WO2013177262A2

WO2013177262A2 - Methods for diagnosing cognitive impairment

Info

Publication number: WO2013177262A2
Application number: PCT/US2013/042193
Authority: WO
Inventors: Brian M. ZANGHI
Original assignee: Nestec SA
Current assignee: Nestec SA
Priority date: 2012-05-24
Filing date: 2013-05-22
Publication date: 2013-11-28
Anticipated expiration: 2014-11-24
Also published as: US20130317387A1; AR093752A1

Description

METHODS FOR DIAGNOSING COGNITIVE IMPAIRMENT

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application Serial No. 61 /651 182 .filed May 24, 2012, the disclosure of which is incorporated herein by this reference,

BACKGROU D OF THE I NVENTION

Field of the invention

{^'00021 The invention relates generally to methods for diagnosing cognitive impairment in canines and particularly to methods for diagnosing cognitive impairment in canines by measuring body temperature.

Description of Related Art

[00031 Aged, or aging canines frequently suffer some degree of cognitive impairment. Canine Cognitive Dysfunction Syndrome (CCDS) is the age related deterioration of cognitive abilities. Canines with CCDS exhibit various behavioral disorders. For example, they may not respond to their name or familiar commands, may get lost or confused even in familiar surroundings, may no longer greet or respond to their owners or visitors, may exhibit diminished daytime activity, may walk in circles, may shun affection, and may lose bladder or bowel control. Early detection of cognitive im airment will help healthcare professionals and pet owners make informed choices about reducing the risk of developing CDS in their canines. Nutritional supplementation has a potentially valuable role to play in maximizing the benefit of therapy in terms of increasing the canines' quality of life. Key to this benefit is the early detection of cognitive impairment thereby enabling canines to receive the most appropriate care.

[0004} Body temperatures cycle up and down throughout the day as part of the cireadian rhythm. Canines with cognitive impairment typically experience an alteration in their cireadian rhythms.

[0005} There remains a need for diagnosing cognitive impairment in canines to provide the most appropriate and effective level of treatment. The use of body temperature as an indicator of cognitive impairment provides a simple and convenient method lor veterinary clinicians and pet- owners. Such treatment will improve the canine's quality of life. The present invention satisfies this need.

SUMMARY OF THE INVENTIO [0006] It Is, therefore, an object of the present invention to provide methods for diagnosing cognitive impairment in canines.

|0007| This and other objects are achieved using methods for diagnosing cognitive impairment in a canine that involve measuring a fi st body temperature of the canine from about 0.5 to about 3 hours after waking; measuring a second body temperature of the canine from about 8 to about. 33 hours after measuring the first body temperature; and determining that the canine is cognitive!. impaired if the first body temperature is less than 0.6^oC lower than the second body temperature.

[0008] Other and further objects, features, and advantages of the present invention will be readily apparent to those skilled in the art

DETAILED DESCRIPTION OF THE INVEN ION

Definitions:

|0009j The term ^'"canine"^' means any canine susceptible to or suffering from cognitive impairment.

[001.0} The term "dog^"' means all domesticated canines, including working dogs and pet dogs. |0 t I) The term "senior" means a canine of an age having an increased risk for age-related disease, e.g., cognitive impairment, but may or may not. have obvious physical or behavioral characteristics of aging. For example, for dogs, "senior" means an age of from about 7 years to about 1 1 years, or older,

j0012{ The term "comparable control canine" means a canine of the same species and type or an individual canine evaluated at two different times.

|^'00!3) The term "diagnosing" means determining if a canine is suffering from or predicting If the canine is likely to developing cognitive impairment.

[0014] As used herein, ranges are used herein in shorthand, so as to avoid having to list and describe each and every value within, the range. Any appropriate value within die range can be selected, where appropriate, as the upper value, lower value, or the terminus f the range.

[0015) As used herein, the singular form of a word includes the plural, and vice versa, unless the context clearly dictates otherwise. Thus, the references "a", "an", and "the" are generally inclusive of the plurals of the respective terms. For example, reference to "a method" includes a plurality of such "methods," Similarly, the words "comprise" "comprises", and "comprising" are to be interpreted inclusively rather than exclusively. Likewise the terms "include". "including" and "or^" should all be construed io be inclusive, unless such a construction is clearly prohibited from the context,

10016 i The methods and compositions and other advances disclosed here are not limited to particular methodology, protocols, and reagents described herein because, as the skilled artisan will appreciate, they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to, and does not, limit the scope of that which is disclosed or claimed.

{^'00.1.7] Unless defined otherwise, all technical and scientific terms, terms of art, and acronyms used herein have the meanings commonly understood by one of ordinary skill in the art in the field(s) of the invention, or in the fieid(s) where the term is used.

{001 Sj All patents, patent applications, publications, technical and/or scholarly articles, and other references cited or referred to herein are in their entirety incorporated herein by reference to the extent allowed by law. The discussion of those references is intended merely to summarize the assertions made therein. ^" o admission is made that, any such patents, patent applications, publications or references, or any portion thereof, are relevant, material, or prior art The right to challenge the accuracy and pertinence of any assertion of such patents, patent applications, publications, and other references as relevant, material, or prior art is specifically reserved.

The Invention

J_.00I9J in one aspect the invention provides methods for diagnosing cognitive impairment in a canine. The methods comprise measuring a first body temperature of the canine from about 0.5 to about 3 hours after waking; measuring a second body temperature of the canine from about 8 to about 13 hours after measuring the first body temperature; and determining that the canine is cogmtively impaired if the first body temperature is less than 0.6°C lower than the second body temperature.

(0020] In one embodiment, both the first temperature and the second temperature are less than 38°C.

(00211 In various embodiments, the first body temperature of the canine is measured from 0.5 to about 3 hour after waking; preferably from about 1 to about 2.5 hours after waking; more preferably from about 1 to about 2 hours after waking.

[ 022| in various embodiments, the second body temperature is measured at about 8 to about 13 hours after measuring the first bod temperature, preferably from about 9 to about 12 hours after measuring the first body temperature, more preferably from about 9 to about 1 1 hours after measuring the first body temperature,

(0023 J in another aspect, the invention provides methods for diagnosing cognitive impairment i - canine. The methods comprising measuring a first body temperature of the canine at about 6 am to about 1.1 am; measuring a second body temperature of the canine at about 4 pm to about. 1 1 pm; and determining that the canine is eogmtively impaired if the first body temperature is less than 0.6°C lower than the second body temperature.

(0024] In one embodiment, both the first temperature and the second temperature are less than

38°C.

|0 25] in various embodiments, the first body temperature of the canine is measured, at about 6 am to about 1 1 am. preferably at about 7 am to 10 am, more preferably at about 8 am to 10 am. {0026 J In another embodiment, the second body temperature is measured at about 4 pm to about 1 1 pm, preferably at about 5 pm to about 11 pm, more preferably at about 6 pm to about. 8 pm. hi one embodiment, the second body temperature is measured at about 7 pm.

(0027| In various embodiments, the canine is a dog. In one embodiment, the dog is a senior dog. in another embodiment, the senior dog is 9 or more years of age,

(0028] The. inventions are based upon the discovery that body temperature in cognitive!y impaired eanin.es is lower compared to body temperature in comparable control canines that are not cognitive))' impaired. In addition, it was discovered that the range of daily body temperature in cogmiively impaired canines is lower compared to comparable control canines that are not cognitive!}¹ impaired. The invention allows veterinary and other clinicians to use body temperature to determine whether the canine is likely to develop cognitive impairment or is suffering from cognitive impairment and whether there is a need for further diagnostics or treatments. Having established the need for further diagnostics or treatments using the simple method for the invention, the cost and. risk of such further more expensive or invasive diagnostics or treatments are justified.

EXAMPLES

(0029] The invention can be further illustrated by the following examples, although it will be understood that these examples are included merely for purposes of illustration and are not. intended to limit the scope of the invention unless otherwise specifically indicated. Example 1

003ft] Sixty (60) dogs ere selected from a pool of seventy dogs, which were at least eight years of age. The selection was based on memory performance using a variable dela non- matching to position task (varDNMP). First, the dogs were placed in three non-overlapping groups that were defined as:

Group A: High Performing Memory (HPM), N^::: 12

Group B: Low Performing Memory (LPM). N^";24

Group C: Moderate Performing Memory (MPM), N^:::24

[0031 ] DNMP testing was carried out at. baseline and again after 45 days. Dogs were tested on three-choice varDNMP for 10 baseline days, and for 14 days during retest Ail DNMP testing will consist of variable-delayed testing in which delays of 20 and 90 seconds will occur with equal frequency over the 12 test trials per day, resulting in 60 trials for each delay during baseline and 84 trials for each delay during retest. The delays will occur randomly within the test sessions, with the constraint that, each delay will occur on exactly 6 trials.

[0032] Core body temperature was measured based on rectal temperature collected during the baseline phase and end-of-study phase. Core body temperature readings were recorded at 8AM (± 30rains), 10 AM (± 30mins k 1 PM (± 30mins), 3 PM {± 30mins). 7PM (± SOmms). and 1 :30 AM (± I Smms ).

(0033] To establish whether the varDNMP baseline groupings had different core body temperatures_., the control canines from each of the three groups were compared during the baseline portion of the study. As detailed in Table 1, the LPM canines had mean core (rectal) body temperature readings thai were quantitatively lower at all 6 time points recorded within a 24 hour period compared to the HPM and MPM canines. Of particular importance was the 7 pm recording, which demonstrated the peak body temperature. LPM dogs had a 0.44"C lower body temperature at this peak time compared to HPM and MPM canines. Referring to Table 1 , the data shows that body temperature can be used to diagnose cognitive impairment, in canines.

Table !

Body Temperature Data of Control Dogs (N-36) Recorded at Multiple Times

During the Day of the Baseline Phase

8:00 AM 10:00 AM 1 :00 PM 3:00 PM 7:00 PM 1 :30 AM

[003 j In the specification, there have been disclosed typical preferred embodiments of the invention. Although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation. The scope of the invention is set forth in the claims. Obviously many modifications and variations of the invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.

Claims

CLAIMS What is claimed is:

1 . A method for diagnosing cognitive impairment in a canine comprising

a. measuring a first body temperature of the canine from about. 0.5 to about 3 hours after waking:

b. measuring a second body temperature of the canine from about 8 to about 13 hours after measuring the first, body tempera lure; and

c. determining that the canine is cognitively impaired if the first, body temperature is less than 0.6°C lower than the second body temperature.

2. The method of claim 1 wherein the first body temperature of the canine is measured from about 1 to about 2.5 hours after waking.

3. The method, of claim 1 wherein the first body temperature of the canine is measured from about 1 to about 2 hours after waking.

4. The method of claim 1 wherein the second body temperature of the canine is measured from about 9 to about 12 hours after measuring the first body temperature.

5. The method of claim. 1 wherein the second body temperature of the canine is measured from about 9 to about J 1 hours after measuring the first body temperature.

6. The method of claim 1 wherein the canine is a dog.

7. The method of claim 6 wherein the dog is a senior dog.

8. The method of claim 7 wherein the senior dog is 9 or more years of age.

9. The method of claim 1 wherein both the first temperature and the second temperature are less than ?>8^''<.\

10. A method for diagnosing cognitive impairment in a canine comprising

a. measuring a first body temperature of the canine at about 6 am to about 11 am;

b, .measuring a second body temperature of the canine at. about 4 prn to about 1 1 pm; and

e. determining that the canine is cognitively impaired if the first body temperature is less than Q.ir^'C lower than the second body temperature

1 L The method of claim 10 wherein the first body temperature of the canine is measured at about 7 am to about 10 am.

12. T he method of ciaini 10 wherein the first body temperature of the canine is measured at about 8 am to about 10 am.

13. The method of claim 1.0 wherein the second body temperature of the canine is measured at about 5 pm to about i i pm.

14. The method of claim 10 wherein the second body temperature of the canine is measured at about 6 pm to about 8 pm.

15. The method of claim 10 wherein the second body temperature of the canine is measured at. about 7 pm.

16. The method of claim 10 wherein the canine is a dog.

17. The method of claim 16 wherein the dog is a senior dog.

18. The method of claim 1 7 wherein the senior dog Is 9 or more years of age.

1 ⁽>. The method of claim 10 wherein both the first temperature and the second temperature are less than 38 °C