supporting activities of daily living

Abstract

The invention provides a method for supporting operable activities in daily life by providing a combination of (a) long chain polyunsaturated fatty acids - in particular DHA and / or EPA - with (b) a nucleoside or nucleotide - in particular uridine or an equivalent thereof. The operable activities include eating; walking; toileting; bathing; grooming; dressing; using a communication device; having a conversation; going to an appointment; using a household appliance; washing dishes; cooking or preparing a beverage; writing; reading; doing household chores independently; carrying or shopping.

Description

Technical Field

[0001] This invention relates to articles containing long-chain polyunsaturated fatty acids and / or nucleotides or their equivalents, and articles that support daily life activities. Background Technology

[0002] Neurological disorders or problems can be caused by aging and are commonly conditions affecting the brain, such as those associated with the formation of plaques or neurofibrillary tangles. In many cases, neurological disorders or problems can lead to loss of independence and require additional care or placement in nursing homes to ensure the individual can continue living.

[0003] WO02 / 088159 describes the neuroprotective effect of a lipoic acid derivative of uridine. WO2006 / 031683 relates to a method for improving cognitive and neurological function, as well as enhancing neurotransmitter synthesis and release and membrane synthesis in nerve and brain cells, the method comprising administering a composition containing guanosine. WO2007 / 004685 describes a composition containing DHA and arachidonic acid, the composition having activity in alleviating the decline in higher brain function caused by organ-related brain injury. WO2007 / 004689 discloses a composition having activity in alleviating reduced daily activity and / or depressive symptoms, the composition containing arachidonic acid and / or a compound having arachidonic acid as a fatty acid component. US2007 / 0004670 describes a method for improving memory, learning, cognition, synaptic transmission and neurotransmitter synthesis and release, as well as increasing phospholipid levels in subjects. WO2006 / 127620 discloses a composition containing DHA and UMP for treating subjects with memory impairment, learning problems or neurological disorders, such as patients with Alzheimer's disease.

[0004] Wurtman et al., Brain Research 2006, 1088(1), 83-92 discloses a composition of choline, UMP, and DHA that can increase the amount of synaptic proteins and phospholipids in the brain of gerbils and has the potential to be used to treat Alzheimer's disease. EP 1656839 discloses a composition for feeding infants whose mothers have metabolic disorders during pregnancy, the composition containing DHA, EPA, uridine, and choline. WO2007 / 058538 discloses a composition for treating various diseases such as AIDS, diarrhea, etc., wherein the composition contains a) DHA and EPA, b) uridine, and c) choline. EP 1666092 discloses a composition of DHA and uridine for treating Alzheimer's disease, depression, and / or diabetes. JP 3-576318B2 discloses a nutritional composition that promotes growth and maintains health, the composition containing DHA and UMP. WO 03 / 041701 discloses a composition containing DHA, EPA, choline, methionine, vitamin B6, folic acid, zinc, magnesium, and UMP with substituted nucleobases, for the treatment of Parkinson's disease, epilepsy, schizophrenia, paranoia, depression, sleep disorders, psychosis, dementia, ADHA, memory impairment, chronic fatigue syndrome, and movement disorders.

[0005] None of the aforementioned documents discloses improvements to daily living activities as defined in this invention. Furthermore, it should be understood that this invention is not related to the treatment of Alzheimer's disease or dementia itself, but rather to the treatment of patients and / or the elderly suffering from Alzheimer's disease or dementia. Summary of the Invention

[0006] The inventors have discovered that administering the compositions of the present invention can improve activities primarily involving (i) operational and executive brain functions (i.e., instrumental and / or basic activities of daily living). Such activities include a variety of activities that occur throughout the day, particularly housework, personal hygiene, and cooking. This discovery can particularly extend the independent lifestyle for people who have difficulty performing these activities (e.g., those with Alzheimer's disease, dementia, and / or older adults who are not demented or have dementia). Improvements in the ability to perform instrumental and / or basic activities of daily living are generally considered more important than improvements in memory and / or cognitive function.

[0007] This discovery is particularly unexpected because the coordination of these complex daily living activities is carried out by different parts of the brain: the operational aspects of these activities (primarily) are coordinated by the motor cortex, the executive aspects (e.g., scheduling) are coordinated by the prefrontal cortex, and memory functions are coordinated by the hippocampus and temporal cortex. Experimental results show that administering the composition of this invention to subjects with brain dysfunction (especially Alzheimer's disease) can restore these activities to near-normal levels. The inventors have therefore discovered that the composition of this invention has a significant stimulating effect on the instrumental and / or fundamental activities of daily living, particularly for individuals with Alzheimer's disease. The composition of this invention can support and enable these activities, which are primarily characterized by initiation, planning, and effective operational behaviors, to function.

[0008] In another aspect, the inventors have discovered that, in addition to the above, the compositions of the present invention for supporting said daily activities may advantageously contain folic acid, vitamin B12, and / or vitamin B6, preferably in relatively high doses. These vitamins have been found to be advantageously included in the present invention. It has been found that administering B vitamins can reduce physical activity during rest periods, thus ensuring good night's rest. Therefore, compositions of the present invention, if containing B vitamins, can advantageously support the daily activities of the present invention while providing good rest periods.

[0009] The discovery of this invention enables the resolution of a significant problem for people suffering from Alzheimer's disease, dementia, and / or aging (i.e., the elderly). Many participants dread the moment when they need to perform daily activities and become dependent on the help and support of others. Therefore, these participants particularly desire to extend their period of independence. The inventors of this invention have solved this problem by providing a (nutritional) composition that is easily ingested and enables the extension of relatively complex daily activities.

[0010] Specifically, this invention relates to improvements in independent activities, primarily in terms of operability. The invention particularly relates to improvements in the following independent activities: motor coordination—especially when eating or drinking; grasping objects; placing objects in the desired location; performing actions quickly; walking; maintaining body balance; washing clothes; cooking.

[0011] In another aspect of the invention, the invention relates to independent activities primarily involving operational aspects, among other higher brain functions. The invention particularly relates to improvements in independent activities such as: using communication devices—especially telephones; using household appliances—especially televisions; maintaining personal hygiene—especially trimming nails, combing hair, or shaving; dressing, cooking, shopping, and traveling.

[0012] It has been specifically found that administration of products containing DHA and uridine produces the desired improvements. Particularly advantageous is the co-administration of at least one of vitamin B6, vitamin B12, and / or folic acid with said DHA and / or uridine. The inclusion of these vitamins improves the efficacy of DHA and / or nucleotide administration. Further improvements can be achieved by co-administering phospholipids. While not wishing to be bound by theory, the inventors believe that phospholipids can enhance membrane function, further improving the effectiveness of the compositions of the present invention in supporting daily living activities.

[0013] Furthermore, the product of the present invention is preferably formulated such that it has a relatively low impact on appetite and other food consumption patterns, and is easy to consume. It is preferably free of herbal extracts, which may undergo quality changes and are difficult to include in stable sterile liquid products under normal conditions, and may contain components with known adverse biological functions. Detailed Implementation

[0014] This invention provides the use of a composition containing (a) DHA and / or EPA and (b) uridine or an equivalent thereof in the manufacture of a composition for supporting daily living activities. Alternatively, this invention provides a method for supporting daily living activities, the method comprising administering to a patient (particularly a patient with Alzheimer's disease) a composition containing (a) DHA and / or EPA and (b) uridine or an equivalent thereof.

[0015] In another aspect, the present invention provides a liquid composition containing, per 100 ml: 0.2-2 g uridine or uridine equivalent; 0.5-5 g DHA; 0.5-10 g protein; 2-20 g carbohydrates; 0.5-15 micrograms vitamin B12; 50-1000 micrograms folic acid and 0.1-10 mg vitamin B6, wherein the composition has a viscosity of 1-40 mPas at 20°C and a shear rate of 100 Hz; a weight molar osmotic pressure concentration of 300-800 mOsm / kg; and a calorific value of 0.2-3 kcal / ml.

[0016] LC-PUFA

[0017] This invention includes the use of at least one long-chain polyunsaturated fatty acid (LCP), preferably selected from docosahexaenoic acid (22:6ω-3; DHA), docosapentaenoic acid (22:5ω-3; DPA), and eicosapentaenoic acid (20:5ω-3; EPA). Preferably, the composition of this invention contains at least DHA, preferably DHA and EPA. More preferably, the composition contains DHA and at least one DHA precursor selected from EPA and DPA, and more preferably, the composition of this invention contains DHA, DPA, and EPA. The inventors recognize that only a portion of the DHA integrated in the brain comes from orally ingested DHA. A significant portion of the DHA integrated in the brain originates from the conversion of DPA to DHA in the brain. In another aspect, the composition of this invention preferably contains a significant amount of EPA. In the brain, EPA is converted to DPA(ω-3), increasing the subsequent conversion of DPA(ω-3) to DHA. Therefore, the composition of this invention preferably also contains a significant amount of EPA to further stimulate DHA formation in the body.

[0018] The provided LCP is preferably in the form of triglycerides, diglycerides, monoglycerides, free fatty acids or their salts or esters, phospholipids, lysophospholipids, glycerol ethers, lipoproteins, ceramides, glycolipids or combinations thereof. Preferably, the composition of the present invention contains at least DHA in the form of triglycerides.

[0019] The method of the present invention preferably includes administering 400-5000 mg (DHA+EPA) daily, more preferably 500-3000 mg daily. The proportion of (DHA+EPA) in the total fatty acids is preferably 5-50% by weight, more preferably 10-45% by weight, and most preferably 15-40% by weight. The method of the present invention preferably includes administering DHA, preferably in an amount of 300-4000 mg daily, more preferably 500-2500 mg daily. The method of the present invention preferably includes administering DHA, preferably a composition containing 300-4000 mg DHA per 100 ml, more preferably 500-2500 mg DHA per 100 ml. The composition of the present invention preferably contains 1-40% by weight of DHA based on total fatty acids, preferably 3-36% by weight of DHA based on total fatty acids, more preferably 10-30% by weight of DHA based on total fatty acids. The compositions of the present invention preferably contain 0.5-20% by weight of EPA based on total fatty acids, more preferably 2-10% by weight of EPA based on total fatty acids, and even more preferably 5-10% by weight of EPA based on total fatty acids. The weight ratio of DHA to the sum of EPA and DPA(ω-3) is preferably greater than 1.0, more preferably 1.2-10, and most preferably 2-8. The above proportions and amounts take into account and optimize several aspects, including palatability (too high LCP levels can reduce palatability and lead to decreased compliance), the balance between DHA and its precursors to ensure optimal efficacy related to the maximum dose, and the possibility of product formulations such as liquid, strips, or capsules.

[0020] The compositions of the present invention preferably contain very low amounts of arachidonic acid (AA; 20:4ω-6). Arachidonic acid is considered to counteract the effects of the compositions of the present invention. Subjects using the methods of the present invention normally ingest sufficient amounts of AA (precursors), and excessive daily doses may stimulate inflammatory responses and inhibit daily living activities. Preferably, the DHA / AA weight ratio in the compositions of the present invention is at least 5, preferably at least 10, more preferably at least 15, up to, for example, 60 or up to 30. The methods of the present invention preferably include administering a composition containing at least 5% by weight of arachidonic acid based on total fatty acids, more preferably less than 2.5% by weight, for example, down to 0.5% by weight. The ω-6 / ω-3 fatty acid (C 18 and higher) ratio in the products of the present invention is preferably less than 0.5, more preferably less than 0.2, for example, down to 0.05 or up to 0.1. The ω-6 / ω-3 fatty acid (C 20 and higher) ratio in the products of the present invention is preferably less than 0.3, more preferably less than 0.15, for example, down to 0.03 or up to 0.06.

[0021] The compositions of the present invention preferably comprise at least one oil selected from fish oil, algae oil, and lecithin. Preferably, the compositions of the present invention comprise fish oil containing DHA, EPA, and preferably DPA.

[0022] Saturated fatty acids and monounsaturated fatty acids

[0023] The compositions of the present invention preferably contain saturated fatty acids and / or monounsaturated fatty acids. The amount of saturated fatty acids is preferably 6-60% by weight, more preferably 12-40% by weight, and even more preferably 20-40% by weight, based on total fatty acids. Specifically, the amount of C14:O (myristic acid) + C16:O (palmitic acid) is preferably 5-50% by weight, more preferably 8-36% by weight, and even more preferably 15-30% by weight, based on total fatty acids. The total amount of monounsaturated fatty acids (e.g., oleic acid and palmitoleic acid) is preferably 5-40% by weight, and even more preferably 15-30% by weight. The presence of saturated fatty acids and / or monounsaturated fatty acids provides an energy source and improves daily life activities according to the present invention.

[0024] Phospholipids

[0025] Preferably, the composition of the present invention contains phospholipids, preferably 0.1-50% by weight of total lipids, more preferably 0.5-20% by weight, and even more preferably 1-5% by weight of total lipids. The total lipid content is preferably 10-30% by weight of dry matter, and / or 2-6g of lipids per 100ml of liquid composition. The presence of phospholipids can advantageously improve membrane function, thereby improving the function of different brain regions that play a (major) role in daily life activities. Moreover, phospholipids can improve the stability of the product of the present invention.

[0026] Folic acid, vitamin B12 and / or vitamin B6

[0027] The compositions of the present invention preferably—particularly in (relatively) high doses—contain folic acid, vitamin B12, and / or vitamin B6. The presence of these vitamins advantageously provides a combined effect of support and enabling daily living activities, while providing reduced physical activity during rest periods. Another advantage of simultaneously administering folic acid, vitamin B12, and / or vitamin B6 is that this can help patients deficient in these vitamins. Preferably, the compositions of the present invention contain at least two of folic acid, vitamin B12, and / or vitamin B6. More preferably, the compositions of the present invention contain folic acid, vitamin B12, and vitamin B6.

[0028] The compositions of the present invention preferably contain 50-1000 micrograms of folic acid per 100g of liquid product, more preferably 150-750 micrograms of folic acid per 100g of liquid product, and even more preferably 200-500 micrograms of folic acid per 100g of liquid product. The methods of the present invention preferably include administering 50-1000 micrograms of folic acid daily, more preferably 150-750 micrograms of folic acid daily, and even more preferably 200-500 micrograms of folic acid daily. The compositions of the present invention preferably contain 0.5-15 micrograms of vitamin B12 per 100g of liquid product, more preferably 1-10 micrograms of vitamin B12 per 100g of liquid product, and even more preferably 1.5-5 micrograms of vitamin B12 per 100g of liquid product. The methods of the present invention preferably include administering 0.5-15 micrograms of vitamin B12 daily, more preferably 1-10 micrograms of vitamin B12 daily, and even more preferably 1.5-5 micrograms of vitamin B12 daily. The composition of the present invention preferably comprises 0.1-10 mg of vitamin B6 per 100g of liquid product, more preferably 0.4-5 mg of vitamin B6 per 100g of liquid product, and even more preferably 0.6-5 mg of vitamin B6 per 100g of liquid product. The method of the present invention preferably comprises administering 0.1-10 micrograms of vitamin B6 daily, more preferably 0.5-5 mg of vitamin B6 daily, and even more preferably 0.75-5 mg of vitamin B6 daily.

[0029] Nucleotides

[0030] The compositions of the present invention preferably contain uridine and / or its equivalents, preferably selected from at least one uridine or its derivative selected from uridine (i.e., riboururacil), deoxyuridine (deoxyriboururacil), phosphate uridine (UMP, dUMP, UDP, UTP), nucleobase uridine, and acylated uridine. Preferably, the compositions of the present invention contain one or more phosphate uridines selected from uridine monophosphate (UMP), uridine diphosphate (UDP), and uridine triphosphate (UTP). Most preferably, the compositions of the present invention contain UMP, as UMP is most effectively absorbed by the body. Preferably, at least 50% by weight, more preferably at least 75% by weight, and most preferably at least 95% by weight of uridine in the compositions of the present invention are provided by UMP. The method of the present invention preferably comprises administering uridine (the cumulative amount of uridine, deoxyuridine, phosphate uridine, nucleobase uridine, and acylated uridine derivatives) at an amount of 0.08-3g per day, preferably 0.1-2g per day, and more preferably 0.2-1g per day.

[0031] Preferably, the compositions of the present invention contain uridine phosphate, more preferably uridine monophosphate (UMP). UMP is readily absorbed by the body. Therefore, the presence of UMP in the products of the present invention allows for high efficacy at the lowest possible dose and / or results in a smaller volume administered to the subject. The weight ratio of uridine to cytidine is preferably greater than 1.0, more preferably 2.0, and most preferably greater than 5.0. The term uridine as used herein refers to uridine and / or its equivalents. The term cytidine as used herein refers to cytidine and / or its equivalents. Although cytidine, which crosses the blood-brain barrier, is a precursor to uridine, the inclusion of uridine in the compositions of the present invention is more efficient and effective.

[0032] The method of the present invention preferably comprises administering uridine monophosphate (UMP) at an amount of 0.08-3 g per day, preferably 0.1-2 g per day, more preferably 0.2-1 g per day. The method of the present invention preferably comprises administering a composition containing 0.08-3 g UMP per 100 ml of liquid product, preferably 0.1-2 g UMP per 100 ml of liquid product, more preferably 0.2-1 g UMP per 100 ml of liquid product. Preferably, 1-37.5 mg UMP per kilogram of body weight per day is administered. The required dose of the equivalent substance, by weight, can be calculated from the dose of UMP by using the equimolar amounts of the molecular weight of the equivalent substance and the molecular weight of UMP (the latter being 324 Daltons). The amount of nucleotides or nucleosides and their derivatives is preferably 3-115 μmol per kg of body weight per day, preferably 5-35 μmol, or 0.25-9 mmol per day, preferably 0.3-6 mmol, most preferably 0.45-2.8 mmol.

[0033] Urate derivatives such as UDP, which are readily formed from dietary UMPs, appear to be important for the intracellular transport of glycoproteins and glycolipids, as well as their availability in the cytosol and plasma membrane.

[0034] In another preferred embodiment, the composition of the present invention preferably does not contain a large amount of other nucleotides. Therefore, the weight ratio of adenosine / uridine in the composition of the present invention is preferably less than 0.1, more preferably less than 0.01, and most preferably 0. The weight ratio of guanosine / uridine in the composition of the present invention is preferably less than 0.1, more preferably less than 0.01, and most preferably 0. The weight ratio of inosine / uridine in the composition of the present invention is preferably less than 0.1, more preferably less than 0.01, and most preferably 0.

[0035] Uric acid and LCP conjugate

[0036] The inventors have discovered that nucleotide equivalents, as defined, particularly uridine sources, as defined, are important for supporting and / or enhancing the effects of lipid moieties, as defined above, on daily living activities. The conjugates of the present invention—particularly conjugates of (i) uridine and (ii) DHA and / or EPA—have unexpected effects. This can be observed at the biochemical level by improving ceramide metabolism in the membrane, particularly by increasing glycolipids in the presence of impaired simple ceramides.

[0037] Methyl donor

[0038] Preferably, the compositions of the present invention contain a methyl donor. A methyl donor is a food-grade compound that can provide a methyl, methylene, or formyl group when administered to a human individual. The methyl donor contained in the compositions of the present invention is preferably selected from serine, methionine, choline, betaine, dimethylglycine, sarcosine, and their derivatives. Preferably, the compositions of the present invention contain choline and / or phosphatidylcholine. The method of the present invention preferably comprises administering more than 50 mg of choline daily, preferably 80-2000 mg of choline daily, more preferably 120-1000 mg of choline daily, and most preferably 150-600 mg of choline daily. The compositions of the present invention preferably contain 50 mg-3 g of choline per 100 ml of the liquid formulation of the present invention, preferably 200 mg-1000 mg of choline / 100 ml. Methyl donors (especially choline) are important meningeal precursors, thereby improving the function of brain regions involved in supporting daily living activities. In a specific preferred embodiment, the compositions of the present invention contain phospholipids and choline. It has been found that administering phospholipids along with choline can maintain high choline levels. Since choline is an important precursor to a neurotransmitter that affects muscles, high choline levels (produced by the administration of phospholipids) can support daily activities.

[0039] Minerals and trace elements

[0040] The compositions of the present invention can be further improved by containing one or more minerals. Preferably, the compositions of the present invention contain at least one mineral selected from zinc, magnesium, copper, manganese, and molybdenum. Preferably, the compositions of the present invention contain manganese and molybdenum.

[0041] manganese

[0042] Dietary manganese content is important for improving cell membrane function, particularly that of nerve cells. Individuals with nutritional deficiencies or a genetic or metabolic disorder involving impparted metabolic capacity for producing sphingomyelin and / or related compounds such as thioglycosides and glycosylated ceramides will particularly benefit from the presence of this mineral component. The daily amount of manganese administered is preferably more than 0.1 mg, more preferably 0.1-1 mg. Preferably, the method of the present invention comprises administering a (liquid) composition containing 0.05-2 mg of manganese per 100 ml, preferably 0.1-1 mg of manganese per 100 ml.

[0043] molybdenum

[0044] Additional molybdenum is highly preferred to enable the cofactor to function properly. Molybdenum appears to be important for the production of the correct membrane components (e.g., the thioglycoside components of the membrane) and, in particular, ensures the proper functioning of nerve cells. Moreover, the presence of appropriate amounts of molybdenum can delay brain atrophy in some elderly individuals during the aging process. The method of the present invention preferably comprises administering a composition containing 0.1-100 micrograms of molybdenum per 100 ml, preferably 1-50 μg of molybdenum per 100 ml.

[0045] Zinc

[0046] Adding zinc to products containing the aforementioned lipid or nucleotide fractions is preferred, as it helps stabilize proteins in the brain and prevents them from agglomerating. Zinc is essential for daily activities. The method of the present invention preferably comprises administering a composition containing 0.05 mg to 25 mg of zinc per 100 ml, preferably 0.1 to 10 mg of zinc per 100 ml.

[0047] selenium

[0048] The compositions of the present invention preferably contain selenium. The antioxidant activity of selenium can advantageously prevent and / or inhibit damage to brain regions that enable daily living activities. Lower selenium levels increase the risk of hospitalization, especially in older adults and patients with Alzheimer's disease. Preferably, the method of the present invention provides administration of a composition comprising 0.01-5 mg of selenium per 100 ml of liquid product, more preferably 0.02-0.1 mg of selenium per 100 ml of liquid product. The daily dose of selenium is preferably greater than 0.01 mg, more preferably 0.01-0.5 mg.

[0049] product

[0050] The compositions of the present invention are preferably ready-to-use liquid, solid, or semi-liquid products. They can also be concentrated forms suitable for dissolving or diluting or for fortifying a secondary product. The product can be a beverage, an emulsion, a dispersant, a pill or capsule, a strip, a granular or non-granular powder, a pudding, a flavoring agent, a gelling agent, an ice cream, a soup, a biscuit, a lollipop, a dessert, or other forms known in the art. The compositions of the present invention are preferably administered enterally, more preferably orally. Most preferably, they are administered via a straw.

[0051] Subjects who may benefit from the methods and compositions of the present invention (particularly patients with Alzheimer's disease, dementia, and / or the elderly) often experience eating-related problems. They have been given sensory abilities and / or muscle control, and in some cases, their desire to apply proper eating habits has been fulfilled. Swallowing and / or chewing are often problematic. Therefore, the present invention preferably has a low viscosity, preferably a measured viscosity of 1-2000 mPas at 20°C and a shear rate of 100 per second. More preferably, the compositions of the present invention are preferably provided in the form of a beverage that can be ingested through a straw, which makes the product easier to consume and improves compliance. In a preferred embodiment, the compositions of the present invention have a viscosity of 1-80 mPas at 20°C and a shear rate of 100 per second, more preferably 1-40 mPas at 20°C and a shear rate of 100 per second. For best patient acceptance, the compositions of the present invention preferably have a weight molar osmotic pressure concentration of 300-800 mOsm / kg.

[0052] In addition, many subjects (e.g., patients with Alzheimer's disease, dementia, and / or the elderly) experienced a general decrease in appetite and / or became malnourished. Therefore, it is advantageous to include other nutrients in the compositions of the present invention. However, the energy density of the product is preferably not high enough to interfere with normal eating habits. If in liquid form, the product of the present invention preferably contains 0.2-3 kcal / ml, more preferably 0.5-2 or 0.7-1.5 kcal / ml.

[0053] The compositions of the present invention preferably contain digestible carbohydrates. These digestible carbohydrates can positively influence the performance skills of subjects and have a beneficial effect superior to and exceeding that of compositions of the present invention containing LCP and / or uridine. The compositions of the present invention preferably comprise 1-50 grams of digestible carbohydrates per 100 ml of liquid product, more preferably 5-30 grams per 100 ml, and even more preferably 10-30 grams of carbohydrates per 100 ml. The total amount of digestible carbohydrates is preferably 25-80% by weight of dry matter, preferably 40-80% by weight of dry matter.

[0054] This product is primarily intended for frail elderly individuals, where muscle strength is preferentially improved. The compositions of this invention preferably contain protein to improve muscle strength. This improved muscle strength provides an important stimulus for supporting daily living activities and advantageously contributes to the method of this invention. The compositions of this invention preferably contain 0.5-15 grams of protein per 100 ml of liquid product, more preferably 1-10 grams per 100 ml of liquid product, and more preferably 1-5 grams per 100 ml of liquid product. Preferably, the compositions of this invention contain at least 80% by weight of milk-derived protein (e.g., whey and / or casein) based on total protein content.

[0055] The method of the present invention preferably includes administering a composition in 50-250 ml, more preferably 75-150 ml.

[0056] Subjects

[0057] The compositions of the present invention are preferably given to persons, more preferably (i) elderly persons (with or without dementia) and / or persons suffering from Alzheimer's disease, (senile) dementia, Parkinson's disease, multiple sclerosis, aphasia, apraxia, ataxia, dystonia, or motor disorders. In this regard, in the context of this application, elderly persons are considered to be 50 years of age or older, particularly 55 years of age or older, more particularly 60 years of age or older, and even more particularly 65 years of age or older. This rather broad definition takes into account the fact that average ages vary among different populations on different continents, etc. Most developed countries in the world have accepted the definition of "elderly" or "old" (as associated with the age at which retirement benefits begin) as 65 years of actual age, but like many Western concepts, this is not well-suited to situations such as those in Africa. Currently, there is no standard numerical guideline from the United Nations (UN), but the UN recognizes the use of a cutoff of 60 years or older to refer to the elderly population in Western countries. Depending on the environment, region, and country, a more traditional definition of elderly or "old" persons in Africa is associated with an actual age of 50-65 years.

[0058] The method of the present invention is particularly suitable for patients with Alzheimer's disease and / or MCI. Preferably, the composition of the present invention is given to subjects with Alzheimer's disease, more preferably subjects with early or mild Alzheimer's disease, and most preferably subjects with Alzheimer's disease, wherein the subjects have a Mini-Mental State Examination (MMSE) score of 16-27, preferably 20-26. The composition of the present invention has been found to be particularly effective in this subgroup of Alzheimer's patients. This group of patients is often on the verge of losing the ability to independently perform daily living activities. Therefore, restoring and improving the skills of this invention in this group of patients has particularly great benefit. For the same reasons given above, the method of the present invention is also suitable for older adults with and without dementia, especially older adults without dementia.

[0059] use

[0060] The method of the present invention is particularly intended to (i) support and / or enhance daily living activities and / or and / or prolong independent living.

[0061] The term "activities of daily living" as used in this invention refers to instrumental activities of daily living and / or basic activities of daily living. Specifically, this invention provides a method for supporting and / or enhancing instrumental activities of daily living and / or basic activities of daily living. Preferably, at least one of the following instrumental activities of daily living is supported and / or enhanced: performing light and / or heavy housework, cooking and / or preparing beverages, grocery shopping, using household appliances (especially the telephone), and taking medication. Preferably, at least one of the following basic activities of daily living is supported and / or enhanced: personal hygiene activities (especially washing and / or bathing), dressing, walking, and / or using the toilet.

[0062] The "prolonged independent living" used in this invention can be readily determined through trials that assess the impact of a treatment on the time before a patient enters a nursing home. The invention also relates to a method for increasing the time before admission to a nursing home, comprising administering the composition of this invention. Another benefit of this invention is reducing the burden on caregivers.

[0063] In one aspect, the present invention provides a method (or use) for the composition of the invention to improve the following abilities: (i) eating, walking, toileting, bathing, grooming, and / or dressing; and / or (ii) using communication devices (especially telephones), conversing, keeping appointments, using household appliances (especially televisions), washing dishes, cooking or preparing beverages, writing, reading, doing housework independently, carrying, and / or shopping. Generally, the method of the present invention is intended to support or improve the practical abilities described, which are more dependent on motor skills than cognitive abilities. Therefore, the method of the present invention can be used to improve quality of life.

[0064] Activities of daily living also include performing quick or safe movements, walking safely or without fear of falling, or maintaining balance under conditions that would be acceptable in young, healthy individuals. Supporting these activities in those who need such support can lead to the maintenance, restoration, or reduction of impaired abilities to walk safely outside, shop, go to the bathroom promptly, or climb stairs.

[0065] Other activities of daily living include sensorimotor skills, the proper presence of which is manifested in the ability to coordinate muscular or limb movements, particularly during eating or drinking, when grasping objects, or when wishing to place things in a precise place or specific location. Supporting these activities in those who require such support means maintaining, restoring, or reducing the rate of decline in the ability to cook, prepare beverages, eat, or drink.

[0066] Activities of daily living also include the ability to feel, report, touch, or clean all parts of the body. Supporting these activities in those who need it means restoring, maintaining, or reducing the reduction in the ability to touch or feel all parts of the body, to cleanse, and to maintain hygiene of one's own body and the human environment.

[0067] If these activities occur in normal daily life, supporting the person to a level that maintains their independence and / or allows them to live independently in society can be achieved by administering an effective amount of the composition of the present invention.

[0068] Improvements in daily living activities can be measured. Various tests can be used to measure daily living activities, including the Alzheimer's Disease Collaborative Research Activities of Daily Living Questionnaire (ADCS-ADL). This is a 23-item caregiver assessment questionnaire with possible scores ranging from 0 to 78, where 78 indicates full functional performance without impairment (see: Galasko, D; Bennett, D.; Sano, M.; Ernesto, C.; Thomas, R.; Grundman, M.; Ferris, S.; and the ADCS. 'An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimer's Disease. Alzheimer's Disease and Associated Disorders, 1997. Volume 11(2): S33-S39). These questions are specifically related to eating (1); walking (2); toileting (3); bathing (4); grooming (5); choosing and dressing (6); making phone calls (7); watching television (8); having conversations (9); clearing dishes from the table (10); finding personal items (11); getting or preparing drinks (12); cooking or making snacks (13); disposing of garbage or litter (14); traveling (15); shopping (16); going to appointments or meetings (17); being alone (18); discussing current events (19); reading (20); writing (21); entertainment, hobbies, or activities (22); and using household appliances (23). This trial was used in the clinical trial of Example 5.

[0069] In one embodiment, the present invention provides the compositions of the invention and a specification for administration of the compositions (preferably orally) and indicating that the products may be used for one or more of the following: (i) supporting daily living activities and / or prolonging independent living; (ii) stimulating eating, walking, toileting, bathing, grooming and / or dressing; or (iii) stimulating the use of communication devices (especially telephones), conversing, keeping appointments, using household appliances (especially televisions), washing dishes, cooking or preparing beverages, writing, reading, doing housework independently, carrying and / or shopping.

[0070] In another embodiment, the present invention provides the compositions of the invention and a specification for administration of the compositions (preferably orally) and for instructing the administration of the compositions of the invention to provide the health benefits described in published scientific papers, which describe positive results for one or more of the following: (i) support for daily living activities and / or prolongation of independent living; (ii) stimulation of eating, walking, toileting, bathing, grooming and / or dressing; or (iii) stimulation of using communication devices (especially telephones), engaging in conversation, keeping appointments, using household appliances (especially televisions), washing dishes, cooking or preparing beverages, writing, reading, doing housework independently, carrying and / or shopping.

[0071] Example

[0072] Example 1: In vivo study

[0073] A rat model of difficulty performing instrumental and / or basic daily living activities (ADLs) can be established by infusing β-amyloid protein, which produces neuropathic toxicity in the brain, into the lateral ventricles of the rats' brains. Rats infused in this manner showed impaired spontaneous activity in new environments, which is an important part of ADLs and corresponds to instrumental and / or basic ADLs in humans, particularly those with Alzheimer's disease. These infused rats explored new environments less extensively than control rats, as evidenced by reduced exploration time and shorter walking distances. This study used a dietary composition (Diet B) to overcome difficulties in ADLs.

[0074] Experimental Design

[0075] Four groups of rats received either β-amyloid protein (Abeta) or saline solution (Sham) infusion into the lateral ventricles. Five weeks prior to infusion, the rats were fed one of two diets—A or B. The four groups are summarized in Table 1. Table 2 lists the dietary compositions of the two diets. Diet A served as a control. Diet B was rich in, for example, DHA, uridine, and choline. These rats were placed in a new environment (a circular activity area with a diameter of 120 cm) for 15 minutes, and their gait patterns were analyzed.

[0076] Table 1: Rats with different infusion solutions and diets.

[0077]

[0078] Table 2: Components of the diet.

[0079]

[0080]

[0081] result

[0082] When fed the control diet (A), rats infused with abeta showed a shorter walking distance in the new environment. When fed the experimental diet (B), the rats infused with abeta returned to the level of exploration of the new environment as the control rats (Sham-operated rats, without abeta infusion). Figure 1 Rats infused with Abeta using diet A showed a reduction of approximately 25% in kinetic activity in the open field, but animals using diet B did not show a reduction.

[0083] Infusion of abeta into the lateral ventricle can lead to reduced activity. These effects were completely eliminated by feeding the therapeutic diet of the present invention. These beneficial effects indicate the benefits of using the compositions of the present invention in the methods of the present invention, particularly for improving instrumental activities of daily living and / or basic activities of daily living.

[0084] Example 2: Packaged composition

[0085] With The packaged composition contains, per 125 ml:

[0086] Energy 125kcal; Protein 3.9g; Carbohydrates 16.5g; Fat 4.9g.

[0087] The fat contains 1.5g DHA+EPA and 106mg phospholipids (soy lecithin); choline 400mg; UMP (uridine monophosphate) 625mg; vitamin E 40mg α-TE; vitamin C 80mg; selenium 60μg; vitamin B12 3μg; vitamin B6 1mg; folic acid 400μg.

[0088] Minerals and trace elements: Sodium 125mg; Potassium 187.5mg; Chlorine 156.3mg; Calcium 100mg; Phosphorus 87.5mg; Magnesium 25mg; Iron 2mg; Zinc 1.5mg; Copper 225μg; Manganese 0.41mg; Molybdenum 12.5μg; Chromium 8.4μg; Iodine 16.3μg. Vitamins: Vitamin A 200μg-RE; Vitamin D3 0.9μg; Vitamin K 6.6μg; Thiamine (B1) 0.19mg; Riboflavin (B2) 0.2mg; Niacin (B3) 2.25mg-NE; Pantothenic acid (B5) 0.66mg; Biotin 5μg.

[0089] The packaging indicates that the composition can improve daily living activities, particularly stimulating independent walking, bathing, grooming, dressing, using communication devices (especially telephones), using household appliances (especially televisions), washing dishes, cooking or preparing beverages, and / or writing. The composition is suitable for administration to patients with dementia or Alzheimer's disease.

[0090] Example 3: In vivo study

[0091] Rats were fed with specific B vitamins (vitamin B6, vitamin B12, vitamin B23, vitamin B12, vitamin B23, vitamin B12, vitamin B23, vitamin B12, vitamin B23, vitamin B12, vitamin B23, vitamin B24 ... 12 Rats were fed a diet rich in B vitamins (including folic acid) for 4 weeks. One group was fed a diet deficient in B vitamins, and another group was fed a diet rich in B vitamins. These rats were housed in captivity in four groups, and their locomotor activity was assessed in cages. The mean percentage change in activity between the 4-week intervention period and a control period was calculated.

[0092] During sleep (inactivity), the mean change in activity was decreased in rats fed a B-vitamin-rich diet compared to rats fed a B-vitamin-deficient diet (p = 0.046). In fact, compared to the control group, kinesthesia was increased in rats fed a B-vitamin-deficient diet and decreased in rats fed a B-vitamin-rich diet. Kinesthesia was reduced during sleep in rats fed a B-vitamin-deficient diet. Conversely, activity was reduced during sleep in rats fed a B-vitamin-rich diet. This suggests that rats exhibit a disrupted sleep pattern when induced to have B-vitamin deficiency. Therefore, health is affected by a B-vitamin-deficient diet because a disrupted sleep pattern is likely to impair health. Conversely, health was improved in rats fed a B-vitamin-rich diet: reduced kinesthesia led to increased rest time.

[0093] Example 5: Clinical Study

[0094] This study was conducted to evaluate the impact of a medical food intervention on daily living activities in participants with Alzheimer's disease (AD). Twenty-one participants were randomly assigned to a double-blind, 12-week study to receive once daily 125 ml (125 kcal) of a milk-based beverage containing either (a) the formula according to Example 2 (active product) or (b) an isoenergetic control beverage according to Example 2 (control product), but without EPA, DHA, phospholipids, choline, UMP, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6, and folic acid. Outcomes were measured using the ADCS-ADL questionnaire (Alzheimer's Disease Collaborative Research Activities of Daily Living).

[0095] Activities of daily living (ADL) were measured using the Alzheimer's Disease Collaborative Research Activities of Daily Living Questionnaire (ADCS-ADL). This is a 23-item caregiver assessment questionnaire with possible scores ranging from 0 to 78, where 78 indicates full functional performance without impairment. The ADCS-ADL assesses functional capacity across a wide severity range and is a fundamental tool used to collect ADL data for this study cohort.

[0096] result:

[0097] At baseline, there were no significant differences between the active product treatment group and the control product treatment group. However, after a 12-week intervention period, there was a significant difference in the increase in ADCS-ADL scores between the two groups (p = 0.024). The control group (n = 106) showed a mean increase of +0.72 points in ADCS-ADL scores, while the active product group (n = 106) showed a mean increase of +1.85 points. Figure 2 ).

[0098] After 12 weeks, the improvement in ADCS-ADL scores was mainly a result of improved instrumental activities.

[0099] This study demonstrates that 12 weeks of intervention with the active product of Example 2 can improve daily living activities.

Claims

1. A composition for supporting daily living activities, said composition comprising (a) DHA and / or EPA and (b) uridine or its equivalent.

2. The composition of claim 1, wherein the composition is administered to a subject who has difficulty performing the activities of daily living.

3. The composition of claim 1 or 2, wherein the activities of daily living are measured using the Alzheimer's Disease Collaborative Research Activities of Daily Living Questionnaire (ADCS-ADL).

4. The composition according to any one of claims 1-3, wherein the subject is a subject with Alzheimer's disease and a Mini-Mental State Examination (MMSE) score of 16-27.

5. The composition according to any one of claims 1-3, wherein the subject is an elderly person without dementia.

6. The composition according to any one of the preceding claims, wherein the composition further comprises folic acid, vitamin B12 and / or vitamin B6.

7. The composition according to any one of the preceding claims, wherein the activity comprises the ability to perform the following activities: (i) eating, walking, using the toilet, bathing, grooming, or dressing; or (ii) Using communication devices, having conversations, keeping appointments, using household appliances, washing dishes, cooking or preparing beverages, writing, reading, doing housework independently, moving or shopping.

8. The composition according to any one of the preceding claims, wherein each daily dose unit of the composition contains 0.1-2 g of uridine calculated in the form of uridine monophosphate.

9. The composition according to any one of the preceding claims, wherein each daily dose unit of the composition contains 300-3600 mg of DHA.

10. The composition according to any one of the preceding claims, wherein the weight ratio between the DHA and arachidonic acid is at least 2.

0.

11. The composition according to any one of the preceding claims, wherein the composition is a liquid, and the liquid has a measured viscosity of 1-40 mPas at 20°C and a shear rate of 100 per second.

12. The composition according to any one of the preceding claims, wherein each daily dose unit of the composition further contains 80-2000 mg of choline.

13. A composition for prolonging independent life, said composition comprising (a) DHA and / or EPA and (b) uridine or its equivalent.

14. A liquid composition, wherein each 100 ml of the liquid composition contains 0.2-2 g uridine or uridine equivalent; 0.5-5 g DHA; 0.5-10 g protein; 2-20 g carbohydrates; 0.5-15 micrograms vitamin B12; 50-1000 micrograms folic acid and 0.1-10 mg vitamin B6, wherein the composition has a viscosity of 1-40 mPas as determined at 20°C and a shear rate of 100 Hz; a weight molar osmotic pressure concentration of 300-800 mOsm / kg; and a calorific density of 0.2-3 kcal / ml.