Composition for preventing deterioration in cognitive function and / or improving cognitive function

Abstract

To provide a novel composition for preventing the deterioration in a cognitive function or improving the cognitive function in a subject.SOLUTION: The present disclosure provides a composition for preventing the deterioration in a cognitive function and / or improving the cognitive function in a subject, the composition containing γ-aminobutyric acid. The composition prevents the deterioration in the cognitive function and / or improving it in the subject by increasing the level of insulin-like growth factor 1 in the blood. The content of the γ-aminobutyric acid is about 10-about 1000 mg.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to a composition for preventing and / or improving cognitive decline. [Background technology]

[0002] With the rapid aging of the population in recent years, the awareness of health among the elderly and the way in which they approach health are changing significantly. Specifically, in the past, attention was focused on extending healthy lifespan, and the health of the elderly was primarily focused on physical health, but in recent years, attention has been focused not only on physical health but also on brain health in order to live a comfortable life in retirement.

[0003] Among these, dementia and other disorders of cognitive function are attracting particular attention. Dementia can cause secondary problems such as wandering and traffic accidents, as well as problems for those around you, such as caregiver fatigue. In addition, the number of elderly people who suffer from forgetfulness due to aging and mild cognitive impairment (MCI), a condition in which cognitive function declines but does not interfere with daily life, is increasing, and it is said that about one in four elderly people fall into the pre-dementia stage. Mild cognitive impairment is said to be one step away from dementia, and if left untreated, the symptoms will worsen in the future and lead to dementia.

[0004] Most dementias are progressive diseases, and current medical treatments can only slow the progression of symptoms, but they cannot cure the disease completely. Therefore, early detection and diagnosis of dementia and halting its progression before it develops into dementia are extremely important measures. Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention has been made in consideration of these circumstances, and aims to provide a novel composition for suppressing or ameliorating the decline in cognitive function of a subject. [Means for solving the problem]

[0006] As a result of extensive research to solve the above problems, the inventors have confirmed that gamma-aminobutyric acid (GABA) has the effect of improving human cognitive function, and by conducting further research based on this finding, have completed the present invention.

[0007] Therefore, according to a main aspect of the present disclosure, the following invention is provided. (1) A composition for inhibiting and / or improving cognitive function decline in a subject, comprising gamma-aminobutyric acid. (2) The composition described in the above item, wherein the cognitive function includes logical thinking ability. (3) The composition of any one of the above items, wherein the cognitive function includes working memory. (4) The composition according to any one of the preceding items, wherein the cognitive function includes sustained attention. (5) The composition according to any one of the above items, wherein the logical thinking ability, the working memory ability, or the sustained attention ability is measured by Cognitrax. (6) The composition according to any one of the preceding items, wherein the cognitive function includes spatial cognition. (7) The composition of any one of the preceding items, wherein the cognitive function includes memory. (8) The composition according to any one of the above items, wherein the spatial cognition or memory is measured by the Urbans Neuropsychological Test. (9) The composition according to any one of the above items for improving the body's daily role functions. (10) The composition according to any one of the above items for improving vitality. (11) A composition according to any one of the above items for improving mental health. (12) The composition according to any one of the preceding items, wherein the physical role function, vitality, or mental health is measured by the SF-36. (13) The composition according to any one of the above items for inhibiting and / or improving cognitive function decline in a subject by increasing blood insulin-like growth factor 1 (IGF-1) concentration. (14) The composition according to any one of the preceding items, wherein the content of γ-aminobutyric acid is about 10 to about 1000 mg. (15) The composition according to any one of the preceding items, wherein the intake amount of the γ-aminobutyric acid is about 10 to about 1000 mg per day. (16) The composition according to any one of the preceding claims, taken daily for at least four weeks. (17) The composition according to any one of the preceding items, wherein the subject is a healthy individual. (18) The composition of any one of the preceding items, wherein the subject has a Mini-Mental State Examination (MMSE) score of 24 or more. (19) A composition according to any one of the preceding items, which is taken orally. (20) The composition according to any one of the above items, which is a food or drink, a food additive, a quasi-drug, or a pharmaceutical.

[0008] Furthermore, other features and notable actions and effects of the present disclosure besides those described above will become apparent to those skilled in the art by referring to the following description of the preferred embodiments of the present invention and the drawings. BEST MODE FOR CARRYING OUT THEINVENTION

[0009] Hereinafter, an embodiment and an example according to the present disclosure will be described with reference to the drawings. As described above, one embodiment of the present disclosure is a composition for inhibiting and / or improving cognitive function decline in a subject, comprising γ-aminobutyric acid.

[0010] In recent years, γ-aminobutyric acid (GABA, 4-aminobutyric acid) has been attracting attention as an amino acid that is widely distributed in nature and does not impair the taste of food when added to it. GABA is an inhibitory neurotransmitter that is abundant in the central nervous system of mammals, and is known to suppress excessive secretion of excitatory neurotransmitters, calm nerve excitement, and exert a relaxing effect and anti-stress effect. It is also known to have a wide range of physiological activities, such as lowering blood pressure, lowering cholesterol, relieving stress, reducing fatigue, improving sleep quality, and suppressing a decline in immunity. GABA is found in vegetables, grains, and the human body, making it easy to add to food, and GABA-containing chocolate and many supplements are on the market.

[0011] GABA is an amino acid that is widely distributed in nature, such as vegetables and grains, so in one embodiment of the present disclosure, GABA is not particularly limited in origin, as long as it can be used in food and beverages. For example, GABA-containing plant extracts or purified products may be used, or it may be prepared from a fermented product obtained by adding glutamic acid decarboxylase or a microorganism having the enzyme, such as lactic acid bacteria, to a raw material containing glutamic acid. GABA-containing products and commercially available GABA can also be used as raw materials for the composition of the present disclosure, as long as they do not impair the effects of the composition of the present disclosure.

[0012] In one embodiment of the present disclosure, the cognitive function of the subject can be measured by a cognitive function test or a neuropsychological test. The cognitive function test or the neuropsychological test may be either a question-based test or an observation-based test, and examples of the cognitive function test or the neuropsychological test include the Cognitrax test, the Urban Neuropsychological Test (RBANS), the Hasegawa Dementia Scale-Revised (HDS-R), the Mini-Cog, the MoCA, the Dementia Assessment Sheet in the Community Comprehensive Care System (DASC-21), the Mini-Mental State Examination (MMSE), the ABC Dementia Scale (ABC-DS), the Clock Drawing Test (CDT), the Frontal Assessment Battery (FAB), the Alzheimer's Disease Assessment Scale (ADAS), the Clinical Dementia Rating (CDR), and the Wechsler Adult Intelligence Scale. As long as it can grasp the function, it is not limited to these, but preferably the Cognitrax test and the Urbans neuropsychological test. Generally, cognitive function decline is easily regarded as memory decline, but the actual human cognitive function is made up of a complex relationship between various abilities such as memory, thinking, understanding, calculation, learning, language, and judgment. Therefore, when using a cognitive function test or a neuropsychological test to evaluate the effect of a test food on human cognitive function, it is preferable to be able to evaluate multiple areas or items of cognitive function.

[0013] The Cognitrax test is known as a test that can evaluate multiple areas or items of cognitive function. The Cognitrax test was developed by CNS Visual Signs, Inc. in the United States. It is a cognitive function testing service based on cognitive function testing technology and is conducted online. In the Cognitrax test, a test is conducted from a total of 10 types of tests, namely verbal memory test, visual memory test, finger tapping test, coding test (SDC test), Stroop test, attention shifting test, sustained processing test, facial expression recognition test, logical thinking test, and 4-part sustained processing test, depending on the purpose of the test, and the test results are quantified for a total of up to 16 items, including neurocognitive index, overall memory, verbal memory, visual memory, cognitive function speed, reaction time, overall attention, cognitive flexibility, processing speed, executive function, social cognition, logical thinking, working memory, sustained attention, simple attention, and motor speed.

[0014] The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is one of the neuropsychological tests standardized in the United States, and is a neuropsychological test task (test battery) that can be repeatedly evaluated in a short period of time (about 30 minutes). The RBANS can evaluate five cognitive domains: immediate memory, visuospatial / construction, language, attention, and delayed recall.

[0015] In one embodiment of the present disclosure, the cognitive functions whose decline is inhibited and / or improved by the composition of the present disclosure include logical thinking, working memory, sustained attention, spatial cognition, and memory, but are not particularly limited as long as they can be measured by the above-mentioned cognitive function test or neuropsychological test. Here, "logical thinking" refers to the ability to think logically based on so-called logic, and includes, for example, logical thinking evaluated by the Cognitrax test. "Working memory" refers to the ability to manipulate information while temporarily holding it, and includes, for example, working memory evaluated by the Cognitrax test. "Sustained attention" refers to the ability to sustain attention to things, and includes, for example, sustained attention evaluated by the Cognitrax test. "Spatial cognition" refers to the ability to quickly and accurately grasp and recognize the state and relationship of objects in three-dimensional space, such as the position, direction, posture, size, shape, and interval of the object, and includes, for example, visual-spatial and construction abilities evaluated by the Urbans neuropsychological test. "Memory" is the ability to remember things, including delayed recall as assessed by the Urbans Neuropsychological Test.

[0016] It is known that the decline of cognitive function evaluated by such cognitive function tests and neuropsychological tests leads to a decline in quality of life (QOL). For example, a decline in processing speed and executive function leads to difficulty in acting or dealing with things in an orderly manner, and a decline in sustained attention and simple attention leads to difficulty in concentrating on one thing or processing multiple things simultaneously. In one embodiment of the present disclosure, the composition of the present disclosure can improve such disadvantages in daily life by improving cognitive function.

[0017] The SF-36 is known as a method for assessing health-related QOL. The SF-36 (MOS 36-Item Short-Form Health Survey) is a self-report health status questionnaire that can assess and score eight health concepts (physical functioning, role functioning (physical), bodily pain, general health, vitality, social functioning, role functioning (mental), and mental health). High scores for each health concept (subscale) in the SF-36 are interpreted as follows:

[0018] Physical function: Ability to carry out all types of activity, including strenuous activities. Role-based functioning (physical): During the past month, there were no physical problems when performing work or usual activities. · Body pain: I have not had any body pain in the past month, and body pain has not interfered with my usual work in any way. · Overall health: My health is very good. Vitality: I was always full of vitality in the past month. Social functioning: During the past month, there were no physical or psychological reasons that interfered with your usual interactions with family, friends, neighbors, or other associates. Role functioning (mental): During the past month, there were no psychological problems when working or carrying out usual activities. Mental health: Over the past month, I have felt calm, happy, and at peace.

[0019] Although the biochemical mechanism of cognitive decline is still largely unknown, it is known that blood IGF-1 (insulin-like growth factor-1) level decreases with age. Therefore, it has been pointed out that a decrease in blood IGF-1 may cause neurodegeneration or cognitive decline. In one embodiment of the present disclosure, the composition of the present disclosure can be used to suppress cognitive decline and / or improve cognitive function by increasing blood IGF-1 concentration.

[0020] In one embodiment of the present disclosure, the content of GABA in the composition of the present disclosure is not particularly limited as long as the concentration or weight is such that the effect of the composition of the present disclosure can be obtained depending on the administration method, etc. The content of GABA in the composition of the present disclosure is preferably about 10 to about 1000 mg, and the lower limit of the content may be, for example, about 10 mg or more, about 30 mg or more, about 50 mg or more, about 70 mg or more, about 100 mg or more, about 150 mg or more, about 200 mg or more, about 300 mg or more, about 400 mg or more, about 500 mg or more, about 700 mg or more, and the upper limit of the content may be, for example, about 1000 mg or less, about 800 mg or less, about 700 mg or less, about 600 mg or less, about 500 mg or less, about 400 mg or less, about 300 mg or less, about 200 mg or less, about 100 mg or less, and the content may be any numerical range between these lower and upper limits.

[0021] In one embodiment of the present disclosure, the composition of the present disclosure may contain, in addition to GABA, any additive or any component that can be used in a composition that can be ingested into the body, depending on its form. Examples of these additives and components include, but are not limited to, vitamins including vitamin E and vitamin C, minerals, nutritional components, physiologically active components such as flavorings, excipients, binders, emulsifiers, tonicity agents (isotonicity agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, or coating agents that are mixed during formulation.

[0022] In one embodiment of the present disclosure, the form of the composition of the present disclosure is not particularly limited as long as it contains GABA, and it can be, for example, a pharmaceutical composition, a food or beverage (including functional foods such as foods for specified health uses, foods with nutritional value, and foods with functional claims, dietary supplements, health foods, and supplements), a food additive, a quasi-drug, or a medicine.

[0023] In one embodiment of the present disclosure, the composition of the present disclosure can be taken orally, and when used as an oral agent, its form can be, for example, a tablet (including a coated tablet), a capsule, a powder, a granule, a powder, a liquid, a suspension, an emulsion, a granule, a powder, a pill, a paste, a cream, a caplet, a gel, a chewable agent, a stick, etc. In addition, it can be used as a raw material for other pharmaceuticals after being adjusted into a form that is easily blended, such as a powder or granule form.

[0024] In one embodiment of the present disclosure, the composition of the present disclosure can be used for non-therapeutic purposes, and can be a non-therapeutic method of suppressing cognitive decline and / or improving cognitive function by ingesting the composition of the present disclosure. Such a method does not include a treatment or medical procedure, and the subject is not particularly limited, and is preferably a healthy individual, and more preferably the subject has a Mini-Mental State Examination (MMSE) score of 24 points or more. By having such a healthy individual ingest the composition of the present disclosure, it is possible to suppress cognitive decline and / or improve cognitive function. In addition, when used as a medicine or quasi-drug, it is also possible to claim efficacy such as suppressing cognitive decline and / or improving cognitive function. The MMSE is a test that evaluates the degree of progression of dementia, etc., based on a total score out of a maximum of 30 points, and dementia is suspected when the score is 23 points or less. Therefore, by targeting individuals who have an MMSE score of 24 or more and are aware of their declining cognitive function with the composition of the present disclosure, it may be possible to inhibit and / or improve the decline in cognitive function in individuals who have not yet developed dementia but who are becoming increasingly forgetful in their daily lives, or in individuals with mild cognitive impairment, who are considered to be at risk for dementia.

[0025] In one embodiment of the present disclosure, the daily intake of GABA contained in the composition of the present disclosure can be appropriately set depending on the form of the composition, the intake method, the purpose of use, and the age, weight, symptoms, etc. of the subject of intake. For example, from the viewpoint of more significantly exerting the effect of GABA contained in the composition of the present disclosure, it is preferable to take the daily intake of GABA contained in the composition of the present disclosure to be about 10 mg / day or more, more preferably about 25 mg / day or more, about 50 mg / day or more, about 60 mg / day or more, about 80 mg / day or more, about 100 mg / day or more, about 120 mg / day or more, about 150 mg / day or more, about 180 mg / day or more, about 200 mg / day or more, about 300 mg / day or more, about 400 mg / day or more, about 500 mg / day or more, about 800 mg / day or more, about 1000 mg / day or more. There is no particular upper limit to the daily intake amount of GABA contained in the composition of the present disclosure, so long as it is within the range in which the composition of the present disclosure can exert the effect of inhibiting and / or improving cognitive function decline.

[0026] In one embodiment of the present disclosure, the frequency of application of the method of the present disclosure or the frequency of ingestion of the composition of the present disclosure may be once or multiple times a day within a desired intake range, and the ingestion period may be appropriately set within a range in which the composition of the present disclosure can exert the effect of inhibiting and / or improving cognitive function decline.

[0027] As used herein, "about" means ±10% of the preceding numerical value.

[0028] (Example) The present disclosure will be described in more detail below using examples, but the present disclosure is not limited to these examples.

[0029] The experimental methods and materials used in the present disclosure are described below. Note that, although the following experimental methods are used in the present embodiment, similar results can be obtained by using other experimental methods.

[0030] In the following examples, a clinical trial was conducted on a test food containing GABA to confirm the effects of improving cognitive function and health-related QOL in humans who ingested the test food, and a test was also conducted on the IGF-1 blood concentration in humans who ingested the test food. Example 1

[0031] Two types of placebo-controlled randomized double-blind two-group parallel group comparative studies were conducted as clinical trials. The test foods were capsules containing 100 mg of GABA per capsule as the active food. The placebo foods (comparison foods) were capsules that did not contain GABA. Specifically, the placebo foods were capsules containing 100 mg of dextrin per capsule. In selecting subjects, a screening test was conducted to select people who met all of the eligibility criteria (1) to (5) and did not meet any of the exclusion criteria (1) to (7). Through screening tests, 60 subjects were selected for each study (120 in total). The MMSE (Mini-Mental State Examination) is a test that evaluates the degree of dementia progression based on a score out of 30 points, and a score of 23 or less is considered to indicate suspicion of dementia.

[0032] <Eligibility Criteria> (1) Japanese men and women aged 40 or older (2) People who are aware of their cognitive decline (3) Subjects who can take the test food every day for 12 weeks (4) Subjects with an MMSE score of 24 or more (5) Individuals who have been fully informed of the purpose and contents of the clinical trial, are capable of consenting, fully understand the purpose and contents of the clinical trial, voluntarily volunteer to participate in the clinical trial, and have given written consent to participate in the clinical trial.

[0033] <Exclusion criteria> (1) Persons who are undergoing any type of medication, outpatient treatment, or exercise or diet therapy under the supervision of a doctor (2) Those who are currently receiving treatment for mental disorders, sleep disorders, drug or alcohol dependence, etc., or who have a history of mental illness in the past. (3) Night shift or shift workers (4) Those with a current or past history of serious diseases such as diabetes, liver disease, kidney disease, or heart disease, or thyroid disease, adrenal gland disease, or other metabolic diseases. (5) People who use health foods, supplements, or medicines that affect cognitive function (6) Individuals who cannot comply with the management procedures during the clinical trial (7) Any other person who is deemed to have problems in carrying out the examination

[0034] A total of 120 subjects were randomly assigned to Study A active group, Study A placebo group, Study B active group, and Study B placebo group, 30 subjects each. Each subject in Study A active group received 2 tablets of the active food, each subject in Study A placebo group received 2 tablets of the placebo food, each subject in Study B active group received 1 tablet of the active food, and each subject in Study B placebo group received 1 tablet of the placebo food.

[0035] Each subject took one or two capsules of the assigned dose with water for 12 weeks, starting two weeks after the first screening test, according to the schedule shown in the table below. Each subject ate food freely during the intake period without any specific instructions. In Study A, all subjects in both the GABA group and the placebo group completed the study. On the other hand, in Study B, two subjects in the placebo group dropped out for personal reasons, and the final number of subjects analyzed was 30 in the GABA group and 28 in the placebo group. [Table 1]

[0036] To confirm the effects of improving cognitive function, the Cognitrax test and the Urbans neuropsychological test were conducted. As shown by ● in the test schedule in Table 1, the Cognitrax test was conducted five times in total: at screening, before starting the test food intake, 4 weeks after intake, 8 weeks after intake, and 12 weeks after intake. The Urbans neuropsychological test was conducted twice in total: before starting the test food intake and 12 weeks after intake.

[0037] In addition, the SF-36 was administered to assess health-related quality of life. The SF-36 was administered four times: before the start of intake of the test food, after 4 weeks, after 8 weeks, and after 12 weeks of intake.

[0038] (Cognitrax test) Tables 2 and 3 show the test results for the 16 areas that can be measured by the Cognitrax test. The results of Test A (200 mg of active food or placebo food) are shown in Table 2, and the results of Test B (100 mg of active food or placebo food) are shown in Table 3. The differences between the active food and placebo food groups in Test A and Test B are shown in Tables 4 and 5, respectively. [Table 2] JPEG2025069354000003.jpg105127 [Table 3] JPEG2025069354000005.jpg101127 [Table 4] [Table 5]

[0039] According to the results in Table 2, in Test A, after 8 weeks of intake, the GABA group showed a significant improvement in scores for working memory and sustained attention compared to the placebo group, and after 12 weeks of intake, the GABA group showed a significant improvement in scores for logical thinking compared to the placebo group. According to the results in Table 3, in Test B, after at least 8 weeks of intake, the GABA group showed a significant improvement in scores for motor speed compared to the placebo group. This shows that GABA is effective in improving logical thinking, working memory, sustained attention, and motor speed in healthy individuals.

[0040] Among them, the result that logical thinking improved was surprising, and in this technical field, logical thinking is not necessarily related to other brain functions, and it was not thought that improvement of other brain functions other than logical thinking would necessarily improve logical thinking. For example, it was thought that high concentrations of lutein or zeaxanthin in serum or the central nervous system were related to improvement of cognitive function in elderly people, but it has been reported that logical thinking measured by the CNS Fital Signs test method on which Cognitrax is based does not improve even if lutein or zeaxanthin is continuously taken for one year (Nutrients. 2017 Nov14;9(11)). In addition, although aerobic exercise is used as part of concussion rehabilitation, it has been reported that aerobic exercise does not improve logical thinking as measured by the CNS Fital Signs test method (JAthlTrain. 2018 Dec;53(12):1156-1165). Therefore, the fact that logical thinking improved along with other brain functions such as working memory and sustained attention through continuous intake of GABA overturns the conventional understanding.

[0041] (Urbans Neuropsychological Test) Tables 6 and 7 show the test results for the five areas that can be measured by the Urbans Neuropsychological Test. The results of Test A (200 mg of active food or placebo food) are shown in Table 6, and the results of Test B (100 mg of active food or placebo food) are shown in Table 7. The differences between the active food and placebo food groups in Test A and Test B are shown in Tables 8 and 9, respectively. [Table 6] [Table 7] [Table 8] [Table 9]

[0042] According to the results of Tables 6 and 7, after 12 weeks of intake in both Tests A and B, the GABA group showed a significant improvement in the scores for visuospatial and delayed recall compared to the placebo group. This shows that GABA is effective in improving visuospatial and delayed recall in healthy individuals.

[0043] (SF-36) Tables 10 and 11 show the test results for the eight areas that can be measured by the SF-36. The results of Test A (200 mg of active food or placebo food taken) are shown in Table 10, and the results of Test B (100 mg of active food or placebo food taken) are shown in Table 11. The differences between the active food and placebo food groups in Test A and Test B are shown in Tables 12 and 13, respectively. [Table 10] [Table 11] [Table 12] [Table 13]

[0044] According to the results of Table 11, in Test A, at least after 4 weeks of intake, the GABA group was able to confirm a significant improvement in vitality scores compared to the placebo group, and after 4 weeks of intake, the GABA group was able to confirm a significant improvement in mental health scores compared to the placebo group, and after 8 weeks of intake, the GABA group was able to confirm a significant improvement in daily role function (physical) scores compared to the placebo group. According to the results of Table 12, in Test B, after 8 weeks of intake, the GABA group was able to confirm a significant improvement in physical function scores compared to the placebo group. This shows that GABA is effective in improving daily role function (physical), vitality, mental health, and physical function in healthy individuals. Example 2

[0045] Of the 120 subjects in Example 1, 60 subjects who participated in Study A underwent blood tests six times in total: at screening, before starting intake of the test food, 4 weeks after intake, 8 weeks after intake, 12 weeks after intake, and 4 weeks after the end of intake, as indicated by ● in the test schedule in Table 1. The results are shown in Table 14. [Table 14]

[0046] As shown in Table 14, an increase in IGF-1 was observed in the group that took GABA. This shows that GABA increases IGF-1 in healthy individuals and contributes to improving cognitive function.

[0047] Needless to say, the present disclosure can be modified in various ways, is not limited to the embodiment described above, and can be modified in various ways without departing from the spirit and scope of the invention.

Claims

[Claim 1] The invention described in this specification.

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