JP7529255B2 - Composition for improving cognitive function speed - Google Patents

Description

The present invention relates to a composition used to improve cognitive function.

With the advent of an aging society, attention is being focused on brain health. It is said that improving diet is an effective way to maintain brain health. Various research is being conducted on compositions (such as food compositions) that can maintain brain health.

Patent Document 1 describes a food and drink for improving brain function that contains as an active ingredient a cinnamic acid derivative called 3-(4-hydroxy-3-methoxyphenyl)propionic acid.

In addition, Non-Patent Document 1 describes the possibility of ergothioneine as a brain food. Specifically, it describes that ergothioneine has a neurogenesis effect, that the neurogenesis effect promotes the metabolism of nerve cells and may be effective in memory and learning, and that when a novel object exploration test was performed using mice as an evaluation system for memory and learning, it was suggested that oral intake of ergothioneine improves memory and learning ability.

Patent No. 6236185

Masao Kato et al., "Ergothioneine as a transporter-mediated brain food," FOOD STYLE 21, 2017, Vol. 21, No. 2, pp. 21-24

However, the cognitive functions of the brain have not been fully elucidated. In the classification of neurocognitive disorders (NCDs) in the Diagnostic and Statistical Manual of Mental Disorders V (DSM-5), the cognitive function areas impaired in NCD patients are classified into six areas: "complex attention," "executive function," "learning and memory," "language," "perception-motor," and "social cognition." In the past, the effect of ergothioneine was suggested to be the improvement of memory and learning ability in these six areas. However, the effects of the other categories have not been elucidated. The DSM is a classification manual for mental illnesses and disorders created by the American Psychiatric Association, and is officially called the Diagnostic and Statistical Manual of Mental Disorders.

The object of the present invention is to provide a composition useful for improving cognitive functions other than memory and learning, and a method for producing the composition.

As a result of intensive research conducted by the present inventors to solve the above problems, they discovered that L-ergothioneine has the effect of improving cognitive function speed, the effect of improving verbal memory associated with aging, the effect of improving sustained attention associated with aging, and the effect of improving simple attention associated with aging. These findings led to the completion of the present invention.

The present invention relates to a composition for improving cognitive function speed, which contains L-ergothioneine as an active ingredient, or a composition for improving cognitive function speed, which contains Tamogitake extract as an active ingredient. L-ergothioneine may be contained in Tamogitake extract. Furthermore, the intake amount of L-ergothioneine can be 1 mg to 30 mg per adult per day. Furthermore, the present invention can improve the information processing speed in the brain as the cognitive function speed. Furthermore, in addition to the cognitive function speed, the composition can be used to improve verbal memory associated with aging, improvement of sustained attention associated with aging, or improvement of simple attention associated with aging.

In addition, in the present invention, the composition may be a food composition, in which case the food composition may be a health food, a functional food, a nutritional supplement, a supplement, a food for specified health uses, a food for the sick, a combination food for the sick, or a food for the elderly. The composition may also be a pharmaceutical composition. The composition may also be a composition consisting of Pleurotus cornucopiae extract, a freeze-dried composition, or a spray-dried composition.

The present invention provides a composition that is useful for improving cognitive functions other than memory and learning, and a method for producing the composition.

1 is a graph showing the results of the overall memory test in the Cognitrax test. 1 is a graph showing the results of a verbal memory test in the Cognitrax test. 1 is a graph showing the results of a visual memory test in the Cognitrax test. 1 is a graph showing the test results of cognitive function speed in the Cognitrax test. 1 is a graph showing the reaction speed test results in the Cognitrax test. 1 is a graph showing the test results of overall attention in the Cognitrax test. 1 is a graph showing the results of the cognitive flexibility test in the Cognitrax test. 1 is a graph showing the results of a processing speed test in the Cognitrax test. 1 is a graph showing the results of the Cognitrax test on executive function. 1 is a graph showing the results of a working memory test in the Cognitrax test. 1 is a graph showing the results of a sustained attention test in the Cognitrax test. 1 is a graph showing the test results of simple attention in the Cognitrax test. 1 is a graph showing the results of a motor speed test in the Cognitrax test.

The following describes in detail an embodiment of the present invention. Note that the following embodiment is merely an example of the present invention and is not intended to limit the scope of the present invention, its applications, or its uses.

[Composition for improving cognitive function speed]
The present embodiment is a composition for improving the cognitive function speed in the human brain (hereinafter, may be referred to as "the present improving composition"), which contains L-ergothioneine as an active ingredient. The present improving composition (food composition or pharmaceutical composition for improving cognitive function speed) can be used, for example, by orally ingesting it, in a method for improving the cognitive function speed of a patient who needs to improve their cognitive function speed. Note that the cognitive function speed refers to the speed at which the brain and body understand and react to information or objects (such as the information processing speed in the brain), and is correlated with the amount of physical activity as well as the amount of exercise.

The composition for improvement and the method for improving cognitive function speed are useful for improving the cognitive function speed of elderly people and people with mild dementia (MCI). They are also useful for improving the cognitive function speed of middle-aged people, young people, and minors. They are also useful for improving the cognitive function speed of animals other than humans (e.g., mammals such as dogs, cats, and monkeys).

The composition for improvement and the method for improving cognitive function speed are also useful for improving verbal memory and attention (sustained attention and simple attention) associated with aging. Therefore, verbal memory and attention can be improved in elderly and middle-aged people. The composition for improvement can be a composition consisting of Tamogitake extract (such as Tamogitake concentrate), a freeze-dried composition, or a spray-dried composition.

Here, L-ergothioneine is a type of amino acid that has the chemical structure of the following formula (1) in a crystalline state.

L-ergothioneine is known to become a tautomer with a thiol structure in solution, and is stable against heat and acid. In addition, L-ergothioneine is an antioxidant like ascorbic acid, and cannot be synthesized in the body and must be ingested from the outside. From the standpoint of digestibility, safety, taste, etc. in food and pharmaceutical applications, it is preferable to use an extract of mushrooms or sake lees that contain L-ergothioneine as the L-ergothioneine contained in the present improvement composition. However, commercially available L-ergothioneine that has been chemically synthesized may also be used.

Mushrooms from which L-ergothioneine can be extracted include Tamogitake (scientific name: Pleurotus cornucopiae var. citrinopileatus), Flammulina velutipes, etc., Leucopaxillus giganteus, etc., Phellinus linteus, etc., Tricholoma sp., etc., Tricholoma comatus, etc., Hericium yamabushitake, etc., Hericiaceae, etc. erinaceum, etc., Lyophyllum shimeji, etc., Lyophyllum decastes, etc., Rozites caperata, etc., Pholiota nameko, etc., Pleurotus pulmonarius, Pleurotus ostreatus, Pleurotus eryngii, etc., Mycoleptodonoides aitchisonii, etc., Agrocybe At least one or more may be selected from the group consisting of Grifola cylindracea, Grifola gargal, and others belonging to the Grifola genus. In particular, from the viewpoint of low side effects and safety when the extract is used for a long period of time, Tamogitake, Enokitake, Ginkgo biloba, Coprinus comatus, Yamabushitake, Honshimeji, Nameko, Pleurotus oyster, Pleurotus eryngii, and Bunaharitake are preferred, and Tamogitake is easy to collect domestically.

When the composition for improving the taste is made into a food composition (including beverages), in addition to L-ergothioneine, it may contain other ingredients commonly used in foods and beverages (nutritional ingredients such as vitamins and minerals, food ingredients, or food additives, etc.). Examples of other ingredients that can be used include ethanol or water as a solvent, sweeteners, flavorings, seasonings, coloring agents, preservatives, bulking agents, thickeners, thickening stabilizers, antioxidants, bittering agents, acidulants, emulsifiers, strengthening agents, manufacturing agents, excipients, disintegrants, binders, lubricants, coating agents, and plasticizers.

The food composition for improving cognitive function speed of this embodiment can be a solid, semi-solid or liquid food, and can be provided as, for example, confectionery (cookies, jellies, etc.), bread, processed fish products, processed livestock products, noodles, soups, sauces, side dishes, beverages (milk beverages, lactic acid bacteria beverages, soft drinks, vegetable beverages, powdered beverages, sports beverages, nutritional beverages, etc.). The food composition for improving cognitive function speed of this embodiment can be provided as health foods, functional foods, nutritional supplements, supplements, foods for specified health uses, foods for the sick, combination foods for the sick, or foods for the elderly. This improving composition can also be provided as a medicine or quasi-drug. In other words, it can be provided as a cognitive function speed improver.

The improvement composition can be in the form of a solid, liquid, powder, granule, paste, mousse, gel, jelly, tablet, or other form (dosage form). The improvement composition can also be in the form of a bag, container, capsule, or the like. In the case of a solid or tablet form, the amount of L-ergothioneine to be taken, as described below, can be contained in one piece. In the case of a liquid, powder, granule, paste, mousse, gel, or jelly form, the amount of L-ergothioneine to be taken, as described below, can be contained in one package.

The composition for improving the body's constitution can be used so that the intake of L-ergothioneine (intake per adult per day) is 1 mg to 30 mg, more preferably 3 mg to 25 mg, and even more preferably 5 mg to 25 mg. When L-ergothioneine is in a solidified or packaged form, the number of packages for daily intake can contain a total of 1 mg to 30 mg per adult per day. The intake of L-ergothioneine can be displayed on the package or the like as the recommended daily intake amount. The number of times per day to achieve the daily intake amount may be one or multiple times.

[Regarding the method for producing the composition for improving cognitive function speed]
The method for producing the present improvement composition (hereinafter, sometimes referred to as "the present production method") will be described.

In this production method, Tamogitake mushrooms are used as the raw material for L-ergothioneine. Tamogitake mushrooms used in this production method may be ones that grow naturally or ones that have been artificially cultivated. Tamogitake mushrooms may be used either raw or processed from harvested Tamogitake mushrooms. Tamogitake mushrooms that have been processed may be dried or powdered after drying. Mushrooms other than Tamogitake mushrooms may also be used as the raw material for L-ergothioneine.

The present manufacturing method involves an extract manufacturing step in which an aqueous solvent extract of Tamogitake (e.g. Tamogitake extract) is manufactured. The aqueous solvent extract of Tamogitake is a liquid (Tamogitake concentrate), semi-solid, or solid substance containing components extracted from Tamogitake by an aqueous solvent, or a mixture of one or more substances selected from these substances.

In the extract production process, for example, an aqueous solvent extract of Tamogitake can be produced according to a standard method. For example, Tamogitake is added to an aqueous solvent, crushed and stirred while heating, and then subjected to solid-liquid separation by filtration or the like to recover the liquid components, thereby producing an aqueous solvent extract of Tamogitake.

In the extract production process, after the liquid components described above are collected, ultrafiltration or ultrasonic treatment may be further performed. In this case, such ultrafiltration products (filtrate and residue) or ultrasonic treatment products become the aqueous solvent extract of Pleurotus cornucopiae finally obtained in this process.

Alternatively, the broth obtained by boiling Tamogitake mushrooms may be subjected to an ion exchange resin, and then an eluate of cationic compounds may be obtained from the ion exchange resin, concentrated, and the concentrated liquid may be passed through high performance liquid chromatography to separate and purify L-ergothioneine. In this case, the Tamogitake mushroom extract obtained by separation and purification is the aqueous solvent extract of Tamogitake mushroom finally obtained in this process.

The aqueous solvent used in the extract production process may be a solvent mainly composed of a polar solvent. The aqueous solvent may be one type of polar solvent or a mixture of two or more types of polar solvents. Examples of polar solvents that can be used in this production method include water, methanol, ethanol, acetic acid, formic acid, 1-butanol, 1-propanol, and 2-propanol. The preferred polar solvent is water.

The aqueous solvent may be used as it is without adding a solute to the polar solvent, or may be used after a solute has been mixed or dissolved in the polar solvent in advance. Examples of aqueous solvents with solutes mixed or dissolved include an aqueous citric acid solution obtained by mixing or dissolving citric acid in water, an aqueous sodium bicarbonate solution obtained by mixing or dissolving sodium bicarbonate in water, and a salt-acetic acid solution obtained by mixing or dissolving salt in acetic acid. The aqueous solvent may be acidic, neutral, or basic. The temperature of the aqueous solvent is not particularly limited as long as its function is not impaired, and may be low, normal, or high. Hot water can be used as a suitable aqueous solvent. The temperature of the hot water in the extract production process can be set to, for example, 90°C.

Regarding this production method, when the composition for improvement is a freeze-dried composition or a spray-dried composition, a drying step is carried out after the extract production step to produce a dried product (e.g., powder) of L-ergothioneine from an aqueous solvent extract of Tamogitake. The drying step can be performed using a freeze-drying method or a spray-drying method. When the freeze-drying method is used, for example, hot water is used as the aqueous solvent used in the extract production step to freeze-dry the hot water extract of Tamogitake (aqueous solvent extract of Tamogitake), thereby producing a dried product of L-ergothioneine. Note that when the composition for improvement is a composition consisting of Tamogitake extract, the drying step is not carried out. The composition for improvement can be a beverage consisting of an aqueous solvent extract of Tamogitake, or a beverage in which the aqueous solvent extract of Tamogitake is diluted.

Specifically, the drying process will be described in the case where a dried product of L-ergothioneine is produced from Pleurotus ulmoides extract using a freeze-drying method. In this case, the drying process includes a blending process in which dextrin is dissolved in Pleurotus ulmoides extract to prepare a material liquid, a preliminary freezing process in which the material liquid obtained in the blending process is frozen, and a freeze-drying process in which the material liquid after the preliminary process is freeze-dried under low-temperature and low-pressure conditions.

In the blending process, first, Tamogitake extract is added to the tank. Then, the Tamogitake extract in the tank is heated at a specified temperature while being stirred for a specified time. The Tamogitake extract is sterilized by heating. Next, a specified amount of dextrin is gradually added to the tank while adding water as needed. Once the addition is complete and it is confirmed that the dextrin has completely dissolved, the blending process ends. This results in a material liquid in which dextrin has been dissolved in Tamogitake extract.

For example, the stirring time (the above-mentioned specified time) of the Pleurotus cornucopiae extract can be 30 minutes, and the heating temperature (the above-mentioned specified temperature) can be 90° C. The amount of dextrin added, D (kg), can be calculated by the following formula 1. In formula 1, E represents the weight (kg) of the Pleurotus cornucopiae extract, Bx represents the Brix value (%) of the Pleurotus cornucopiae extract, and α represents a coefficient (e.g., 0.4).
Formula 1: D=E×Bx×α

For example, if 10 kg of Tamogitake extract with a Brix of 20% is added to a tank, the amount of dextrin added to the tank will be 0.8 kg. Tamogitake extract with a Brix of 20-25%, for example, can be used, and the dextrin can be Cluster Dextrin (registered trademark), a polymer with a cyclic structure within the molecule.

Next, in the preliminary freezing process, the liquid material obtained in the mixing process is divided into transparent bags (e.g. transparent bags with zippers) of, for example, 1 kg each, and the transparent bags are frozen in a freezer. The transparent bags are placed in the freezer on a metal tray such as aluminum. The temperature inside the freezer is set to, for example, -30°C. The freezing time is, for example, 18 to 42 hours. This causes the liquid material to freeze.

Next, in the freeze-drying process, the top of the transparent bag containing the liquid material frozen in the preliminary freezing process is cut off with a cutter or the like. The cut transparent bag is then placed in a low-temperature, low-pressure space (for example, inside a freeze-dryer). Inside the freeze-dryer, the shelf temperature is set to a low-temperature range (-25°C to -30°C) at the start. Inside the freeze-dryer, decompression begins from the start, and the shelf temperature is maintained in this low-temperature range until the internal pressure reaches a switching threshold (for example, 133 Pa). When the internal pressure reaches the switching threshold, the shelf temperature is set to 25°C and heating begins. When heating begins, the pressure inside the chamber is further reduced and the internal pressure is set to an extremely low-pressure range (for example, 20 Pa to 40 Pa), and the moisture in the frozen liquid material is evaporated and removed, and freeze-drying proceeds. The freeze-drying time is, for example, 40 to 50 hours. This allows a low-moisture solid to be obtained from the frozen liquid material.

After the freeze-drying process, the solid obtained by the freeze-drying process is crushed, and the crushed solid is passed through a sieve. For example, a sieve with a mesh size of 30 (nominal opening size of 600 μm) is used. This produces the present improvement composition in powder form.

In the extract production process or drying process, crushing, purification, concentration, drying, sterilization, etc. may be performed depending on the required purity and shape. Examples of the crushing method include crushing with a roll crusher, cutting with a food processor, grinding with a ball mill crusher, and crushing by impact with a hammer crusher. Examples of the purification method include filtration, distillation, recrystallization, reprecipitation, and methods using various types of chromatography. Examples of the concentration method include boiling concentration, vacuum concentration (reduced pressure concentration) using an evaporator, freeze concentration, and membrane concentration using a reverse osmosis membrane. Examples of the sterilization method include an autoclave, high frequency, and filter filtration.

Below, as an example of the present invention, a clinical trial on cognitive function using a food containing ergothioneine derived from Tamogitake mushroom is described for healthy subjects and subjects with mild cognitive impairment (MCI). Note that the present invention is not limited to this example as long as it does not exceed the gist of the invention. Furthermore, unless otherwise specified, the units and measurement methods described in this example are in accordance with JIS standards.

-Test method-
The clinical trial method used was a placebo-controlled randomized parallel group double-blind comparative study using two test food intake groups: an ergothioneine intake group (test food group) and a placebo intake group (control group). In the following, the ergothioneine intake group will be referred to as the "ergo group" and the placebo intake group as the "placebo group."

-Subject Allocation-
In selecting subjects, a screening survey was conducted on 70 individuals, and 52 individuals who met all of the eligibility criteria (1) to (11) and did not meet any of the exclusion criteria (A) to (D) were included as subjects.

<Eligibility Criteria>
(1) Those who have a score of 23 or more on the MMSE screening test. (2) Those aged 20 to 80 years. (3) Those with any gender. (4) Those who do not smoke. (5) Those who do not consume foods that are high in ergothioneine (foods that are high in ergothioneine: mushrooms, liver, grains, and beans).
(6) People who do not regularly use supplements or health foods. (7) People who do not suffer from lifestyle-related diseases (high blood pressure, diabetes, etc.), rheumatism, liver disorders, kidney disorders, or other chronic diseases. (8) People who have no history of treatment for malignant tumors, heart failure, or myocardial infarction. (9) People who have no history of allergies to mushrooms that contain large amounts of ergothioneine or medicines. (10) People who are not visiting hospitals or taking medication for the purpose of treatment. (11) People who have fully understood the contents of the clinical trial and have given written consent.

The Mini-Mental State Examination (MMSE) in eligibility criteria (1) is a test that evaluates the degree of progression of dementia by total score out of a maximum of 30 points, with a score of 20 or less being considered to indicate suspected dementia. In this study, subjects with an MMSE score of 23-27 points were deemed to have MCI, and subjects with a score of 28-30 points were deemed to be healthy.

<Exclusion Criteria>
(A) Pregnant or breastfeeding women, or those who intend to become pregnant during the study period. (B) Those who are participating in other clinical trials or clinical studies, or those who have participated in other clinical trials or clinical studies within the past three months. (C) Those who are unable to follow the instructions of the attending physician or medical institution staff. (D) Others who are judged by the study administrator to have some kind of problem.

The 52 subjects were randomly assigned to the ergometer group (26 subjects) and the placebo group (26 subjects) using the permuted block method to avoid bias in the MMSE scores due to subject background. The average MMSE scores were similar, 27.2 points for the ergometer group and 27.1 points for the placebo group.

In addition to the MMSE score, the subject background information was as follows: 11 men and 15 women in the erg group, and 7 men and 19 women in the placebo group. No significant differences were observed between groups in the subject background data for height, weight, BMI, systolic blood pressure, diastolic blood pressure, pulse rate, and body temperature.

- Inspection schedule and contents -
Each subject visited the medical institution (study implementation institution) according to the schedule shown in Table 1, and underwent the examinations, diagnoses, and tests listed in the examination items. For this schedule, starting from 0 weeks of intake (0w: date of first examination), examinations were performed at 4 weeks of intake (4w: within 28 days ± 3 days from the date of first examination), 8 weeks of intake (8w: within 56 days ± 6 days from the date of first examination), and 12 weeks of intake (12w: within 84 days ± 6 days from the date of first examination).

On each test day, after waking up, each subject had breakfast, and then underwent a medical interview, physical examination, blood pressure measurement, and blood test. The blood test measured the blood concentration of ergothioneine. After that, in accordance with the "Cognitrax Testing Guide," each subject underwent a Cognitrax test to measure cognitive function. In order to accurately measure cognitive function, each subject refrained from excessive eating and drinking on the day before each test.

The Cognitrax test is a cognitive function testing service designed for Japan by Health Solutions Co., Ltd., based on the cognitive function testing technology developed by CNS Vital Signs, Inc. in the United States. The Cognitrax test involves a verbal memory test, a visual memory test, a finger tapping test, a coding test (SDC test), a Stroop test, a sustained processing test, and a four-part sustained processing test, and the test results are converted into numerical values for each of 13 items (cognitive-related test items): overall memory, verbal memory, visual memory, cognitive function speed, reaction speed, overall attention, cognitive flexibility, processing speed, executive function, working memory, sustained attention, simple attention, and motor speed.

- Test food and method of taking the test food -
The test food for the ergo group was food containing 5 mg of ergothioneine obtained from Tamogitake mushroom extract (per 4 tablets), and for the placebo group, food containing 0 mg of ergothioneine (per 4 tablets). The test food for each group was packaged in an aluminum pouch and stored at room temperature. The test food was blinded and given to the subjects based on the identification number assigned to the food. All people involved in the study (subjects, interventionists, evaluators, etc.) were blinded, and the allocation list was not opened until the subjects to be analyzed were determined.

Starting the day after the first test, each subject was instructed to take two tablets with water at breakfast and two tablets with water at dinner (i.e., the daily intake of ergothioneine in the Ergo group was 5 mg). No specific dietary requirements were specified, and subjects were instructed to refrain from consuming large amounts of mushrooms during the intake period. If subjects forgot to take the tablet after breakfast, they were instructed to take it as soon as possible, and if they forgot to take the tablet after dinner, they were instructed to take it before going to bed. As a general rule, cases in which the food intake rate was 80% or more were treated as subjects for analysis.

The test foods used in the Ergo group were manufactured using a freeze-drying method. Specifically, the test foods used in the Ergo group were obtained by sequentially carrying out a blending process in which dextrin was dissolved in Pleurotus cornucopiae extract to prepare a material liquid, a preliminary freezing process in which the material liquid obtained in the blending process was frozen, and a freeze-drying process in which the material liquid after the preliminary process was freeze-dried under low-temperature, low-pressure conditions.

-Analysis method, analysis target-
Statistical methods used for comparison between groups were Student's t-test. Paired t-tests were used for intragroup comparisons with pre-ingestion values. The significance level was set at 5% on both sides. The actual measured values and changes in each data were used for analysis. StatMate V (Atoms Corporation) was used as statistical analysis software.

Of the 52 subjects, two were excluded from the analysis because they contracted influenza during the study and could not be tested during the designated test period, one had a food intake rate of 80% or more but was unable to consume food for two weeks, and one had a food intake rate of less than 80%. A statistical analysis (hereinafter referred to as "PPS case analysis") was performed on the Per Protocol Set (PPS) cases that met the study protocol. In addition, to confirm the effect of improving cognitive decline associated with aging, a statistical analysis (hereinafter referred to as "stratified analysis") was performed on specific age groups, including healthy subjects aged 40 years or older and subjects with MCI aged 30 years or older with an MMSE score of 27 points or less. Note that subjects in their 20s with an MMSE score of 27 points or less were excluded from the stratified analysis because it is difficult to determine whether they have a cognitive decline associated with aging.

The number of subjects in the PPS case analysis was 25 in the ergo group (1 excluded) and 23 in the placebo group (3 excluded). In terms of gender, there were 11 men and 14 women in the ergo group, and 5 men and 18 women in the placebo group. In terms of whether the subjects were healthy or had MCI, there were 14 healthy subjects and 11 MCI subjects in the ergo group, and 9 healthy subjects and 14 MCI subjects in the placebo group. In terms of the number of subjects in the stratified analysis, there were 20 in the ergo group and 19 in the placebo group. In terms of gender, there were 8 men and 12 women in the ergo group, and 3 men and 16 women in the placebo group. In terms of whether the subjects were healthy or had MCI, there were 10 healthy subjects and 10 MCI subjects in the ergo group, and 5 healthy subjects and 14 MCI subjects in the placebo group.

-Blood test results-
Table 2 shows the average change in ergothioneine blood concentration of subjects in the Ergo group and placebo group. According to Table 2, an increase in ergothioneine blood concentration due to ingestion of the test food was confirmed in the Ergo group. On the other hand, no increase in ergothioneine blood concentration due to ingestion of the test food was confirmed in the placebo group.

- Analysis results of the Cognitrax test -
1 to 13, for the 13 items in the Cognitrax test, the results of the PPS case analysis are shown with solid lines, the results of the stratified analysis are shown with wavy lines, the ergo group is shown with thick lines, and the placebo group is shown with thin lines. That is, the thick solid lines indicate "the results of the ergo group in the PPS case analysis", the thin solid lines indicate "the results of the placebo group in the PPS case analysis", the thick wavy lines indicate "the results of the ergo group in the stratified analysis", and the thin wavy lines indicate "the results of the placebo group in the stratified analysis". In the legends of each figure, the results of the PPS case analysis are represented as "PPS", and the results of the stratified analysis are represented as "stratified".

In each figure, the vertical axis represents the average change in score for the corresponding test item (change based on week 0 of intake) for the analysis subjects. The horizontal axis represents the timing of the test (week 0 of intake: 0w, week 4 of intake: 4w, week 8 of intake: 8w, week 12 of intake: 12w). Regarding the scores for each test item, for "reaction speed" and "overall attention", a smaller score (i.e., a larger decrease) indicates a better condition, while for the other items, a larger score (i.e., a larger increase) indicates a better condition.

Table 3 also shows the results of the significance test (p value) for the Ergo group from the results of the PPS case analysis. Table 4 also shows the detailed analysis results of the test items in which significant differences or significant trends between groups were confirmed from the results of the significance test shown in Table 3.

According to the results of the significance test in the PPS case analysis, a significant difference (p<0.05) was confirmed between the groups at 8 weeks for "cognitive function speed." In addition, a significant tendency (p<0.1) was confirmed between the groups at 12 weeks for "verbal memory," 12 weeks for "cognitive function speed," 12 weeks for "working memory," 4 weeks for "sustained attention," 4 weeks and 8 weeks for "simple attention," and 8 weeks and 12 weeks for "motor speed." Furthermore, there were no significant differences between the groups at 0 weeks of intake in any of the items. These results show that L-ergothioneine is effective in improving cognitive function speed, regardless of whether the subjects are healthy or have mild dementia.

Table 5 shows the results of the significance test (p value) for the Ergo group from the results of the stratified case analysis. Table 6 also shows the detailed analysis results of the test items in which significant differences or significant trends between groups were confirmed from the results of the significance tests shown in Table 5.

According to the results of the significance test in the stratified analysis, a significant difference (p<0.05) was confirmed between the groups for "verbal memory" at 12 weeks and for "simple attention" at 8 weeks. A significant tendency (p<0.1) was also confirmed between the groups for "cognitive function speed" at 8 weeks, for "sustained attention" at 4 weeks, and for "simple attention" at 4 weeks and 12 weeks. Although not shown in Table 6, a significant difference (p<0.05) was confirmed between the groups in the actual value at 4 weeks for "sustained attention." There was no significant difference between the groups at 0 weeks of intake in any of the items. These results show that L-ergothioneine is effective in improving verbal memory with aging, improving sustained attention with aging, and improving simple attention with aging.

From the above, it was found that L-ergothioneine is effective in improving cognitive function speed, verbal memory, and attention (sustained attention and simple attention (particularly the types of attention associated with aging)). The above-mentioned composition containing L-ergothioneine as an active ingredient can be used as a composition for improving verbal memory and attention (sustained attention and simple attention (particularly the types of attention associated with aging)) in addition to a composition for improving cognitive function speed.

The present invention is applicable to compositions used to improve cognitive function in the brain.

Claims (12)

A composition for improving cognitive function speed that contains L-ergothioneine as an active ingredient. The composition according to claim 1, wherein the L-ergothioneine is contained in an extract of Pleurotus cornucopiae. The composition according to claim 1 or 2, wherein the intake amount of L-ergothioneine is 1 mg to 30 mg per day for an adult. A composition for improving cognitive function speed that contains Tamogitake extract as an active ingredient. The composition according to any one of claims 1 to 4, which improves the information processing speed in the brain as the cognitive function speed. The composition according to any one of claims 1 to 5, which improves the cognitive function speed as well as the decline in verbal memory associated with aging. The composition according to any one of claims 1 to 6, which improves not only the cognitive function speed but also the decline in sustained attention associated with aging. The composition according to any one of claims 1 to 7, which improves not only the cognitive function speed but also the decline in simple attention associated with aging. The composition according to any one of claims 1 to 8, wherein the composition is a food composition. The composition according to claim 9, wherein the food composition is a health food, a functional food, a nutritional supplement, a supplement, a food for specified health uses, a food for the sick, or a food for the elderly. The composition according to any one of claims 1 to 8, wherein the composition is a pharmaceutical composition. The composition according to any one of claims 1 to 11, wherein the composition is a composition comprising Pleurotus cornucopiae extract, a freeze-dried composition, or a spray-dried composition.

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