U.S. patent application number 12/666611 was filed with the patent office on 2010-12-30 for memory in subjects with mini-mental state examination of 24-26.
This patent application is currently assigned to N.V. NUTRICIA. Invention is credited to Anke Bongers, Martine Groenendijk, Patrick Joseph Gerardus Hendrikus Kamphuis.
Application Number | 20100331258 12/666611 |
Document ID | / |
Family ID | 41580940 |
Filed Date | 2010-12-30 |
United States Patent
Application |
20100331258 |
Kind Code |
A1 |
Kamphuis; Patrick Joseph Gerardus
Hendrikus ; et al. |
December 30, 2010 |
MEMORY IN SUBJECTS WITH MINI-MENTAL STATE EXAMINATION OF 24-26
Abstract
The invention thus pertains to the use of a composition
comprising: (a) uridine or uridine phosphate; and (b)
docosahexaenoic acid and/or eicosapentaenoic acid, for improving
memory and/or the treatment or prevention of impaired memory
function, in a subject with a mini-mental state examination of
24-26, wherein said composition is enterally administered to the
subject. In the MMSE test, any score of 27 or higher (out of 30) is
effectively normal. In the patients with dementia, 20-26 indicates
mild dementia, 10-19 moderate dementia, and below 10 severe
dementia. It was the present inventors' belief that within the
group of 20-26, the memory impairment in the sub-group of 24-26 may
even be reversible, as the pathological pathways have just started
to develop. In this group of subjects the pathological pathways
have just started to develop. Clinical studies show excellent
results for this subgroup.
Inventors: |
Kamphuis; Patrick Joseph Gerardus
Hendrikus; (Utrecht, NL) ; Groenendijk; Martine;
(Barendrecht, NL) ; Bongers; Anke; (Veenendaal,
NL) |
Correspondence
Address: |
FOLEY AND LARDNER LLP;SUITE 500
3000 K STREET NW
WASHINGTON
DC
20007
US
|
Assignee: |
N.V. NUTRICIA
|
Family ID: |
41580940 |
Appl. No.: |
12/666611 |
Filed: |
June 20, 2008 |
PCT Filed: |
June 20, 2008 |
PCT NO: |
PCT/NL2008/050411 |
371 Date: |
May 11, 2010 |
Current U.S.
Class: |
514/17.5 ;
514/50; 514/51 |
Current CPC
Class: |
A23L 33/40 20160801;
A23V 2002/00 20130101; A61K 45/06 20130101; A61P 25/28 20180101;
A61K 31/7072 20130101; A61K 31/202 20130101; A61K 31/14 20130101;
A23L 33/10 20160801; A23L 33/12 20160801; A23L 33/16 20160801; A61K
31/557 20130101; A23L 33/15 20160801; A61K 31/14 20130101; A61K
2300/00 20130101; A61K 31/202 20130101; A61K 2300/00 20130101; A61K
31/557 20130101; A61K 2300/00 20130101; A61K 31/7072 20130101; A61K
2300/00 20130101; A23V 2002/00 20130101; A23V 2200/322 20130101;
A23V 2250/1868 20130101 |
Class at
Publication: |
514/17.5 ;
514/50; 514/51 |
International
Class: |
A61K 38/02 20060101
A61K038/02; A61K 31/7072 20060101 A61K031/7072; A61P 25/28 20060101
A61P025/28 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 26, 2007 |
NL |
PCT/NL2007/050306 |
Jun 26, 2007 |
NL |
PCT/NL2007/050307 |
Jun 27, 2007 |
NL |
PCT/NL2007/050310 |
Dec 20, 2007 |
EP |
07123811.7 |
Mar 4, 2008 |
NL |
PCT/NL2008/050124 |
Claims
1.-7. (canceled)
8. An enteral composition comprising: a. uridine or uridine
phosphate; and b. docosahexaenoic acid and/or eicosapentaenoic
acid.
9. The composition according to claim 8, further comprising
phospholipids, choline, vitamin E, vitamin C, selenium, vitamin
B12, vitamin B6 and folic acid.
10. The composition according to claim 8, comprising 0.1-2 g
uridine, calculated as uridine monophosphate, per daily dosage
unit.
11. The composition according to claim 8, comprising 400-5000 mg of
the sum of DHA and EPA per daily dosage unit.
12. The composition according to claim 10, comprising 400-5000 mg
of the sum of DHA and EPA per daily dosage unit.
13. The composition according to claim 8, comprising 1-50 gram
digestible carbohydrates per 100 ml.
14. The composition according to claim 8, comprising 0.5-10 g
protein per 100 ml.
15. The composition according to claim 8, comprising 0.2-3
kcal/ml.
16. The composition according to claim 8, comprising 1-50 gram
digestible carbohydrates per 100 ml, 0.5-10 g protein per 100 ml,
and 0.2-3 kcal/ml.
17. The composition according to claim 8, being a liquid product,
having a viscosity between 1 and 100 mPa.s as measured at a shear
rate of 100 s.sup.-1 at 20.degree. C.
18. A method for (i) improving delayed recall function and/or (ii)
the treatment and/or prevention of an impaired delayed recall
function of a subject, comprising enterally administering to the
subject a composition comprising: a. uridine or uridine phosphate;
and b. docosahexaenoic acid and/or eicosapentaenoic acid.
19. The method according to claim 18, wherein the subject has a
mini-mental state examination of 24-26.
20. The method according to claim 18, wherein the composition is
enterally administered to the subject at least one time per day for
a period of at least 3 weeks.
21. A method for improving memory and/or treatment or prevention of
impaired memory function in a subject with a mini-mental state
examination of 24 or 25, comprising enterally administering to the
subject a composition comprising: a. uridine or uridine phosphate;
and b. docosahexaenoic acid and/or eicosapentaenoic acid.
22. The method according to claim 21, wherein the composition is
enterally administered to the subject at least one time per day for
a period of at least 3 weeks.
Description
FIELD OF THE INVENTION
[0001] The invention relates to the use of a composition for
improving memory function, in a subject with a mini-mental state
examination of 24-26.
BACKGROUND OF THE INVENTION
[0002] Memory impairment is a serious shortcoming in many humans,
particularly those suffering from Alzheimer's disease and/or
elderly. Such impairments often have serious consequences, such as
reduced quality of life, difficulties in performing the activities
of daily living, potentially resulting in hospitalization or
institutionalization.
[0003] Several treatments have been suggested for the improvement
of memory function in subjects. However, very few have been proven
effective. Moreover, the administration of several nutritional
ingredients has also been suggested.
SUMMARY OF THE INVENTION
[0004] Nutritional therapy is particularly desired in subjects who
have relatively mild symptoms of memory impairment, i.e. subjects
with a mini-mental state examination score (MMSE) of 24 to 26. The
present inventors have recognized that in this particular subgroup
memory improvement has enormous effect for the subject activities
of daily living and quality of life. This subgroup of subjects is
distinct in that the pathological pathways have just started to
develop. In the MMSE test, any score of 27 or higher (out of 30) is
effectively normal. In the patients with dementia, 20-26 indicates
mild dementia, 10-19 moderate dementia, and below 10 severe
dementia. It was the present inventors' belief that within the
group of 20-26, the memory impairment in the sub-group of 24-26 may
even be reversible, as the pathological pathways have just started
to develop. It would be highly desired to improve the memory
function of this subgroup of subjects, as this may delay the need
or reduce the dosage of treatment with pharmaceutical drugs.
Moreover, improvements in subjects with a MMSE of 24 to 26 can
postpone the need for a subject to be hospitalized or
institutionalized, enable a longer independent living, improve the
quality of life or improve the ability to perform daily
activities.
[0005] The subgroup of subjects with a MMSE score of 24 to 26
comprises two populations. Firstly, it comprises those subjects who
do not receive medication for memory impairment, i.e. the drug
naive subjects. The treatment of this subgroup is particularly
preferred as in these subjects the balance between side effects and
benefits of pharmaceutical intervention is still negative.
Providing nutritional therapy to these subjects is desired because
of the relative lack of negative side effects. For subjects with a
MMSE of 24 to 26 who are drug naive, it is particularly important
to develop a therapy which delays the point in time where
pharmaceutical drugs have to be administered.
[0006] Secondly, the subgroup of subjects with a MMSE score of 24
to 26 comprises a population of subjects with a very mild form of
Alzheimer's Disease. Memory improvement through nutritional therapy
is particularly desired in subjects with a very mild form of
Alzheimer's Disease. If improvement of memory function could be
achieved pharmaceutical intervention could be reduced or even
postponed if significant improvements are observed.
[0007] It is however particularly difficult to find a (nutritional)
composition which effectively improves memory function in the group
with a MMSE of 24 to 26 as the pathological pathways have only
started to develop and symptoms are very mild. Detecting
differences between control and treatment group is particularly
difficult, and hence effective treatment requires intensive
testing.
[0008] The present inventors surprisingly found, through clinical
study, that administration of a composition containing (a) uridine
or uridine phosphate; and (b) docosahexaenoic acid and/or
eicosapentaenoic acid showed a significant improvement of memory
function in subjects with a MMSE of 24 to 26. Compliance and
tolerability were very high and side effects were relatively low.
It was particularly surprising that the present clinical data
showed an actual improvement in memory function, more than just a
reduction in the rate of decline in memory function. Additionally
it was found that in this subgroup the delayed recall function was
significantly improved. The results of the clinical study are
summarized in the examples.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The invention thus pertains to the use of a composition
comprising: [0010] a. uridine or uridine phosphate; and [0011] b.
docosahexaenoic acid and/or eicosapentaenoic acid for improving
memory and/or the treatment or prevention of impaired memory
function, in a subject with a mini-mental state examination of
24-26, wherein said composition is enterally administered to the
subject.
Subjects
[0012] The present invention relates to subjects with a mini-mental
state examination of 24, 25 or 26, i.e. of 24-26. The mini-mental
state examination (MMSE) is a brief 30-point questionnaire test
that is used to assess cognition. In the time span of about 10
minutes it samples various functions including memory and
orientation. The MMSE test includes simple questions and problems
in a number of areas: the time and place of the test, repeating
lists of words, language use and comprehension, and basic motor
skills. Any score of 27 or higher (out of 30) is effectively
normal; 20-26 indicates mild dementia; 10-19 moderate dementia, and
below 10 severe dementia. The MMSE is a standardized test.
Copyrights prevent the inventors from including a copy of the
questionnaire into the specification, but it is readily accessible
on the internet and available through copyright owner Psychological
Assessment Resources (PAR). It is first introduced by Folstein et
al. (Psych Res 12:189, 1975), and is widely used with small
modifications to assess cognition.
[0013] The subjects as treated in the present invention have a
mini-mental state examination score of 24-26 and are preferably
drug naive and/or suffer from a very mild form of Alzheimer's
disease, preferably drug naive subjects with a very mild
Alzheimer's disease and a MMSE of 24-26. The term "drug naive" as
used in the present invention refers to subjects who do not ingest
one or more of cholinesterase inhibitors, N-methyl-D-aspartate
(NMDA) antagonists and ginkgo biloba. In the clinical study
presented here, it was found that the present composition is
effective in drug naive subjects. The subject is preferably a
human, preferably an elderly human, preferably at least 50 years of
age.
Memory
[0014] The present invention relates to use of the present
composition for (i) the improvement of memory and/or (ii) treatment
and/or prevention of impaired memory function. Alternatively, the
present invention provides a method for (i) the improvement of
memory and/or (ii) treatment and/or prevention of impaired memory
function in a subject in need thereof, said method comprising the
administration of the present composition to said subject.
Particularly, the present invention relates to the treatment of an
impaired memory function. It was found that the memory function
actually improved when the present composition was administered to
the subject. The memory function of a human subject can suitably be
determined using the (modified) ADAS-cog, Wechsler Memory Scale,
WMS revised.
[0015] It was particularly found that in these subjects the delayed
recall function was improved. Delayed recall function can be
measured by a prose recall task 30-minute delay interval. Delayed
recall of a prose passage is not a measure to differentiate clearly
between very mild dementia of the Alzheimer type and normal ageing.
Hence, the present composition can also advantageously help
subjects not (yet) suffering from Alzheimer's disease in improving
the delayed recall function. Hence, in a preferred embodiment the
invention provides a method for improving delayed recall and/or the
treatment and/or prevention of an impaired delayed recall
function.
Uridine
[0016] Preferably the present composition comprises uridine and/or
uridine phosphate. Preferably the present composition comprises one
or more uridine phosphates selected from uridine monophosphate
(UMP), uridine diphosphate (UDP) and uridine triphosphate
(UTP).
[0017] Most preferably the present composition comprises UMP.
Preferably at least 50 wt. % of the uridine in the present
composition is provided by UMP, more preferably at least 75 wt. %,
most preferably at least 95 wt. %. The present method preferably
comprises the administration of uridine (the cumulative amount of
uridine, deoxyuridine, uridine phosphates, uracil and acylated
uridine derivatives) in 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 present
method preferably comprises the administration of a composition
comprising uridine in an amount of 0.08-3 g UMP per 100 ml liquid
product, preferably 0.1-2 g UMP per 100 ml liquid product, more
preferably 0.2-1 g per 100 ml liquid product. Preferably 1-37.5 mg
UMP per kilogram body weight is administered per day. The required
dosages of the equivalents on a weight base can be calculated from
the dose for UMP by taking equimolar amounts using the molecular
weight of the equivalent and of UMP, the latter being 324
Dalton.
Docosahexaenoic Acid and/or Eicosapentaenoic Acid
[0018] The present composition preferably comprises at least
docosahexaenoic acid (22:6 .omega.-3; DHA) and/or eicosapentaenoic
acid (20:5 .omega.-3; EPA), preferably DHA and EPA. The DHA and/or
EPA is preferably provided as triglycerides, diglycerides,
monoglycerides, free fatty acids or their salts or esters,
phospholipids, lysophospholipids, glycerol ethers, lipoproteins,
ceramides, glycolipids or combinations thereof. Preferably, the
present composition comprises at least DHA in triglyceride
form.
[0019] The present method preferably comprises the administration
of 400-5000 mg (DHA+EPA) per day, more preferably 500-3000 mg per
day, most preferably 1000-2500 mg per day. The proportion of
(DHA+EPA) of the total fatty acids present in the composition is
preferably 5-50 wt. %, more preferably 10-45 wt. %, most preferably
15-40 wt. %. The present method preferably comprises the
administration of DHA, preferably in an amount of 300-4000 mg per
day, more preferably 500-2500 mg per day.
[0020] The present composition preferably contains a very low
amount of arachidonic acid (AA). Preferably the weight ratio DHA/AA
in the present composition is at least 5, preferably at least 10,
more preferably at least 15, preferably up to e.g. 60 or up to 30.
The present method preferably comprises the administration of a
composition comprising less than 5 wt. % arachidonic acid based on
total fatty acids, more preferably below 2.5 wt. %, e.g. down to
0.5 wt %. The ratio omega-6/omega-3 fatty acids in the present
product is preferably below 0.5, more preferably below 0.2, e.g.
down to 0.05 or to 0.1. The ratio .omega.-6/.omega.-3 fatty acids
(C 20 and higher) in the present product is preferably below 0.3,
more preferably below 0.15, e.g. down to 0.03 or to 0.06.
[0021] An amount per day as described herein means an amount in a
daily dosage unit provided by the composition of the invention.
Such a daily dosage unit may be a single dosage, but it may also be
divided over two or three, or even more daily servings. If the
composition, as according to a preferred embodiment, is intended
for administration as a single unit, the amounts per day as
described herein, are preferably the amounts present in the
(preferably packaged) composition unit. Treatment preferably
involves administration once, twice or three times per day, more
preferably once per day for a period of at least 3 weeks.
[0022] The present composition preferably comprises 1-40 wt. % DHA
based on total fatty acids, preferably 3-36 wt. % DHA based on
total fatty acids, more preferably 10-30 wt. % DHA based on total
fatty acids. The present composition preferably comprises 0.5-20
wt. % EPA based on total fatty acids, preferably 2-10 wt. % EPA
based on total fatty acids, more preferably 5-10wt. % EPA based on
total fatty acids. The above-mentioned amounts take into account
and optimise several aspects, including taste (e.g. too high LCP
levels reduce taste, resulting in a reduced compliance).
[0023] The present composition preferably contains at least one oil
selected from fish oil, algae oil and eggs lipids. Preferably the
present composition contains fish oil comprising DHA and EPA.
Saturated and Monounsaturated Fatty Acids
[0024] The present composition preferably comprises saturated
and/or mono-unsaturated fatty acids. The amount of saturated fatty
acids is preferably 6-60 wt. % based on total fatty acids,
preferably 12-40 wt. %, more preferably 20-40 wt. % based on total
fatty acids. In particular the amount of C14:0 (myristic
acid)+C16:0 (palmitic acid) is preferably 5-50 wt. %, preferably
8-36, more preferably 15-30 wt. % wt. % based on total fatty acids.
The total amount of monounsaturated fatty acids, such as oleic acid
and palmitoleic acid, is preferably between 5 and 40 wt. %, more
preferably between 15 and 30 wt. %. A composition with these
preferred amounts was found to be very effective.
Phospholipids
[0025] Preferably, the present composition preferably comprises
phospholipids, preferably 0.1-50 wt. % phospholipids based on total
weight of lipids, more preferably 0.5-20 wt. %, more preferably
between 1 and 10% wt. %, most preferably between 1 and 5 wt. %
based on total weight of lipids. The total amount of lipids is
preferably between 10 and 30 wt. % on dry matter, and/or between 2
and 10 g lipid per 100 ml for a liquid composition. The composition
preferably comprises between 0.01 and 1 gram lecithin per 100 ml,
more preferably between 0.05 and 0.5 gram lecithin per 100 ml. A
composition with these preferred amounts was found to be very
effective.
Choline
[0026] Preferably the present composition contains choline and/or
phosphatidylcholine. The present method preferably comprises the
administration of more than 50 mg choline per day, preferably
80-2000 mg choline per day, more preferably 120-1000 mg choline per
day, most preferably 150-600 mg choline per day. The present
composition preferably comprises 50 mg to 3 gram choline per 100 ml
of the liquid formula, preferably 200 mg-1000 mg choline/100
ml.
Vitamins
[0027] The composition may advantageously contain vitamins,
preferably vitamin C, vitamin E and B vitamins, more preferably
vitamin C, vitamin E, vitamin B6, vitamin B12 and folic acid.
Advantageously, vitamin B12 and folate are included. The present
composition preferably comprises 50-1000 .mu.g folic acid, more
preferably 150-750 .mu.g, most preferably 200-500 .mu.g folic acid,
per 100 ml liquid product. The present method preferably comprises
the administration of 50-1000 .mu.g folic acid per day, more
preferably 150-750 .mu.g, most preferably 200-500 .mu.g folic acid
per day. The present composition preferably comprises 0.5-15 .mu.g
vitamin B12, more preferably 1-10 .mu.g, most preferably 1.5-5
.mu.g vitamin B12, per 100 ml liquid product. The present method
preferably comprises the administration 0.5-15 .mu.g vitamin B12
per day, more preferably 1-10 .mu.g, most preferably 1.5-5 .mu.g
vitamin B12 per day.
[0028] Preferably the present composition comprises one or more of
phospholipids, choline, vitamin E, vitamin C, selenium, vitamin
B12, vitamin B6 and folic acid, more preferably phospholipids,
choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6
and folic acid.
Product
[0029] The present composition is preferably a ready-to-use liquid,
solid, or semi-liquid product. The present composition is
preferably enterally administered, more preferably orally. Most
preferably the present composition is administered through a straw.
When it is a ready-to-use liquid, the daily liquid amount is
preferably between 75 and 200 ml per day or per unit, most
preferably between 90 and 150 ml/day.
[0030] The subjects that can benefit from the method and
composition of the invention often experience problems with eating.
Their sensory capabilities and/or control of muscles can become
imparted, as well as in some instances their ambition to apply
proper eating habits. Swallowing and/or mastication may be
problematic. Hence, the present composition is preferably provided
in the form of a drink capable of being ingested through a
straw.
[0031] The composition according to the invention preferably has a
low viscosity, preferably a viscosity between 1 and 2000 mPa.s
measured at a shear rate of 100 sec.sup.-1 at 20.degree. C., more
preferably a viscosity between 1 and 100 mPa.s measured at a shear
rate of 100 sec.sup.-1 at 20.degree. C. More preferably, the
present composition is provided in the form of a drink capable of
being ingested through a straw which makes the product even easier
to ingest and improves compliance. In a preferred embodiment the
present composition has a viscosity of 1-80 mPas at a shear rate of
100 per sec at 20.degree. C., more preferably of 1-40 mPas at a
shear rate of 100 per sec at 20.degree. C. These viscosity
measurements may for instance be performed using plate and cone
geometry.
[0032] To be optimally accepted by the subject, the present
composition preferably has an osmolality of 300 to 800 mOsm/kg.
However, the energy density of the product is preferably not so
high that it interferes with normal eating habits. When in liquid
form, the present product preferably contains between 0.2 and 3
kcal/ml, more preferably between 0.5 and 2, between 0.7 and 1.5
kcal/ml.
[0033] Advantageously the present composition contains digestible
carbohydrates. The present composition preferably contains between
1 and 50 gram digestible carbohydrates per 100 ml of a liquid
product, more preferably between 5 and 30 grams per 100 ml, more
preferably 10-30 grams carbohydrates per 100 ml. The total amount
of digestible carbohydrates is preferably between 25 and 80 wt. %
on dry matter, preferably 40-80 wt. % based on dry matter.
[0034] The present composition may further comprise protein,
preferably 0.5-10 g protein per 100 ml, more preferably 1-6 gram
protein per 100 ml, most preferably 2-6 gram protein/100 ml.
Preferably the present composition contain at least 80 wt. % milk
derived protein (e.g. whey and/or casein) based on total protein.
Proteins enable the manufacturing of palatable products, especially
for frail elderly.
EXAMPLES
Example 1
[0035] Packaged composition for the comprising per 125 ml:
[0036] Energy 125 kcal; Protein 3.9 g; Carbohydrate 16.5 g; Fat 4.9
g.
[0037] Fat includes 1.5 g DHA+EPA, and 106 mg phospholipids (soy
lecithin); Choline 400 mg; UMP (uridine monophosphate) 625 mg;
Vitamin E 40 mg .alpha.-TE; Vitamin C 80 mg; Selenium 60 .mu.g;
Vitamin B12 3 .mu.g; Vitamin B6 1 mg; Folic acid 400 .mu.g.
[0038] Minerals and trace elements: Sodium 125 mg; Potassium 187.5
mg; Chloride 156.3 mg; Calcium 100 mg; Phosphorus 87.5 mg;
Magnesium 25 mg; Iron 2 mg; Zinc 1.5 mg; Copper 225 .mu.g;
Manganese 0.41 mg; Molybdenum 12.5 .mu.g; Chromium 8.4 .mu.g;
Iodine 16.3 .mu.g. Vitamins: Vit. A 200 .mu.g-RE; vit. D3 0.9
.mu.g; vit. K 6.6 .mu.g; Thiamin (B1) 0.19 mg; Riboflavin (B2) 0.2
mg; Niacin (B3) 2.25 mg-NE; Pantothenic acid (B5) 0.66 mg; Biotin 5
.mu.g.
Example 2
Clinical study
[0039] Increasing evidence shows a role of nutrients in subjects
with impaired memory function. The present study was done to assess
the effect of an intervention with a medical food on memory in drug
naive, very mild Alzheimer's disease (AD) subjects. Drug naive very
mild AD subjects with a MMSE of 24-26 were randomly allocated in a
double-blind 12 weeks study to receive a 125 ml (125 kcal)
once-a-day milk-based drink with: (a) the formula according to
example 1 (active product) or (b) an iso-caloric control drink
according to example 1, but without EPA, DHA, phospholipids,
choline, UMP, vitamin E, vitamin C, selenium, vitamin B12, vitamin
B6 and folic acid (control product).
[0040] Outcome measure was a (delayed) verbal memory task (derived
from Wechsler Memory Scale-revised).
Results:
[0041] At baseline, there was no significant difference between the
group treated with the active product and the group treated with
the control product. However, there was a significant difference
between the two groups in the change in the delayed verbal memory
task (derived from Wechsler Memory scale-revised (WMS-r)) between
baseline and after 12 weeks of treatment. The group receiving
control product (n=66) had an average decline of -0.164 with a 95%
confidence interval including zero (-0.938 to 0.610) whereas the
group receiving active product (n=60) had an average improvement of
0.983 points on the delayed verbal memory scale derived from WMS-r
with a 95% confidence interval above zero (0.214 to 1.752).
[0042] This study demonstrates that intervention with the active
product for 12 weeks improves memory, particularly delayed recall
function in subjects with MMSE of 24-26 (see table 1).
TABLE-US-00001 TABLE 1 Delayed verbal memory score Group Subjects
with MMSE 24-26 (WMS-r) Control 66 -0.164 Treatment 60 +0.983
* * * * *