Composition for improving working memory in cognitive functions

Abstract

To provide a novel composition for improving working memory in cognitive functions.SOLUTION: We have conducted intense study to discover a composition for improving working memory in cognitive functions, containing at least one of sulforaphane, glucoraphanin, sulforaphane and glucoraphanin as a contributing component. The composition containing at least one of sulforaphane, glucoraphanin, sulforaphane and glucoraphanin as a contributing component can be administered to or taken by a subject to improve the working memory.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving working memory in cognitive functions. [Background technology]

[0002] In Japan, with the aging society progressing, it is predicted that one in five people aged 65 or older will develop dementia by 2025, and one in four by 2036. Prevention is an urgent social issue, and there has been active research into effective methods for maintaining and improving cognitive function. Several reports have been published on the effects of sulforaphane on Alzheimer's dementia, which is said to account for more than half of all dementia cases. Non-Patent Document 1 discloses that in an Alzheimer's dementia model, ingestion of sulforaphane can protect the brain from amyloid beta damage and suppress cognitive dysfunction. Non-Patent Document 2 discloses that in an Alzheimer's dementia model, ingestion of sulforaphane improves learning behavior and increases the number of cholinergic neurons thought to control memory in the brain. Patent Document 1 discloses that sulforaphane has an inhibitory effect on tau protein aggregation and suggests that it may be useful in the treatment or prevention of neurodegenerative diseases such as Alzheimer's dementia. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2018-104414 [Non-patent literature]

[0004] [Non-Patent Document 1] Kim HPLCV et al., Amyloid, 20, 7-12 (2013). [Non-patent document 2] Zhang R et al., Int J Mol Sci., 8,14396-410 (2014). Summary of the Invention [Problem to be solved by the invention]

[0005] The problem to be solved by the present invention is to provide a novel composition for improving working memory in cognitive functions. [Means for solving the problem]

[0006] In light of the above, the present inventors have conducted extensive research and discovered a composition for improving working memory in cognitive function, which contains at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin as a contributing component. Specifically, administration or ingestion of a composition containing at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin as a contributing component can improve working memory. From this perspective, the present invention is defined as follows: The composition for improving working memory in cognitive function according to the present invention contains at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin as a contributing component. The composition for improving cognitive function according to the present invention contains a working memory-enhancing component, which is at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin. The working memory-enhancing component preferably improves age-related decline in working memory. The dementia-preventing composition according to the present invention contains a working memory-enhancing component, and the working memory-enhancing component is at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin. The composition for improving working memory in cognitive function according to the present invention contains, as a contributing component, at least one of a Brassicaceae plant, an extract or fraction thereof, and a pulverized product thereof. The composition for improving cognitive function according to the present invention contains a working memory-enhancing component, which is at least one of a Brassicaceae plant, an extract thereof, a fraction thereof, and a pulverized product thereof. The working memory-enhancing component preferably improves age-related decline in working memory. The dementia-preventing composition of the present invention contains a working memory-enhancing component, which is at least one of a Brassicaceae plant, an extract thereof or a fraction thereof, and a pulverized product thereof. In these embodiments, the Brassicaceae plant is preferably a broccoli sprout and / or a broccoli seed. [Effects of the Invention]

[0007] The present invention provides a novel composition for improving working memory in cognitive function. This composition improves cognitive function by improving working memory. Furthermore, the components of the composition, sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin, as well as the Brassicaceae plants containing these compounds, are all usable as food ingredients. Therefore, the composition for improving working memory in cognitive function of the present invention has fewer side effects and is safer than conventional pharmaceuticals containing non-natural compounds. DETAILED DESCRIPTION OF THE INVENTION

[0008] <Composition according to the present invention> The composition of the present invention is a composition for improving working memory in cognitive function, a composition for improving cognitive function, and a composition for preventing dementia, and contains at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin as a contributing component.

[0009] <Sulforaphane and glucoraphanin> Glucoraphanin is a type of glucosinolate and a precursor of sulforaphane. It is hydrolyzed by the enzyme myrosinase to form sulforaphane. Furthermore, when glucoraphanin is ingested by mammals such as humans, it is converted to sulforaphane by enzymes in intestinal bacteria and absorbed from the intestinal tract. Glucoraphanin is known to be abundant in Brassicaceae plants. In the present invention, glucoraphanin may be contained in a purified form in an agent or food composition, or in one or more forms selected from Brassicaceae plants, their extracts or fractions, and their pulverized products. The structural formulas of glucoraphanin and sulforaphane are shown below.

[0010] [ka]

[0011] [ka]

[0012] From the viewpoint of improving the efficiency of metabolism in the body, the composition of the present invention can further preferably contain myrosinase. The enzyme activity of myrosinase relative to the amount of glucoraphanin (myrosinase activity (UNIT) / glucoraphanin (mg)) may have a lower limit of 0.0001 (UNIT / mg) or more, preferably 0.001 (UNIT / mg) or more, and an upper limit of 0.022 (UNIT / mg) or less, preferably 0.01 (UNIT / mg) or less. Furthermore, myrosinase may be chemically synthesized or natural, and is not particularly limited, but natural myrosinase is preferred, and plant-derived myrosinase is more preferred. Examples of such plants include Brassicaceae plants, more specifically, mustard, Japanese radish, and wasabi. Myrosinase may be contained in an agent or food composition in a purified state, or in one or more forms selected from Brassicaceae plants, their extracts or fractions, and their pulverized products.

[0013] <Sulforaphen and glucoraphenin> Glucoraphenin is a type of glucosinolate and a precursor of sulforaphen. It is hydrolyzed by the enzyme myrosinase to become sulforaphen. Furthermore, when glucoraphenin is ingested by mammals such as humans, it is converted to sulforaphen by enzymes in intestinal bacteria and absorbed from the intestinal tract. Glucoraphenin is known to be contained in large amounts in Brassicaceae plants, particularly radishes and their leaves and seeds. In the present invention, glucoraphenin may be contained in an agent or food composition in a purified state, or in one or more forms selected from Brassicaceae plants, their extracts or fractions, and their pulverized products. The structural formulas of glucoraphenin and sulforaphene are respectively shown below.

[0014] [ka]

[0015] [ka]

[0016] Glucoraphenin is structurally similar to glucoraphanin, and therefore is expected to have similar actions and effects to glucoraphanin. For example, it has been reported that glucoraphenin contributes to the activity of phase II enzymes, which are indicators of the activation of the transcription factor Nrf2 (NF-E2-related-factor 2) (Barillari et al., J Agric Food Chem. 55(14), 5505-11, 2007.). In addition, Nrf2 is involved in the response to stress, such as oxidative stress. Itoh et al., Genes Dev. 1999 Jan 1;13(1), :76-86, 1999.), increases the gene expression of antioxidant enzymes (Ishii et al., J Biol Chem. 2000 May 26;275(21), :16023-9, 2000.), increases the gene expression of detoxification metabolic enzymes (Itoh et al., Biochem Biophys Res Commun. 1997 Jul 18;236(2), :313-22, 1997.), and reduces the gene expression of cytokines that cause inflammation (Kobayashi et al., Nat Commun. 2016 May 23;7, :11624, 2016. and Itoh et al., Mol Cell Biol. 2004 Jan;24(1), :36-45, 2016.). 2004.) and these effects are due to glucorafa Furthermore, it has been reported that activation of Nrf2 in the area of cognitive function suppresses oxidative stress and inflammation in the brain of Alzheimer's disease model mice, improving cognitive impairment (Uruno et al., Mol Cell Biol. 2020 Feb 27;40(6). pii , : e00467-19, 2020.) From the above, glucoraphenin is a compound of glucoraphanin and sucralose. It is presumed to have the same effect on cognitive function as ruforaphane.

[0017] The composition of the present invention can further preferably contain myrosinase from the viewpoint of improving the efficiency of metabolism in the body. The enzyme activity of myrosinase relative to the amount of glucoraphenin (myrosinase activity (unit) / glucoraphenin (mg)) may have a lower limit of 0.0001 (unit / mg) or more, preferably 0.001 (unit / mg) or more, and an upper limit of 0.022 (unit / mg) or less, preferably 0.01 (unit / mg) or less.

[0018] Furthermore, myrosinase may be chemically synthesized or natural, and is not particularly limited, but natural myrosinase is preferred, and plant-derived myrosinase is more preferred. Examples of such plants include Brassicaceae plants, more specifically, mustard, radish, wasabi, etc. Myrosinase may be contained in an agent or food composition in a purified state, or in one or more forms selected from Brassicaceae plants, their extracts or fractions, and their pulverized products.

[0019] <Brassicaceae plants> Brassicaceae plants are not particularly limited, but examples include broccoli, kale, cabbage, cauliflower, takana (leaf mustard greens), rapeseed, mustard greens, daikon radish, daikon radish leaves, nozawana (leaf mustard greens), komatsuna (Japanese mustard spinach), Chinese cabbage, Brussels sprouts, petit vert, snow radish, and plants produced by appropriate crossbreeding of these. The plant body part may be a plant growth body (buds, leaves, stems, roots, flowers, etc.), a sprout (germinated body), or a seed, and is not particularly limited. Among these, broccoli, which belongs to the genus Brassica of the Brassicaceae family, is more preferred. Furthermore, broccoli sprouts or seeds are particularly preferred due to their high content of sulforaphane and glucoraphanin. stomach.

[0020] <Broccoli sprout extract> When extracting at least one of sulforaphane and glucoraphanin from broccoli sprouts, any time after germination may be used as long as the sprouts are not yet matured, at which point the content per unit weight of sulforaphane and glucoraphanin decreases significantly. However, sprouts are preferably used 1 to 10 days, more preferably 1 to 3 days after germination. Broccoli sprouts with a sulforaphane and glucoraphanin content of 50 to 350 mg / 100 g (wet weight), more preferably 150 to 330 mg / 100 g (wet weight), and even more preferably 250 to 300 mg / 100 g (wet weight) are preferably used.

[0021] <Getting contributing components> At least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin can be obtained from Brassicaceae plants, including broccoli sprouts, by known methods. Isolated and purified sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin are commercially available, and these commercially available products can also be used. Examples of commercially available products include, but are not limited to, sulforaphane (Funakoshi Co., Ltd.) and L-Sulforaphene (Cayman Chemical Company).

[0022] <Extraction of glucoraphanin and glucoraphenin> For example, glucoraphanin and glucoraphenin can be obtained by extracting part or the whole plant, either as is or dried and crushed, with a solvent, etc. Examples of solvents include water, lower monohydric alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile, etc., and one or more of these can be used.

[0023] Considering that the composition of the present invention is orally administered or ingested, water, ethanol, or aqueous ethanol are particularly preferred as the extraction solvent. Examples of preferred extraction methods include extraction with hot water (90-100°C) for 10-50 minutes, or extraction with 0-100% aqueous ethanol by volume at room temperature or with heating for 1-10 days, and the resulting extract may be further fractionated and purified. Alternatively, glucoraphanin and glucoraphenin may be extracted by supercritical extraction.

[0024] <How to obtain sulforaphane from glucoraphanin> The method for obtaining sulforaphane from glucoraphanin is not limited, and it is sufficient to react glucoraphanin with myrosinase. For example, a Brassicaceae plant containing glucoraphanin can be crushed, ground, pulverized, sheared, squeezed, or the like without heating to cause the glucoraphanin to react with endogenous myrosinase and metabolize it to sulforaphane, or a method in which myrosinase is added to glucoraphanin to metabolize it to sulforaphane can be used. Sulforaphane can be obtained from a raw material containing sulforaphane metabolized from glucoraphanin by these methods using a method similar to that for glucoraphanin (for example, the extraction method described above).

[0025] <Method for obtaining sulforaphene from glucoraphenin> The method for obtaining sulforaphene from glucoraphenin is similar to the method for obtaining sulforaphane from glucoraphanin described above.

[0026] <Measurement of glucoraphanin and glucoraphenin concentrations> The concentration of glucoraphanin in the composition of the present invention can be measured by methods well known to those skilled in the art. For example, high performance liquid chromatography (HPLC) can be used, and a specific example of such a method is the method of Fahey et al. (Fahey et al., Proc. Natl. Acad. Sci. USA, 94, 10367-10372, 1997) etc. The concentration of glucoraphenin can be measured in the same manner as for glucoraphanin.

[0027] <Measurement of sulforaphane and sulforaphene concentrations> The concentrations of sulforaphane and sulforaphene in the composition can be measured by methods known to those skilled in the art, such as high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Specific examples of such methods include the method of Han et al. (Han et al., Int. J. Mol. Sci., 12, 1854-1861, 2011) and the method of Baenas et al. This can be done according to the method of Baenas et al. (Food Res. Int., 100(Pt1), 497-503, 2017.).

[0028] <Cognitive function> In the present invention, cognitive function refers to intellectual functions such as perception, attention, memory, reasoning, decision-making, and judgment. Furthermore, improving cognitive function refers to maintaining or improving cognitive function, and improving cognitive function refers to alleviating or curing various symptoms associated with cognitive decline. The cognitive function of the present invention includes at least working memory. The composition of the present invention is also useful for the prevention or treatment of diseases or conditions presenting with cognitive impairment for ameliorating or improving the condition. Examples of diseases or conditions presenting with cognitive impairment include dementia, non-dementia cognitive impairment, memory or learning disorders, etc. Dementia will be described later. An example of a non-dementia cognitive disorder is mild cognitive impairment (MCI), etc. An example of a memory or learning disorder is memory and learning disorders associated with brain development disorders, etc. Furthermore, the composition of the present invention is preferably used for age-related decline in cognitive function.

[0029] <Working memory> In the present invention, working memory in cognitive function refers to memory used when thinking about something, in other words, the ability to hold information in one's mind for a short period of time and process it simultaneously. The composition of the present invention can improve working memory in cognitive functions, preferably auditory working memory, more preferably digit span, and even more preferably reverse span. In cognitive function, improving working memory means maintaining or improving the function of working memory, and improving working memory means improving a declined working memory or preventing a decline in working memory. The composition of the present invention can be used in combination with other contributing ingredients to achieve a stronger working memory enhancing or working memory improving effect. Furthermore, it can be used in combination with working memory training, etc. Working memory training is training to remember certain information while performing another task. Examples include, but are not limited to, brain training games, N-Back tasks, double N-Back tasks, task switching, reading span tasks, operation span tasks, digit span, etc.

[0030] <Dementia prevention> Dementia in the present invention refers to a condition in which cognitive function is impaired due to the death or decline in activity of brain cells, making daily and social life difficult. The composition of the present invention is expected to have a preventive effect on dementia, particularly mild dementia. Dementia prevention refers to the prevention of the symptoms of dementia. Examples of dementia include senile dementia, Alzheimer's dementia, and cerebrovascular dementia. These include dementia caused by various diseases such as post-traumatic dementia, post-traumatic dementia, dementia caused by brain tumors, dementia caused by chronic subdural hematoma, dementia caused by normal pressure cerebral edema, post-meningitic dementia, and Parkinson's dementia.

[0031] <Form of composition> The compositions of the present invention can be administered as pharmaceuticals or ingested as food compositions. Specifically, they can be used as pharmaceuticals or food compositions for humans or animals, or as ingredients or preparations to be incorporated into such pharmaceuticals or food compositions. These food compositions include foods, functional foods, foods for specified health uses, foods for patients, and supplements that are based on the concept of preventing, ameliorating, or improving the decline in working memory or cognitive function, and are labeled as such as necessary. Examples of labeling methods include, but are not limited to, "maintenance of cognitive function," "improvement of cognitive function," "improvement of cognitive function," "maintenance of working memory in cognitive function," "improvement of working memory in cognitive function," "improvement of working memory in cognitive function," "maintenance of memory," "improvement of memory," "maintenance of recall," "maintenance of word recall," "maintenance of work efficiency," "improvement of work efficiency," "maintenance of calculation work efficiency," "improvement of calculation work efficiency," "maintenance of office work efficiency," and "improvement of office work efficiency." These indications may be attached to containers and packaging means in a known manner, or the above explanations may be displayed or distributed in advertisements, price lists or transaction documents relating to the product, or information containing these contents may be provided by electromagnetic means (such as the Internet).

[0032] <Agent> Preferred administration forms of the composition of the present invention as a pharmaceutical preparation include oral administration using tablets, coated tablets, capsules, granules, powders, solutions, syrups, emulsions, etc. However, parenteral administration forms are not excluded, and local tissue administration, subcutaneous, intradermal, intramuscular, or intravenous administration by injection, or intranasal administration by volatilizing the active ingredient, etc., may also be used. The composition may be formulated using known adjuvants commonly used in the pharmaceutical formulation technology field, such as excipients, binders, disintegrants, lubricants, colorants, flavorings, solubilizers, suspending agents, and coating agents. The composition may also be in the form of a pharmaceutical or quasi-drug.

[0033] <Food composition> Examples of forms in which the composition of the present invention can be ingested as a food composition include general foods such as fresh foods (raw vegetables), beverages (juice, coffee, black tea, green tea, carbonated drinks, sports drinks, green juice, etc.), sweets (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummy candy, candy tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, and other health foods (tablets, capsules, etc.), and nutritional supplements (supplements, nutritional drinks, etc.). Various ingredients can be blended depending on the type, and food additives such as glucose, fructose, sucrose, maltose, sorbitol, corn starch, dextrin, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, cellulose, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorings, flavorings, and preservatives can be used as desired.

[0034] <Contributing components> A contributing component is a substance that affects the physiological functions of the body. The contributing components in foods for specified health uses and foods with functional claims are called "contributing components" and "functional contributing components." In the case of pharmaceuticals and quasi-drugs, the so-called "active ingredients" are minutes".

[0035] <Content of contributing components> When the composition of the present invention is used as an agent, it is not particularly limited, but preferably contains at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin in a total amount of 0.03% by mass or more, more preferably 0.5% by mass or more, and particularly preferably 5% by mass or more. Furthermore, when the composition of the present invention is used as a food composition, it is not particularly limited, but preferably contains at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin in a total amount of 0.01% by mass or more, more preferably 0.04% by mass or more, and particularly preferably 0.25% by mass or more.

[0036] <Dosage / Intake> The dosage or intake of the composition of the present invention, when administered / ingested to a human subject, varies depending on the subject's sex, symptoms, age, and administration method. However, a daily dose of at least one of sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin is generally 24 mg or more for an adult (body weight approximately 60 kg), with 30 mg or more being preferred from the viewpoint of fully exerting the effect. This daily amount can be administered / ingested all at once or in several divided doses, and may be administered before, after, or between meals. Furthermore, the administration / ingestion period is not particularly limited, but continuous intake for 12 weeks or more is preferred. The aforementioned daily dosage / intake amount varies depending on the form of the composition, but refers to the recommended daily intake amount indicated, or the amount contained in one bottle in the case of a beverage that is usually consumed in one sitting. [Example]

[0037] Example 1 The study design was a randomized, placebo-controlled, double-blind, parallel-group comparative study. This study involved healthy men and women, who underwent cognitive function tests and questionnaire surveys before and after lifestyle intervention.

[0038] <Research subjects> The study subjects were 144 healthy, right-handed men and women (ages: 60-80) whose native language was Japanese who did not normally play video games and did not fall under any of the exclusion criteria listed below. Note that video games also include the use of computers and smartphones. <Exclusion items> (1) Those with a history of mental illness, diabetes, neurological disorders, or heart disease (2) People taking drugs that affect cognitive function (e.g., benzodiazepines, antidepressants, central nervous system drugs) (3) Those who score 26 or less on the Mini Mental State Examination (MMSE), a screening test for dementia. (4) Those who score 5 or more on the Geriatric Depression Scale (GDS), a test to measure the degree of depression. (5) Those who score 12 or less on the Frontal Assessment Battery at Bedside (FAB), a frontal lobe function test (6) People who may develop food allergies (especially broccoli, milk, eggs, wheat, buckwheat, peanuts, shrimp, and crab) (7) A person who has a drinking habit in which the average amount of alcohol consumed per day in a week exceeds 60g (equivalent to three medium-sized bottles of beer or three cups of sake) in terms of pure alcohol. (8) Those who are participating in other trials or have participated in other trials within two months prior to the start of this trial. Those who have committed crimes (9) Those who are unable to play the requested games, take nutritional intake, and complete the lifestyle intervention diary.

[0039] <Grouping> In this study, subjects were assigned to one of four lifestyle interventions (Table 1) using a stratified random method that took gender into account (36 subjects in each group, including 12 men and 24 women). Subjects were blinded to their assigned group. Subjects took either their assigned sulforaphane supplement ("Sulforaphane," Kagome Co., Ltd., containing 10 mg of glucoraphanin per capsule) or three placebo capsules daily and played a 15-minute game daily for 12 weeks. The placebo capsules replaced the glucoraphanin in the sulforaphane supplement with cornstarch and crystalline cellulose.

[0040] [Table 1]

[0041] <Game Contents> The following brain training games (Brain Training, Nintendo) and Tetris games (Tetris DS, Nintendo) and dedicated game consoles (Nintendo 3DS) were loaned to the research subjects and used in the test. <Brain Training: Reading and Calculation Games> For the research subjects in the cognitive intervention group, "brain training" was used. For "brain training," the following games (1) to (4) were played for approximately 15 minutes each day. Each game took approximately 30 seconds to 1 minute to complete. The number of games that could be played increased as the participants continued playing, but the subjects were asked to play games (1) and (2) every day and to play the other games evenly. (1) A calculation game in which you perform simple arithmetic operations as quickly as possible (2) A game in which you read aloud short passages such as waka poems or parts of novels as quickly as possible (3) A game in which you translate sentences that combine kanji and kana into kana and count the number of characters. (4) A game where you select numbers displayed on the screen in ascending order. (5) A game where you count the number of people displayed on the screen (6) A game in which you calculate according to the three numbers and two operation instructions displayed. (7) A game in which you compare the time on two clocks and calculate the time difference.

[0042] <Tetris: Puzzle Game> For the study subjects in the non-cognitive intervention group, Tetris was used to maintain the intervention schedule of playing games using new equipment. The study subjects were asked to play Tetris for about 15 minutes every day. Tetris is a game in which pieces of stone gradually fall from the top of the screen. This game involves stacking blocks by rotating them and moving them left and right. When a row is filled with no gaps, it disappears and you get a score. Furthermore, if you clear many rows at the same time, you can get a lot of points at once. The game ends when the rows reach the top of the game screen, but you can get a high score by manipulating the blocks to clear many rows without ending the game.

[0043] <Cognitive function test> A trained psychologist administered a standardized cognitive function test (WAIS-III) A cognitive function test for working memory was conducted using a portion of the Japanese Language and Linguistics Standards Act (JSLAS) published by Nippon Bunka Kagakusha. Working memory was measured using "backwards recitation (digit recitation)".

[0044] <Measurement of working memory (reverse recitation (digit recitation))> This test is included in the WAIS-III and requires participants to read numbers in reverse order as they are read aloud by an examiner. If the answer is correct, the examiner reads out a longer number and the participant repeats it in the same way. If the same digit is repeated incorrectly, the test is stopped. The longer the number of digits that can be said in reverse order, the higher the score. The maximum number of digits is 7. The change was calculated by subtracting the score before the intervention from the score after the intervention, and the mean ± standard deviation of the change is shown in Table 2.

[0045] <Measurements of other evaluation items> Other assessment items include processing speed (codes, symbols), reasoning, and the WAIS-III. Logical memory (immediate recall, delayed recall), attention (new Stroop test), and visuospatial ability (mental rotation test (MR)) were performed. Processing speed (code, symbol), logical memory (immediate recall, delayed recall), and the new Stroop test were performed according to the method of Nouchi et al. (Nouchi et al. Trials 13, 32, 2012.), and MR was performed according to the method of Peters et al. (Peters et al., Brain and Cognition 28, 39-58, 1995.).

[0046] <Analysis method> To analyze the effects of nutritional intervention, cognitive intervention, and their synergistic effects, the data of two study subjects who dropped out was imputed using the data of 142 subjects. Permutation ANCOVA analysis was performed on the data of 144 subjects to determine the effects of nutritional intervention or cognitive intervention for the groups with nutritional intervention (Example 1 and Example 2), without nutritional intervention (Comparative Example 1 and control), with cognitive intervention (Example 1 and Comparative Example 1), and without cognitive intervention (Example 2 and control). In the ANCOVA analysis, age and gender were adjusted for pre-intervention MMSE (general cognitive function) scores, and a p<0.05 was considered significant. The ANCOVA analysis was performed using the "aovp" function in the lmPerm package (http: / / cran.r-project.org / web / packages / lmPerm / index.html). Finally, the false discovery rate (FDR) correction method was used to adjust the p-values (Benjamini, Y. et al., J. Educational and Behavioral Statistics 25, 60-83. (2000)). All analyses were performed using software (R ver. 3.53).

[0047] The analysis results are shown in Table 2. The analysis targets for categories 1 to 3 are as follows: Category 1: Effects of nutritional intervention (with or without sulforaphane intake) Category 2: Effects of cognitive intervention (with or without brain training) Category 3: Synergistic effects of nutritional and cognitive interventions

[0048] <Result> The sulforaphane group showed significantly higher scores in reverse digit span (a measure of working memory) than the placebo group (Table 2, Category 1). This suggests that sulforaphane has the effect of improving working memory in cognitive function and ameliorating the decline in working memory associated with aging. It is believed that this compound has an effect of improving or preventing the disease. In addition, the sulforaphane group also had significantly higher processing speed (symbols) than the placebo group. Furthermore, although no significant differences were observed, the sulforaphane group (Comparative Example 1) had higher mean values for processing speed (symbols), logical memory (immediate recall, delayed recall), and visual-spatial ability (MR) than the placebo group (control) in the Tetris game.

[0049] [Table 2] [Industrial Applicability]

[0050] One area in which the present invention is useful is the health food business.

Claims

[Claim 1] A composition for improving working memory in cognitive function, comprising: A composition comprising at least one component selected from sulforaphane, glucoraphanin, sulforaphen, and glucoraphenin as a contributing component.

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