Brain function improver made from theanine

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

[Technical field]

[0001] The present invention relates to a brain function improver comprising theanine, and a composition containing the same, particularly a food and drink composition. [Background technology]

[0002] In recent years, as the aging of the population progresses, cognitive impairment of the brain associated with aging has become a social problem, and various researches are being conducted on foods, ingredients, etc. that are effective in preventing or improving cognitive impairment. The presence or absence of cognitive impairment 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 and performed. Patent Document 1 proposes improving cognitive function using a composition containing docosahexaenoic acid, uridine, etc., and describes the use of a mini-mental state test as a standard test for evaluating cognitive ability.

[0003] Other known methods for testing cognitive function include the Hasegawa Dementia Scale-Revised and the Cognitrax test. Patent Document 2 describes a method for evaluating the effectiveness of green tea ingredients for mild cognitive impairment using the Cognitrax test.

[0004] Patent Document 3 discloses that green tea leaf powder containing theanine and catechin is effective in maintaining cognitive function in healthy individuals or improving mild cognitive impairment through the Cognitrax test. On the other hand, Non-Patent Document 1 discloses that the combination of theanine and caffeine improves cognitive function, but theanine alone does not have such an effect. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2015-143248 A [Patent Document 2] JP 2020-038156 A [Patent Document 3] JP 2020-037540 A [Non-patent literature]

[0006] [Non-Patent Document 1] 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. Summary of the Invention [Problem to be solved by the invention]

[0007] However, because brain functions are extremely complex and various functions interact with each other, there is a demand for drugs, supplements, and food and beverage products such as beverages and tea leaf products that are specifically designed to improve specific brain functions, in particular functional foods.

[0008] The present invention has been made in consideration of the above problems, and aims to provide a novel brain function improver or a composition containing the same, particularly a food and drink composition. [Means for solving the problem]

[0009] Cognitive function testing methods differ not only in sensitivity and specificity, but also in the cognitive functions evaluated due to differences in evaluation methods. For example, the Revised Hasegawa Dementia Scale and the Mini-Mental State Examination, which evaluate cognitive function by totaling the scores of individual items such as reciting numbers backwards and calculation problems, have biases in the test content and point allocation, and the types of dementia that are easy to detect (Alzheimer's type, cerebrovascular type, etc.) are different. It has also been reported that it is difficult to detect abnormalities in subjects with mild symptoms of cognitive decline.

[0010] Unlike the conventional Revised Hasegawa Dementia Scale and Mini-Mental State Examination, the Cognitrax test has the advantage of being able to individually determine areas of impaired function.

[0011] The inventors discovered that even when assessed using the same Cognitrax test, matcha and each of the components contained in it contribute to improving cognitive functions in different ways, and thus completed the present invention.

[0012] That is, the present invention includes the following inventions. [1] A brain function improving agent comprising theanine, wherein the brain function is working memory or sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test. [2] The brain function improving agent according to [1], wherein the working memory or sustained attention is a brain function not assessed by the Revised Hasegawa Dementia Scale or the Mini-Mental State Examination. [3] The brain function improving agent according to [1] or [2], wherein an 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] The brain function improving agent according to any one of [1] to [4], wherein the improvement in working memory or connectivity attention is an increase in the number of correct responses or a decrease in the number of incorrect responses in the 4-part sustained processing test of the Cognitrax test compared to when matcha is administered. [6] The brain function improving agent described in [5], wherein the 4-part sustained processing test is a test of memory for two pictures prior to randomly displayed pictures. [7] A composition comprising the brain function improving agent according to any one of [1] to [6]. [8] The composition described in [7], which is in the form of a beverage, food, supplement or pharmaceutical. [9] The composition described in [7] or [8], which is in the form of a liquid, powder, tablet or capsule.

[10] The composition according to any one of [7] to [9] for improving working memory or sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test. Effect of the Invention

[0013] By taking theanine alone, it is possible to improve brain functions that could not be assessed by the Revised Hasegawa Dementia Scale or Mini-Mental State Examination. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, the embodiments or implementations of the present invention will be described in detail, however, the present invention is not limited to these and various modifications are possible without departing from the gist of the present invention.

[0015] (brain function improver) In one embodiment, there is provided a brain function improving agent comprising theanine, wherein the brain function is working memory or sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test.

[0016] Dementia symptoms are diverse, including memory impairment, impaired judgment, disorientation, language disorder (aphasia), apraxia, agnosia, and impaired executive function. Mild cognitive impairment (MCI) is a gray zone stage between a healthy state and dementia. In other words, it is a state in which a problem with one of the cognitive functions (memory, decision-making, reasoning, execution, etc.) does not interfere with daily life.

[0017] The Cognitrax test is a cognitive function testing technology developed by CNS Vital Signs, a US company (Gualtieri CT, Johnson LG: Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol 2006;21:623-643.), and has the following characteristics, for example: -Measures a wide range of functional areas, including memory, attention, processing speed, and executive function. The results are quantified and displayed in comparison with age-standard values. -10 types of tests are provided, and you can select the test depending on the purpose of the inspection. By monitoring individual values ​​over time, it is possible to detect changes in memory and cognitive function. - Accurate and reliable measurements with millisecond sensitivity. Very low learning or ceiling effect.

[0018] The ten tests in the Cognitrax test are: 1. Verbal Memory Test (Verbal Memory (VBM)) 2. Visual Memory Test (VIM) 3. Finger Tapping Test (FTT) 4.SDC Test (Symbol Digit Coding (SDC)) 5. Stroop Test (ST) 6. Shifting Attention Test (SAT) 7. Continuous Performance (CPT) 8. Perception of Emotion (POET) 9. Reasoning Test (NVRT) 10. Four Part Continuous Performance (FPCPT)

[0019] The Four-Part Sustained Processing Test measures working memory and sustained attention. It consists of four parts: Part 1 tests simple reaction speed, Part 2 is a modified sustained processing test, Part 3 tests memory for the previous picture, and Part 4 tests memory for the previous two pictures.

[0020] As used herein, "working memory assessed by the 4-part sustained processing test of the Cognitrax test" refers to a part of cognitive function, a memory function (function) temporarily required for the purpose of performing a task while performing the task, and the mechanism (structure) or system (structure) that supports it, that is, a function of working memory, and refers to a brain function that cannot be evaluated by the Revised Hasegawa Brief Intelligence Scale or the Mini-Mental State Examination. In other words, "working memory assessed by the 4-part sustained processing test of the Cognitrax test" is different from the working memory function and other cognitive functions evaluated by the Revised Hasegawa Brief Intelligence Scale or the Mini-Mental State Examination.

[0021] As used herein, "sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test" refers to a brain function that is a part of cognitive function, the ability to maintain a consistent reaction behavior during sustained or repetitive activities, and cannot be assessed by the Hasegawa Dementia Scale-Revised or the Mini-Mental State Examination. In other words, "sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test" is different from cognitive function as assessed by the Hasegawa Dementia Scale-Revised or the Mini-Mental State Examination.

[0022] Examples of improvements in working memory or connectivity attention include an increase in the number of correct responses or a decrease in the number of incorrect responses in the 4-part sustained processing test of the Cognitrax test when administered matcha compared to matcha. Matcha, which is used as a comparison to confirm the effects of brain function improvers, is expected to contain approximately half the amount of theanine as the active ingredient theanine. For example, if the brain function improver contains 100 mg of theanine, this is equivalent to 4 g of matcha, so the matcha used as a comparison will be approximately 2 g in total, and contain approximately 50 mg of theanine.

[0023] Theanine, an active ingredient in brain function improvers, is an amino acid that is found in large amounts in plants such as tea plants. Theanine is a component that is found in large amounts in high-grade green teas such as gyokuro, matcha, and high-grade sencha, and is found in large amounts in the core of young shoots and one leaf, and is found highest in the first harvest. Theanine content of tea leaves grown under Ohishita (kabusecha: gyokuro, tencha, etc.) is high, and the theanine concentration of tea leaves can be increased by nitrogen fertilization. From the viewpoint of efficiency, it is preferable to extract theanine from tea leaves with an increased theanine content. Theanine can be isolated using a known method. Synthetic theanine may be used.

[0024] As used herein, theanine refers to L-glutamic acid-γ-ethylamide (L-theanine), but may also be other L- or D-glutamic acid-γ-alkylamides such as L-glutamic acid-γ-methylamide, D-glutamic acid-γ-ethylamide (D-theanine), or derivatives containing L- or D-glutamic acid-γ-alkylamide in the basic structure (for example, glycosides of L- or D-glutamic acid-γ-alkylamide), as long as the desired effect is achieved.

[0025] Since theanine is a white crystalline powder, the brain function improver may be in the form of a powder. However, the dosage form of the brain function improver is not limited to powder, and may be in other forms.

[0026] The brain function improving agent is enclosed in an appropriate container depending on the dosage form. In the case of a powder, it can be enclosed in a bag, a box, or a similar container. For example, the brain function improving agent may be enclosed in a package such as a tea bag, and examples of the shape of such a package include a square type, a triangular pyramid type (so-called Tetra Pak (registered trademark)), a rounded bag, a W-chamber type, etc. In addition, the brain function improving agent may be filled in a type of bag that is dripped like coffee by pouring water or hot water into the bag body.

[0027] The container may be made of any material known to those skilled in the art. Examples of the material include plastics and metals, and more specifically, polyester, nylon, polycarbonate, cellophane, polyethylene, polypropylene, aluminum, paper, cellulose fibers, natural fibers, polylactic acid, etc. For example, the container may be made of a cloth filter made of synthetic fibers or a nonwoven fabric filter.

[0028] The container may comprise a laminate film, preferably such a laminate film comprises an internal aluminium layer.

[0029] The brain function improving agent can be administered to a subject suffering from or suspected of having mild cognitive impairment, more specifically, to a human who needs to improve working memory or sustained attention. The age of the subject is not particularly limited, but is preferably middle-aged or elderly, 50 to 69 years old.

[0030] The dosage of the brain function improving agent is adjusted so that the effective amount of theanine is, for example, about 50 to 200 mg per day, preferably about 80 to 120 mg, more preferably about 100 mg. The above dosage may be a single dose administered once a day, or may be multiple doses administered 2 to 3 times a day. The above dosage may be appropriately increased or decreased depending on the age, pathology, and symptoms of the subject.

[0031] Theanine as an active ingredient is preferably blended alone in the brain function improving agent, but may be combined with other active ingredients known to have brain function improving effects, as long as the effect of improving brain function is not impaired. However, when combined with theanine, catechin and caffeine inhibit the effect of improving brain function of theanine, which is not preferable.

[0032] (composition)

[0033] In one embodiment, a composition comprising a brain function improving agent is provided.

[0034] The dosage form of the brain function improving agent or the composition containing it is not particularly limited, and the administration route can be appropriately determined by a person skilled in the art depending on the dosage form and the degree of 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.). Oral administration is preferred.

[0035] The composition may contain an excipient other than theanine as an active ingredient. The excipient may be a solid excipient generally used in pharmaceutical preparations. Examples of the excipient include starches such as cornstarch, wheat flour, and rice flour, sugars such as lactose, sucrose, mannitol, sorbitol, and white sugar, dextrin, precipitated silica, gelatin, cellulose, and methylcellulose. One or more of these excipients may be appropriately selected and used.

[0036] The composition may be in the form of a powder since theanine is a white crystalline powder.

[0037] A composition containing a brain function improver is prepared by adding fats and oils, seasonings, flavors, etc., as necessary, to theanine and, optionally, an excipient, and mixing them. The composition may be prepared and provided as a liquid, powder, capsule, or tablet, in which case it is easy to provide as a supplement, etc. As used herein, "liquid" refers to a liquid preparation based on a liquid medium such as water or oil, including syrup, etc. As used herein, "tablet" refers to the dosage form of not only tablets but also tablets including pills. For tablets, the form may be such that the contents cannot be distinguished by taste, such as sugar-coated tablets. Capsules that are generally used for pharmaceuticals, etc., can be used, and both hard capsules and soft capsules can be used. Hard capsules can be prepared by filling a sample into a capsule coating formed using, for example, gelatin, hydroxypropyl methylcellulose, etc. Soft capsules can be obtained by sandwiching a sample between sheets of gelatin to which a plasticizer such as glycerin has been added, and then pressing and molding.

[0038] The size and content of the capsules and tablets, as well as the number of servings per time, can be set so that the subject can take them without difficulty. In general, the intake conditions can be set so that the daily intake of theanine is about 50 to 200 mg, preferably about 80 to 120 mg, and more preferably about 100 mg.

[0039] The composition is preferably provided in the form of a food or drink, particularly a food for specified health uses or a functional food. The composition is expected to be taken by subjects suffering from or suspected of having mild cognitive impairment, more specifically, by people who need to improve their working memory or sustained attention, and therefore the composition can be used to improve the brain function of such subjects, particularly the working memory or sustained attention evaluated by the 4-part sustained processing test of the Cognitrax test, and preferably brain functions not evaluated by the Revised Hasegawa Dementia Scale or the Mini-Mental State Examination.

[0040] The active ingredient, theanine, is added to foods and beverages by sprinkling or placing it on the surface of the food or beverage, or by mixing it into the food or beverage and dissolving it therein.

[0041] As used herein, "food and drink" refers to processed foods, beverages, fruits and vegetables, and other items that are consumed. Examples of beverages include, but are not limited to, milk beverages, lactic acid bacteria beverages, soy milk; tea beverages such as green tea, black tea, barley tea, roasted green tea, brown rice tea, and blended tea; soft drinks, nutritional beverages, sports beverages, fruit beverages, vegetable juices, dairy beverages, alcoholic beverages, jelly beverages, and carbonated beverages; and other beverages and drink preparations. In the case of tea beverages, it is preferable to reduce the caffeine or catechin, or both, content relative to the theanine content, or to eliminate the caffeine or catechin, or both, content.

[0042] Examples of containers for filling the beverage include, but are not limited to, commonly used containers such as plastic bottles, cans, paper bottles, jars, etc. It is preferable to use a container that can be sealed after being filled.

[0043] Examples of foods include sweets such as cookies, biscuits, chocolate, cakes, puddings, ice cream, sherbet, waffles, wafers, pancakes, donuts, popcorn, castella, caramel, candy, chewing gum, and Japanese sweets; breads such as white bread, sweet bread, and other breads; noodles such as udon, hiyamugi, somen, buckwheat, Chinese noodles, spaghetti, macaroni, rice vermicelli, and harusame; processed meat foods such as hamburger steaks, ham, bacon, and sausages; and instant foods such as curry, ramen, and soup, but are not limited to these.

[0044] Among foods and beverages, it is preferable to add theanine to tea-related foods and beverages such as tea drinks, granulated tea, tea bags, and packed tea (leaf).

[0045] Alternatively, the composition may be prepared in the form of granules, emulsion, cream, etc., and provided as food such as seasoning, sauce, dressing, etc. Such foods can be easily handled by providing them in small portions appropriately packaged according to the amount to be taken per serving.

[0046] The number of times a day to be taken, the time of day to be taken (morning / afternoon, morning / afternoon / evening, relative to meals), the amount to be taken at one time, and the amount to be taken per day are appropriately set, so the green tea composition may be prepared in an easy-to-take form based on the set intake conditions. Theanine is preferably taken in the morning. The composition may be orally taken for about 10 weeks or more, preferably about 12 weeks or more.

[0047] The rate of people whose symptoms progress from mild cognitive impairment to dementia is said to be about 10% on average per year, which means that about 40% will progress to dementia after 5 years, so it is very important to prevent dementia by dealing with mild cognitive impairment early. Therefore, providing the market with green tea-related foods in a form that is effective in maintaining cognitive function or improving mild cognitive impairment is significant in terms of health and medical care.

[0048] (Treatment method) In one embodiment, there is provided a method for improving brain function in a subject, comprising administering to the subject a brain function-improving agent comprising theanine, wherein the brain function is working memory or sustained attention as assessed by the 4-part sustained processing test of the Cognitrax test.

[0049] The subjects to whom the brain function improving agent is administered are those who suffer from or are suspected of having mild cognitive impairment, more specifically, those who need to improve their working memory or sustained attention. The age of the subjects is not particularly limited, but is preferably middle-aged or elderly, aged 50 to 69 years.

[0050] The dosage is adjusted so that the effective amount of theanine is, for example, about 50 to 200 mg per day, preferably about 80 to 120 mg, more preferably about 100 mg. The above dosage may be a single dose administered once a day, or may be multiple doses administered two to three times a day. The above dosage may be appropriately increased or decreased depending on the age, pathology, and symptoms of the subject.

[0051] The timing of administration is not limited, but it is preferably administered in the morning. The administration period is about 10 weeks or more, preferably about 12 weeks or more.

[0052] As long as theanine's effect of improving brain function is not impaired, it may be used in combination with drugs that are known to improve brain function. EXAMPLES

[0053] The present invention will be described in more detail below using examples and comparative examples, but the present invention is not limited to the following examples.

[0054] Preparation of brain function improver L-theanine (trade name: Suntheanine, Taiyo Kagaku Co., Ltd.) with a purity of 98% or more was used as a brain function improver. 100.6 mg of L-theanine was filled into a hard size 1 pork gelatin capsule (manufactured by Sansho Pharmaceutical Co., Ltd.) and used in the following test. The placebo was prepared in the same capsule as the L-theanine, and cornstarch was used as the excipient for both theanine and placebo capsules.

[0055] subject Sixty-nine healthy Japanese male and female subjects aged 50 to 69 years were recruited. The Mini-Mental State Examination-Japanese (MMSE-J) was administered to the selected 69 subjects, and 52 subjects who met the inclusion criteria of an MMSE-J score of 24 or more, and did not meet the exclusion criteria of currently receiving medication or treatment and having food allergies, were finally enrolled in the study.

[0056] Study design The study was a randomized, double-blind, parallel-group comparative study. The primary outcome measures were the results of the Japanese version of the Mini-Mental State Examination and the Cognitrax test, and the secondary outcome measures were the blood concentrations of amyloid beta 1-40 (Aβ(1-40)), amyloid beta 1-42 (Aβ(1-42)), secreted amyloid beta precursor protein alpha (sAPPα), amyloid beta precursor protein 770 (APP770), and brain-derived neurotrophic factor (BDNF). Using a computer-generated stratified randomization scheme (Huma R&D Co., Ltd.), subjects were assigned to the placebo or L-theanine group, taking into account age, sex, and MMSE-J score. A flow diagram of this study is shown in Figure 1.

[0057] Participants were asked to take one capsule of either placebo or L-theanine daily after breakfast for 12 weeks. During the study period, participants were restricted from taking any health foods, supplements, or medications that may affect cognitive function. Besides these restrictions, participants were instructed to maintain their usual lifestyle.

[0058] Evaluation items The evaluation scheme for the clinical trial is shown in Table 1 below. [Table 1] On the day of the test, the evaluations marked with a circle in the table above were carried out. The tests were carried out in the order shown in the table. * Blood samples were taken for blood tests (white blood cell count, red blood cell count, hemoglobin concentration, hematocrit, platelet count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) and evaluation of biochemical blood parameters (total protein, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, lactate dehydrogenase, uric acid, urea nitrogen, total bilirubin, albumin, creatinine, fasting plasma glucose, glycated hemoglobin).

[0059] On the day of the single-dose study, the Cognitrax test began approximately 50 minutes after the capsule was taken. The study was conducted in the same order at week 12, except that the capsule was taken before the test. Blood tests and biochemical blood parameter measurements were conducted at baseline and week 12 at SRL Co., Ltd. as a safety evaluation.

[0060] Mini-Mental State Examination In this study, we used the Japanese version of the Mini-Mental State Examination (MMSE-J, Nippon Bunka Kagakusha). The MMSE-J consists of 11 items, including orientation to time, orientation to place, memorization, attention and calculation, recall, naming, repetition, three-step command, reading, writing, and drawing, and the evaluation is based on the total score of these items. In this test, two tests of attention and calculation from the above items, namely the backward spelling task and the serial sevens task, were used. The score of the backward spelling task was used to assign subjects to the placebo or theanine group.

[0061] Cognitrax Trials Cognitrax is a cognitive function testing service developed by the US company CNS Vital Signs (Morrisville, North Carolina) to measure both reaction time and number of responses. Test details are shown in Table 2. [Table 2-1] [Table 2-2] [Table 2-3]

[0062] Blood Biomarkers On the day of the study, subjects were placed on a diet restriction from 6 hours before arriving at the hospital until the completion of the study. Serum collection tubes were used to estimate BDNF levels, and disodium ethylenediaminetetraacetate 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. Measurements were performed using the kits at the following dilution rates: Aβ(1-42) blood samples were diluted 4-fold with the HumanAmyloid-β(FL)Assay Kit-IBL; sAPPα blood samples were diluted 4-fold with the sAPPα(high sensitivity)Assay Kit-IBL; APP770 blood samples were diluted 50-fold with the 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 due to imprecision. Table 9 shows the number of samples analyzed for each biomarker. Measurements were performed by Skylight Biotech Co., Ltd.

[0063] statistical analysis Each value is presented as the mean ± standard deviation (SD). Normality was tested with the Shapiro-Wilk test. If no significant difference was found, a t-test was used, and if a significant difference was found, a Mann-Whitney U test was used. Statistical analyses were 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). To account for the multiplicity of tests, the significance level of differences between conditions was adjusted to p < 0.05 / 3 = 0.017 by Bonferroni correction.

[0064] result The final analysis included 24 patients in the placebo group (11 men, 13 women, mean age 57.9 ± 6.3 years) and 26 patients in the theanine group (12 men, 14 women, mean age 57.7 ± 4.8 years).

[0065] MMSE-J (Interactive Test) The mean scores on the MMSE-J (backwards task) performed before the intervention (baseline) were 27.7 ± 1.8 in the placebo group and 27.7 ± 1.4 in the theanine group. After 12 weeks of daily capsule intake, the scores were 28.3 ± 1.5 in the placebo group and 28.0 ± 1.6 in the theanine group. There were no significant differences in the MMSE-J between the theanine and placebo groups before and after the intervention.

[0066] Cognitrax test (computer-based cognitive function test) The Cognitrax tests were performed in the following order: VBM, VIM, FTT, SDC, ST, SAT, CPT, POET, NVRT, FPCPT, VBM, VIM. These tests assessed different cognitive functions. VBM and VIM assessed memory (Table 3). ST, SAT, CPT, and FPCPT parts 1 and 2 assessed attention (Table 4). POET assessed facial expression recognition (Table 5). FPCPT parts 3 and 4 assessed working memory (Table 6). SDC and NVRT assessed visual information processing (Table 7). FTT assessed motor function (Table 8).

[0067] [Table 3] VBM, Verbal Memory test; VIM, Visual Memory test. Values ​​are shown as mean ± standard deviation.

[0068] [Table 4] 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 with Bonferroni correction. Values ​​are presented as mean ± standard deviation.

[0069] [Table 5] POET, Perception of Emotions test. Values ​​are shown as mean ± standard deviation.

[0070] [Table 6] FPCPT, Four-Part Continuous Performance Test. Values ​​are presented as mean ± standard deviation. *p < 0.05 / 3 = 0.017 vs. placebo group. P values ​​were calculated using the Mann-Whitney U test with Bonferroni correction.

[0071] [Table 7] SDC, Symbol Digit Coding Test; NVRT, Non-Verbal Reasoning Test. Values ​​are shown as mean ± standard deviation.

[0072] [Table 8] FTT, Finger Tapping Test Values ​​are shown as mean ± standard deviation.

[0073] The first VBM and VIM performed represented immediate memory, and the last represented delayed memory. There was a 50-minute interval between the first and last VBM and VIM performed.

[0074] Memory Task The number of correct hits and correct passes in VBM and VIM were not significantly different between the theanine and placebo groups (Table 3). L-theanine did not affect memory either acutely or after chronic ingestion.

[0075] Attention Task In the single-dose study, ST (part 1) reaction times were significantly shorter in the theanine group than in the placebo group (Table 4), meaning that a single dose of L-theanine was sufficient to improve attention.

[0076] Facial expression recognition task Positive emotions (calm and happy) and negative emotions (sad and anger) were assessed with the POET. Results included three types of values: the sum of positive and negative emotions, the sum of positive emotions, and the sum of negative emotions. There were no significant differences in the number of correct answers or reaction times between the placebo and theanine groups (Table 5). Thus, it was revealed that L-theanine does not affect emotional judgments after either acute or chronic intake.

[0077] Working Memory Tasks In the single-dose FPCPT (Part 4), the theanine group had a significantly higher percentage of correct answers and significantly lower omission errors than the placebo group. In the FPCPT (Part 4), compared to baseline, the change in mean incorrect response time on the single-dose trial was significantly lower in the theanine group than in the placebo group (Table 6). After a single dose, L-theanine affected the quality of working memory, resulting in faster reaction times and more accurate answers.

[0078] Visual information processing tasks There was no significant difference in the number of correct answers or reaction times between the placebo and theanine groups (Table 7), indicating that L-theanine did not affect visual information processing after acute or chronic ingestion.

[0079] motor function There was no significant difference between the theanine and placebo groups in the mean number of right and left hits in the FTT (Table 8), indicating that L-theanine does not affect motor function after either acute or chronic intake.

[0080] Blood Biomarkers There were no significant differences between the theanine and placebo groups in plasma amyloid beta 1-40, amyloid beta 1-42, and the ratio of Aβ 1-40 / Aβ 1-42. Also, no significant differences were observed between the two groups in terms of sAPPα, APP770, and BDNF levels (Table 9).

[0081] [Table 9] Values ​​are shown as mean ± standard deviation.

[0082] Comparative Example A similar randomized, double-blind, parallel-group comparative study was also conducted on matcha tea containing theanine, caffeine, and catechin. Samples were prepared in the same manner as capsules filled with theanine, and capsules were filled with theanine (50.3 mg), caffeine (72.5 mg), and catechin (171 mg) in amounts equivalent to 2 g of matcha. Of the catechins included, 110 mg was derived from epigallocatechin gallate.

[0083] Similar to the theanine study, this study recruited healthy Japanese men and women aged 50 to 69 years, and 62 subjects who did not meet the exclusion criteria were assigned to either a placebo or matcha group.

[0084] The subjects took either a placebo or matcha capsule, nine per day, after breakfast for 12 weeks. The results showed that the theanine intake increased correct responses in the four-part sustained processing test of the Cognitrax test, and Number of correct answers missed No decrease was observed.

Claims

1. A brain function improving agent comprising theanine, the brain function being working memory as assessed by part 4 of the 4-part sustained processing test of the Cognitrax test; an improvement in working memory is defined as an increase in the number of correct responses or a decrease in the number of missed correct responses in part 4 of the 4-part sustained processing test of the Cognitrax test compared to when matcha was administered; A brain function improver, wherein the effective amount of theanine contained in the brain function improver is 50 to 200 mg per day as a single dose.

2. The brain function improving agent according to claim 1, wherein the working memory is a brain function not assessed by the Revised Hasegawa Dementia Scale or the Mini-Mental State Examination.

3. 2. The brain function improving agent according to claim 1, wherein part 4 of the 4-part sustained processing test is a test of memory for two pictures prior to randomly displayed pictures.

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