facial expression recognition test (Perception of Emotion (POET))
9. Logical Thinking Test (Reasoning (NVRT))
10.4 Part Continuous Processing Test (Four Part Continuus Performance (FPPCT))

The 4-part continuous treatment test measures working memory and sustained attention. The test consists of four parts: Part 1 examines the simple reaction rate, Part 2 examines the variant of the continuous processing test, Part 3 examines the memory of the previous figure, and Part 4 examines the memory of the previous figure. ..

As used herein, "working memory evaluated in the 4-part continuous processing test of the Cognitax test" is part of cognitive function and is temporary for the purpose of performing the task during the task. Required memory functions (functions), mechanisms (mechanisms) and systems (structures) that support them, that is, working memory functions that cannot be evaluated by the revised Hasegawa simple intelligence evaluation scale or the Mini-Mental State Examination. means. In other words, the "working memory evaluated by the 4-part continuous processing test of the Cognitax test" is different from the working memory function and other cognitive functions evaluated by the revised Hasegawa simple intelligence evaluation scale or the Mini-Mental State Examination.

As used herein, "persistent attention as assessed by the Cognitax test's four-part continuous treatment test" is part of cognitive function and is during sustained or repetitive activity. It means the ability to sustain a certain reaction behavior and means brain function that cannot be evaluated by the revised Hasegawa simple intelligence evaluation scale or the Mini-Mental State Examination. In other words, "sustainable attention evaluated by the 4-part continuous treatment test of the Cognitax test" is different from the cognitive function evaluated by the revised Hasegawa simple intelligence evaluation scale or the mini-mental state examination.

As an example of improvement in working memory or connectivity attention, an increase in the number of correct responses or the number of false responses in the 4-part continuous treatment test of the Cognitax test compared to the case where matcha was administered in comparison with matcha. There is a decrease in. Matcha as a comparison, which is used to confirm the effect of the brain function improving agent, is expected to contain about half the amount of theanine as the active ingredient, theanine. For example, when the brain function improving agent theanine is 100 mg, this is an amount equivalent to 4 g of matcha, so that the total amount of matcha to be compared is about 2 g, and the theanine contained therein is about 50 mg.

Theanine, which is an active ingredient of a brain function improving agent, is an amino acid that is abundantly contained in plants such as tea plant. Theanine is a component that is abundantly contained in high-grade green tea such as gyokuro, matcha, and high-grade sencha. In addition, the theanine content of tea leaves cultivated under cover (kabusecha: gyokuro, tencha, etc.) is high, and it is possible to increase the theanine concentration of tea leaves by fertilizing with nitrogen. From the viewpoint of efficiency, it is preferable to extract theanine from tea leaves having an increased theanine content. Isolation of theanine can be performed using known techniques. Theanine may be a synthetic product.

As used herein, "theanine" means L-glutamic acid-γ-ethylamide (L-theanine), but other L-glutamic acid-γ-methylamide, D- as long as it produces the desired effect. Derivatives containing L- or D-glutamic acid-γ-alkylamide, L- or D-glutamic acid-γ-alkylamide such as glutamic acid-γ-ethylamide (D-theanine), D-glutamic acid-γ-methylamide in the basic structure ( For example, a glycoside of L- or D-glutamic acid-γ-alkylamide, etc.) may be used.

Since theanine is a white crystalline powder, the brain function improving agent may be in the form of a powder. However, the dosage form of the brain function improving agent is not limited to the powder form, and may be another form.

The brain function improving agent is encapsulated in an appropriate container according to the dosage form. In the case of powder, it can be enclosed in a bag, a box, or a similar container. For example, a brain function improving agent may be encapsulated in a package such as a tea bag, and the shape of such a package may be, for example, a square shape, a triangular pyramid shape (so-called Tetra Pak (registered trademark)), or a round shape. Examples include a bag body, a W chamber type, and the like. Alternatively, water or hot water may be poured into the bag body to fill a drip-type product such as coffee with a brain function improving agent.

As the material of the container, a material known to those skilled in the art can be used. Examples thereof include plastics and metals, and specific examples thereof include polyester, nylon, polycarbonate, cellophane, polyethylene, polypropylene, aluminum, paper, cellulose fibers, natural fibers and polylactic acid. For example, it may be made of a cloth filter made of synthetic fibers or the like, or it may be made of a non-woven fabric filter.

The container may include a laminated film. It is preferable that such a laminated film has an aluminum layer inside.

Brain function improvers can be administered to subjects who have or are suspected of having mild cognitive impairment, more specifically to humans in need of improved working memory or sustained attention. The age of the subject is not particularly limited, but is preferably middle-aged and older, 50 to 69 years old.

The dose of the brain function improving agent is adjusted, for example, so that the effective amount of theanine is about 50 to 200 mg, preferably about 80 to 120 mg, and more preferably about 100 mg per day. The above-mentioned dose may be a single dose once a day, or may be a plurality of doses 2 to 3 times a day. The above amount can be appropriately increased or decreased depending on the age, pathological condition and symptoms of the subject.

Theanine as an active ingredient is preferably blended alone in a brain function improving agent, but may be combined with other active ingredients known to have a brain function improving effect as long as the brain function improving effect is not impaired. .. However, catechin and caffeine are not preferable when combined with theanine because they inhibit the brain function improving effect of theanine.

(Composition)

In one embodiment, a composition comprising a brain function improving agent is provided.

The dosage form of the brain function improving agent or the composition containing the same is not particularly limited, and the administration route can be appropriately determined by a person skilled in the art according to the dosage form and the degree of the brain function improving agent to be improved, for example, oral. Administration or parenteral administration (intravenous, intraarterial, subcutaneous, intradermal, intramuscular, or intraperitoneal injection, transdermal, nasal, transmucosal, etc.) can be mentioned. Oral administration is preferred.

The composition may contain excipients in addition to theanine as an active ingredient. 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. From such excipients, one kind or two or more kinds can be appropriately selected and used.

Since theanine is a white crystalline powder, the composition may be in the form of a powder.

A composition containing a brain function improving agent is prepared by adding and mixing theanine and optionally an excipient with oils and fats, seasonings, fragrances and the like, if necessary. The composition may be prepared and provided as a liquid, a powder, a capsule, or a tablet, and in this case, it is easy to provide as a supplement or the like. As used herein, the "liquid agent" is a liquid preparation based on a liquid medium such as water or oil, and includes syrup and the like. As used herein, "tablet" means not only a tablet but also a dosage form of a tablet containing pills. The tablet may be in a form such as a sugar-coated tablet whose contents cannot be discriminated by taste. 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. The hard capsule can be prepared by filling a capsule film formed with, for example, gelatin, hydroxypropylmethyl cellulose or the like with a sample. 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.

The size and content of capsules and tablets, and the number of ingestions per dose can be set so that the subject can take them reasonably. In general, the intake conditions can be set such that the daily intake of theanine is about 50-200 mg, preferably about 80-120 mg, more preferably about 100 mg.

The composition is preferably provided in the form of food or drink, particularly food for specified health use or functional food. The composition is intended to be ingested by subjects who have or are suspected of having mild cognitive impairment, more specifically, humans who need improvement in working memory or sustained attention. The use of the object is to improve brain function of those subjects, especially working memory or sustained attention evaluated in the 4-part continuous treatment test of the Cognitolux test, preferably the revised Hasegawa simple intelligence evaluation scale or mini. Brain function that is not evaluated by the mental state examination can be mentioned.

Theanine, which is an active ingredient, is added to foods and drinks by sprinkling it on the surface of foods and drinks, placing it on the surface of foods and drinks, or mixing and dissolving it in foods and drinks.

As used herein, "food and drink" means food and drink such as processed foods, beverages, fruits and vegetables. Examples of beverages are dairy beverages, lactic acid bacteria beverages, soy milk; tea beverages such as green tea, tea, wheat tea, roasted tea, brown rice tea, blended tea, soft beverages, nutritional beverages, sports beverages, fruit beverages, vegetable juices, dairy beverages, etc. There are, but are not limited to, palatable beverages and drinks such as alcoholic beverages, jelly beverages, and carbonated beverages. In the case of tea beverages, it is preferable to reduce the content of caffeine and / or catechin relative to the content of theanine, or remove the content of caffeine and / or catechin.

Examples of containers for filling beverages include, but are not limited to, commonly used containers such as PET bottles, cans, paper and bottles. It is preferable to use a container that can be sealed after being filled.

Examples of foods include cookies, biscuits, chocolates, cakes, puddings, ice creams, sherbets, waffles, wafers, hot cakes, donuts, popcorn, castella, caramel, candy, chewing gum, Japanese sweets and other sweets; bread, sweet buns, etc. Breads such as bread; noodles such as udon, cold barley, somen, buckwheat, Chinese soba, spaghetti, macaroni, beefun, and harusame; processed meat foods such as hamburger, ham, bacon, and sausage; instants such as curry, ramen, and soup. Examples include, but are not limited to, foods.

Among the foods and drinks, it is preferable to add theanine to tea-related foods and drinks such as tea beverages, granulated tea, tea bags, and packed tea (leaf).

Alternatively, the composition may be prepared in the form of fine granules, emulsion, cream or the like and provided as foods such as seasonings, sauces and dressings. It is easy to handle such foods if they are appropriately divided and packaged according to the amount of intake per serving.

Since 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 are set appropriately, the set intake conditions It is advisable to prepare a green tea composition in a form that is easy to ingest. Theanine is preferably taken in the morning. The composition may be orally ingested for about 10 weeks or longer, preferably about 12 weeks or longer.

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, so it is mild. It is very important to realize the prevention of dementia by early coping with cognitive impairment. Therefore, it is significant in terms of health and medical care to provide the market with green tea-related foods in a form effective for maintaining cognitive function or improving mild cognitive impairment.

(Method of treatment)
In one embodiment, a method of improving a subject's brain function, comprising administering to the subject a brain function improving agent consisting of theanine, the brain function is assessed in a four-part continuous treatment test of the Cognitolux test. A method, which is operational memory or sustained attention, is provided.

Subjects who are expected to receive brain function improving agents are those who have or are suspected of having mild cognitive impairment, and more specifically, humans who need improvement in operational memory or sustained attention. .. The age of the subject is not particularly limited, but is preferably middle-aged and older, 50 to 69 years old.

The dose is adjusted, for example, so that the effective amount of theanine is about 50-200 mg, preferably about 80-120 mg, more preferably about 100 mg per day. The above-mentioned dose may be a single dose once a day, or may be a plurality of doses 2 to 3 times a day. The above amount can be appropriately increased or decreased depending on the age, pathological condition and symptoms of the subject.

The timing of administration is not limited, but it is preferably given in the morning. The administration period is about 10 weeks or more, preferably about 12 weeks or more.

As long as theanine does not impair the effect of improving brain function, it may be used in combination with a drug known to have an effect of improving brain function.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. The present invention is not limited to the following examples.

Preparation of brain function improving agent As a brain function improving agent, L-theanine (trade name: Santheanine, Taiyo Kagaku Co., Ltd.) having a purity of 98% or more was used. 100.6 mg of L-theanine was packed in a hard No. 1 size pig gelatin capsule (manufactured by Sansei Pharmaceutical Co., Ltd.) and used in the following tests. Placebo was dispensed in the same capsules as L-theanine and cornstarch was used as an excipient for both theanine and placebo capsules.

subject
We recruited 69 subjects from healthy Japanese men and women aged 50 to 69 years. A Japanese version of the Mini-Mental State Examination (MMSE-J) was performed on 69 selected subjects, met the selection criteria of an MMSE-J score of 24 or higher, and is currently receiving drug therapy or treatment. Fifty-two subjects who did not meet the exclusion criteria of having food allergies were finally enrolled in the study.

Study design studies were conducted in a randomized, double-blind, parallel-group comparative study. The primary endpoint is the results of the Japanese version of the minimal state test and the Cognitolux test, and the secondary endpoints are amyloid β1-40 (Aβ (1-40)) and amyloid β1-42 (Aβ (1-42)). ), Secretive amyloid β precursor protein α (sAPPα), amyloid β precursor protein 770 (APP770) and brain-derived neurotrophic factor (BDNF) in the blood. Using a computer-generated stratified randomization schema (Huma R & D, Inc.), subjects were assigned to placebo or L-theanine groups, taking into account age, gender, and MMSE-J score. The flow chart of this study is shown in Figure 1.

Subjects took placebo or L-theanine capsules 1 tablet daily for 12 weeks after breakfast. During the test period, subjects were restricted from taking health foods, supplements, or drugs that could affect cognitive function. Besides these restrictions, subjects were instructed to maintain a normal lifestyle.

試験当日は、上記表中の丸印の評価を実施した。検査は表に示す順序で実施した。
* 採血は血液検査（白血球数、赤血球数、ヘモグロビン濃度、ヘマトクリット、血小板数、平均赤血球容積、平均赤血球ヘモグロビン、平均赤血球ヘモグロビン濃度）及び生化学的血液パラメータ（総タンパク質、トリグリセリド、総コレステロール、高密度リポタンパクコレステロール、低密度リポタンパクコレステロール、アルカリホスファターゼ、アスパラギン酸アミノトランスフェラーゼ、アラニンアミノトランスフェラーゼ、γ-グルタミルトランスペプチダーゼ、乳酸脱水素酵素、尿酸、尿素窒素、総ビリルビン、アルブミン、クレアチニン、空腹時血糖値、糖化ヘモグロビン）の評価のために実施した。 Evaluation items The evaluation schemes for clinical trials are shown in Table 1 below.

On the day of the test, the circles in the above table were evaluated. The tests were performed in the order shown in the table.
* Blood sampling includes blood tests (leukocyte count, red blood cell count, hemoglobin concentration, hematocrit, platelet count, average red blood cell volume, average red blood cell hemoglobin, average red blood cell hemoglobin concentration) and biochemical blood parameters (total protein, triglyceride, total cholesterol, high density). Lipoprotein cholesterol, low density lipoprotein cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, lactic acid dehydrogenase, uric acid, urea nitrogen, total bilirubin, albumin, creatinine, fasting blood glucose level, It was carried out for the evaluation of saccharified hemoglobin).

On the day of the single dose test, the Cognitoracs test was started about 50 minutes after the capsule was ingested. The tests were performed in the same order during the 12th week, except that the capsules were taken before taking the test. Blood tests and biochemical blood parameter measurements were performed at baseline and at week 12 at SRL Co., Ltd. as a safety assessment.

Mini-Mental State Examination In this study, we used MMSE-J (Nippon Bunka Kagaku Co., Ltd.), which is the Japanese version of the Mini-Mental State Examination. The MMSE-J consists of 11 items in total: orientation about time, orientation about place, memorization, attention and calculation, reproduction, name, repeat, 3-step instruction, reading, writing, and drawing. It is done with the total score. In this test, two tests of attention and calculation among the above items, that is, a backward spelling task and a serial sevens task, were adopted. The score of the backward spelling task was used to assign subjects to the placebo or theanine group.

Cognitive Tracks Test
Cognitrax is a cognitive function testing service developed by the US company CNS Vital Signs (Morrisville, NC) to measure both reaction time and response count. The details of the inspection are shown in Table 2.

On the day of the blood biomarker test, subjects were restricted from eating 6 hours before arrival at the hospital until the test was completed. Serum blood collection tubes were used to estimate BDNF levels, and ethylenediaminetetraacetic acid disodium tubes were used to measure Aβ (1-40), Aβ (1-42), sAPPα, and APP770. After collection, blood was centrifuged at 3000 rpm and dispensed into 1.5 ml Eppendorf tubes. The measurements were made using the kit at the following dilutions: Blood samples of Aβ (1-42) were diluted 4-fold with Human Amyloid-β (FL) Assay Kit-IBL. Blood samples of sAPPα were diluted 4-fold with the sAPPα (high sensitivity) assay kit IBL. Blood samples of APP770 were diluted 50-fold with Human APP770 Assay Kit-IBL. BDNF blood samples were diluted 20-fold with the Human BDNF ELISA Kit (Quantikine-R & D Systems). Measurements below the range of the kit were excluded as they were inaccurate. Table 9 shows the number of samples analyzed for each biomarker. The measurement was carried out by Skylight Biotech Co., Ltd.

Statistical analysis Each value is shown as mean ± standard deviation (SD). Normality was tested by the Shapiro-Wilk test. If no significant difference was found, the t-test was used, and if no significant difference was found, the Mann-Whitney U test was used. Statistical analysis was performed at baseline, during the single dose study, and at week 12. Data were analyzed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Considering the multiplicity of tests, the significance level of the difference between the conditions was adjusted to p <0.05 / 3 = 0.017 by the correction by the Bonferroni method.

Results The final analysis was performed on 24 patients in the placebo group (11 males, 13 females, average 57.9 ± 6.3 years) and 26 in the theanine group (12 males, 14 females, average 57.7 ± 4.8). Was).

MMSE-J (interactive test)
Mean scores for the MMSE-J (backwards task) performed prior to the intervention (baseline) were 27.7 ± 1.8 in the placebo group and 27.7 ± 1.4 in the theanine group. The scores after daily capsule intake for 12 weeks were 28.3 ± 1.5 in the placebo group and 28.0 ± 1.6 in the theanine group. There was no significant difference in MMSE-J between the theanine and placebo groups before and after the intervention.

Cognitrax test (PC-based cognitive function test)
The Cognitrax test was performed in the order VBM, VIM, FTT, SDC, ST, SAT, CPT, POET, NVRT, FPCPT, VBM, VIM. These tests evaluated a variety of cognitive functions. VBM and VIM evaluated memory (Table 3). ST, SAT, CPT, and FPCPT Part 1 and Part 2 evaluated attention (Table 4). POET evaluated facial expression recognition (Table 5). FPCPT Part 3 and Part 4 evaluated working memory (Table 6). SDC and NVRT evaluated visual information processing (Table 7). FTT evaluated motor function (Table 8).

VBM, Verbal Memory test; VIM, Visual Memory test.
値は平均値±標準偏差として示す。

VBM, Verbal Memory test; VIM, Visual Memory test.
Values are shown as mean ± standard deviation.

ST, Stroop Test; SAT, Shifting Attention Test; CPT, Continuous Performance Test; FPCPT, Four- Part Continuous Performance Test.
* p < 0.05/3 = 0.017 vs プラセボ群。P値は、Mann-Whitney U検定及びボンフェローニ補正を用いて計算した。値は平均値±標準偏差として示す。

ST, Stroop Test; SAT, Shifting Attention Test; CPT, Continuous Performance Test; FPCPT, Four- Part Continuous Performance Test.
* p <0.05 / 3 = 0.017 vs placebo group. P-values were calculated using the Mann-Whitney U test and Bonferroni correction. Values are shown as mean ± standard deviation.

POET, Perception of Emotions test.
値は平均値±標準偏差として示す。

POET, Perception of Emotions test.
Values are shown as mean ± standard deviation.

FPCPT, Four-Part Continuous Performance Test.
値は平均値±標準偏差として示す。* p < 0.05/3 = 0.017 vs プラセボ群。P値は、Mann-Whitney U検定及びボンフェローニ補正を用いて計算した。

FPCPT, Four-Part Continuous Performance Test.
Values are shown as mean ± standard deviation. * p <0.05 / 3 = 0.017 vs placebo group. P-values were calculated using the Mann-Whitney U test and Bonferroni correction.

SDC, Symbol Digit Coding Test; NVRT, Non-Verbal Reasoning Test.
値は平均値±標準偏差として示す。

SDC, Symbol Digit Coding Test; NVRT, Non-Verbal Reasoning Test.
Values are shown as mean ± standard deviation.

FTT, Finger Tapping Test
値は平均値±標準偏差として示す。

FTT, Finger Tapping Test
Values are shown as mean ± standard deviation.

The first VBM and VIM performed show immediate memory and the last memory shows delayed memory. There was a time of about 50 minutes between the first VBM and VIM and the last VBM and VIM.

Memory task
The number of correct hits and correct passes for VBM and VIM was not significantly different between the theanine and placebo groups (Table 3). L-Theanine did not affect memory either after acute or chronic ingestion.

Attention Task In the single-dose study, ST (Part 1) reaction time was significantly shorter in the theanine group than in the placebo group (Table 4). That is, a single dose of L-theanine was sufficient to improve attention.

Facial expression recognition task
POET evaluated positive emotions (calmness and happiness) and negative emotions (sadness and anger). Results include the following three values: the sum of positive and negative emotions, the sum of positive emotions, and the sum of negative emotions. There was no significant difference in the number of correct answers or reaction times between the placebo and theanine groups (Table 5). Therefore, it was revealed that L-theanine did not affect emotional judgment either after acute or chronic ingestion.

In the working memory task single-dose FPCPT (Part 4), the theanine group had a significantly higher accuracy rate and significantly lower dropout error than the placebo group. In FPCPT (Part 4), the change in mean inaccurate response time in the single-dose study was significantly lower than in the placebo group of theanine group compared to baseline (Table 6). After a single ingestion, L-theanine affected the quality of working memory, shortened reaction time and provided a more accurate answer.

There was no significant difference in the number of correct answers or reaction time between the visual information processing task placebo group and the theanine group (Table 7). Therefore, it can be seen that L-theanine did not affect visual information processing after acute or chronic ingestion.

There was no significant difference in the mean number of right and left FTT hits between the motor function theanine and placebo groups (Table 8). Therefore, it can be seen that L-theanine does not affect motor function either after acute or chronic ingestion.

The ratios of blood biomarkers plasma amyloid β1-40, amyloid β1-42, and Aβ1-40 / Aβ1-42 were not significantly different between the theanine and placebo groups. In addition, no significant difference was observed between the two groups in terms of sAPPα, APP770, and BDNF levels (Table 9).

値は平均値±標準偏差として示す。

Values are shown as mean ± standard deviation.

Comparative Example A randomized, double-blind, parallel-group comparative study similar to the above was also performed on matcha containing theanine, caffeine, and catechin. The sample was prepared in the same manner as the capsule filled with theanine, and the capsule was filled with theanine (50.3 mg), caffeine (72.5 mg), and catechin (171 mg) in an amount equivalent to 2 g of matcha. Of the catechins compounded, 110 mg is derived from epigallocatechin gallate.

Similar to theanine, the study recruited subjects from healthy Japanese men and women aged 50 to 69 years and assigned 62 subjects who did not meet the exclusion criteria to the placebo or matcha group.

Subjects took placebo or matcha capsules 9 tablets daily for 12 weeks after breakfast. As a result, in the 4-part continuous treatment test of the Cognitax test, no increase in correct response or decrease in false response confirmed by taking theanine was confirmed.

Claims (10)

A brain function improver consisting of theanine, which is an active memory or sustained attention agent whose brain function is evaluated in a 4-part continuous treatment test of the Cognitax test. The brain function improving agent according to claim 1, wherein the working memory or sustained attention is a brain function that is not evaluated by the revised Hasegawa simple intelligence evaluation scale or the Mini-Mental State Examination. The brain function improving agent according to claim 1 or 2, wherein the effective amount of theanine is 50 to 200 mg per day. The brain function improving agent according to claim 3, wherein the effective amount of theanine is a single dose. Claim that the improvement in working memory or connectivity attention is an increase in the number of correct responses or a decrease in the number of false responses in the 4-part continuous treatment test of the Cognitoracs test compared to when matcha was administered. The brain function improving agent according to any one of 1 to 4. The brain function improving agent according to claim 5, wherein the 4-part continuous treatment test is a test of memory of the previous two figures with respect to a randomly displayed figure. A composition comprising the brain function improving agent according to any one of claims 1 to 6. The composition according to claim 7, which is in the form of a beverage, food, supplement or pharmaceutical product. The composition according to claim 7 or 8, which is in the form of a liquid, a powder, a tablet or a capsule. The composition according to any one of claims 7 to 9, for improving operational memory or sustained attention as assessed by the 4-part continuous treatment test of the Cognitax test.