Konverents-näitus Veterinaarmeditsiin 2008 31. oktoober – 1. november

Konverents-näitusVeterinaarmeditsiin 2008

31. oktoober – 1. november

Managing the “Older” PetCanine Cognitive Dysfunction

Managing the “Older” PetCanine Cognitive Dysfunction

Stephen Barabás BSc BVMS MRCVS1

1.VetPlus,Lytham St. Anne’s, UK

Agenda

The Geriatric PetCognitive Dysfunction Syndrome (CD)Epidemiological Surveys of Pet OwnersPatho-physiology of CDDiagnosisManagement and treatmentConclusion

Introduction CDS Epidemiology Pathology Management Conclusion

Geriatric AnimalsAudience Practising Vet Questions

How many good clients do you have attending your practice?

• 500• 1000• >2000

How many vets in this auditorium have >20% + of their clients pets >8 years old?

Are these clients loyal customers? Are they willing to spend money to help their “old

friend”? Is time and lifestyle a factor in their decision? Do there

pets get neglected in this busy world?


Geriatric Animals

Dogs and Cats are living longer Dogs living for 12 + years Not uncommon for 20+ year old cat

Diseases become more similar to human aging population

Thyroid disorders Pituitary – adrenal gland disorders General organ system failure Cancer Cognitive Dysfunction Syndrome (CD)


UK survey of dog owners in 2000

30% of the UK dogs were >8 years old

Owners expect pets to live >13 years

Increased expectation of healthcare and quality of life for older dogs and cats

Better Foods and supplements Better understanding of general health care Better drugs and vaccines


“Nurturing Older Dogs: attitudes and experiences of caregivers”

Questionnaire of the caregivers in US old people’s homes of elderly dogs kept within their institutionsThe caregivers felt the older dogs were:

More mellow Less excitable More devotion and loving than younger dog

Rewards of Companionship >> Time and Expense of looking after an older dog

JAVMA 2001 – Hart et al


Managing the Older Dog

Counselling of the owner is the most important factorHelp them understand the biological changes in health and behaviour of their aging pet

40% of owners with dogs 11-12 yrs old have visual impairment

50% of 11-12 yrs old and 90% of owners with dogs 15-16 yrs old had hearing impairment

• Hand signals, Jumping on the spot, tactile directions

Dental problems will increase with age – cleaning and brushing will prevent problems


Managing the Older Dog

Adapt household to help arthritic animal Elevated food/water bowls Comfortable/Warm bedding Avoid slippery floors i.e. Rugs and Mats

Anxieties can increase resulting in behavioural changes with age

Separation anxiety House soiling Sleep-wake cycle problems

Canine and Feline Behavior Therapy 2nd Edition


What is Cognitive Dysfunction?

“Cognitive Dysfunction is a syndrome associated with brain aging. The brain

changes lead to alterations in awareness, decreased responsiveness to stimuli, and deficits in learning and memory. Subtle

changes are seen in early stages, referred to as cognitive decline.”

Blackwell’s Five-Minute Veterinary ConsultCanine & Feline Behavior


What is Cognitive Dysfunction?

Medical condition Compromised cerebral blood flow Depletion in neurotransmitters such as

dopamine Increased levels of free radicals

• Leading to cell injury and brain pathology

Main signs are Behavioural Disorientation

Loss of House Training Changes in Sleep Patterns Reduced Social Interaction

Ensure that a full clinical exam eliminates other causes of behavioural changes


Clinical Signs of Cognitive Dysfunction

Disorientation

Interaction Reduction

Sleep Patterns Alterations

House Training LossActivity Level Reduction

An English acronym = DISHA


Canine Cognitive Dysfunction (CD) incidence from USA Studies

“Most commonly affects dogs greater than 10 yrs old”

48% of dogs >7 yrs old62% of dogs 11-16 yrs old100% of dogs >15 yrs old

Showed one or more signs of Cognitive Dysfunction (CD)}


“Prevalence of behavioural changes associated with age related cognitive

impairment in dogs”

Per

cent

Neilson et al JAVMA 2001


Total Number of Surveys completed = 981

Average age of pets in the survey Dogs 11 years Cats 13 years Most people think one pet year is equivalent of

7 human years, therefore 9 year old animals are approaching “retirement age”

Crufts Survey of UK Pet Owners - pets over 7 years olds


Dogs 80%

Cats 20%

Crufts Survey of UK Pet Owners - pets over 7 years olds

Questions asked about awareness of problems and treatments as well as clinical signs in their own pet

93% think that pets should get the same or better medical treatment than themselves

31% already giving supplements on a daily basis


Compared to when the pets were younger:

Per

cent

of

pets

House

Soili

ng

House

Soili

ngD

isorie

ntat

ion

Diso

rient

atio

n

Inter

actio

n

Inter

actio

nSl

eep

Patter

ns

Slee

p Pat

terns

Qua

lity o

f Life

Qua

lity o

f Life

Reduc

ed

Reduc

ed

20

40

60

More restless &More confused

Less Eager to play &Less Active

Survey of UK Owners with Pets over 7 years old

44

67

53

3331


However, despite owners being able to see the signs

of Cognitive Dysfunction:Only 7% of owners feel well informed about treatments available for older pet behavioural problems46% are unaware that there are any treatments at allAs a result of this, they may not see the point in seeking advice. Owners fear that euthanasia would be the only recommendation by the vet if no treatments are available.



80% of owners would like more access to information about older pets – 61% would like to attend clinics for older pets

83% of owners would want advice and treatment of pets diagnosed with age related behavioural disorders



Conclusions from UK Survey

Cognitive Dysfunction in the UK seems to effect 30%+ of all pets over 7 years oldThe pet owner is noticing the behavioural changes associated with the conditionMany owners are unaware of available treatments for older pet behaviour problemsThe vast majority want more information, many willing to attend special vet clinics to help their pets


Cat Cognitive Dysfunction

43% of 152 cats had one or more signs consistent with CDSAfter excluding medical cases

28% of cats aged 11-14 years 49% of cats aged 15-21 years old

Displayed signs consistent with cognitive dysfunctionFor instance,

Does the cat continue to use the little box on a regular basis?

Does the cat continue to groom and show interest in household activities?


What causes Cognitive Dysfunction?

Mitochondrial Energy & Free Radical Production


Theory of Age-Related Mental Decline


End Result = Loss of Grey and White Matter

Effect of Age-Related Brain Damage


Patho-physiology of Cognitive Dysfunction

Cummings et al 1998 Accumulation of β-amyloid deposits in

frontal and hippocampus in dogs with increased cognitive dysfunction

Almost identical to Alzheimer disease in humans

Cummings et al 1996 Degree of β-amyloid deposits in the dog

brain was proportional to the degree of impairment in learning complex tasks


Patho-physiology of Cognitive Dysfunction

The decline of neuronal grey and white matter in the frontal and cerebral brainIncrease in ventricular volumeNeurotoxic deposits (lipofuscin, ubiquitin and β-amyloid)Results in

Loss of Memory Loss of Innate Controls

• Bladder• Rectum

Increase in anxiety


Effects of Gonadectomy on Cognitive Dysfunction

Human research and laboratory research has shown beneficial effects of oestrogen and testosterone for neuron survival and adaptive growth (Haskell et al 1997; Yaffe et al 1998)

Ovariectomy may predispose women to ADHigh correlation with men diagnosed with AD and low levels of free testosterone

Study of aging dogs and cognitive dysfunction: Intact males only showed mild signs of CD Neutered males about 50% showed severe stage CD

behavioural changes (Hart B.L. JAVMA 2001)


CD Diagnostics

Eliminate other possible causes of age-related behavioural changes

Musculoskeletal Organ failure Endocrinopathies, i.e. thyroid Cardiovascular

Simple CBC and biochemistryUrine testsAsk appropriate behavioural screening questions (DISHA)


Prevention and Treatment of Age-Related Cognitive Dysfunction

Calorific restriction is the only known regimen of life-style change that increases the life-span of animals

Most important aspects to control are: Maintenance of mitochondrial function Control of oxidant production Production of neurotransmitters


Prevention and Management of Age-Related Cognitive Dysfunction

Supplementation of diet with specific metabolites:

Metabolic enhancers Neurotransmitter enhancers Antioxidant damage preventers

Drugs i.e. L-deprenyl HCl an MAO B inhibitor


Management of Cognitive Dysfunction

L-deprenyl HCl (Selegiline) = ameliorates signs of CD in some dogs.

Reduces depletion of dopamine & some neuroprotective and antioxidant support

Numerous drugs contraindicated with its use Side effects in several different trials

Nicergoline (alpha 1&2 adrenergic antagonist) Increase cerebral blood flow, enhance neuronal transmission,

and have a neuroprotective effect

Propentofylline Inhibit platelet aggregation and blood flow


Supplementation Studies into Reducing Cognitive Dysfunction

SymptomsL-Carnitine and alpha-lipoic acid fed to old rats

Reversed age-related mitochondrial degeneration Lowered oxidative damage in liver cells Increased the binding affinity of brain and memory

related enzymes (Hageb et al 1998; Liu et al 2002)

1 year study in old dogs with L-Carnitine, alpha-lipoic acid, and vitamins E and C supplemented

Significantly reduced the impairment that aged dogs showed on difficult discrimination tasks (Milligram et al 2002 and 2005)


Supplementation Studies into Reducing Cognitive Dysfunction

Symptoms in the DogMilligram’s study in Beagles tested three groups:

Behavioural enrichment Supplementation Combination of both

Both behavioural enrichment and supplementation reduced age-related declineThe combination had the greater protective effect on learning ability = Synergism


ConclusionCognitive Dysfunction is recognized as an increasing disorder in the aging pet populationOther age-related diseases need to be ruled out first by a thorough clinical examinationOwners are acutely aware of the change in behaviour of their “older” pets but unaware of viable management and therapeutic optionsOwners reluctant to seek veterinary advice for fear of euthanasia being offeredAdd behavioural questions to your old pet exams


Drs. Sarah Heath and Paul Craze plus all the UK vets, nurses and dog owners

involved in the Aktivait Trial

Aktivait – BehaviouralAge-related Pet Supplement

Canine Cognitive Dysfunction A Nutritional Supplement TrialCanine Cognitive Dysfunction A Nutritional Supplement Trial

Stephen Barabás BSc BVMS MRCVS1

Hermann FM Bourgeois DVM2

1.VetPlus,Lytham St. Anne’s, UK2 Takamby Consult., Panama St.

Introduction Material Method Results Discussion Conclusion

End Result = Loss of Grey and White Matter

Effect of Age-Related Brain Damage

What Causes Canine Cognitive Dysfunction?

Physiological condition

Compromised cerebral blood flow

Depletion in neurotransmitters: dopamine…

Increased levels of free radicals

Behavioral signs “DISH”

D isorientation

I nteraction

S leep Pattern

H ouse Training


Survey at Crufts Dog Show VETPLUS, 2005 n = 981

0 10 20 30 40 50 60 70 80

House Soiling

Restless

Confusion

Eagerness to play

In house activity

Sleeping

Life enjoyment

%


Supplementation Canine CD Trial

Objective: To assess the therapeutic effect of a nutritional

supplement including anti-oxidants in the

management of CDD in dogs

Type Multi-centered

• 20 veterinary practices

• Geographically dispersed

• Duration: 56 days

Placebo controlled

Double-blinded


Inclusion: Exclusion Criteria

n = 44

Inclusion

> 8 years old

Owner > 2 m

> 1 month “DISH”

Haematology OK

Biochemistry OK

Maintenance diet

Exclusion

Medical treatments

Clinical disease

“DISH” prior to 8 yrs

Prescription diets

Agressivity level

< 1 clinical sign of CD


Combination Supplement

Actives (mg) Dogs <10 kg Dogs >10 kg

DHA/EPA 35.0 70.0Vitamin C 20.0 40.0N Acetyl Cysteine 20.0 40.0L-Carnitine 13.5 27.0Alpha lipoic acid 10.0 20.0Vitamin E 10.0 20.0Acetyl L - carnitine 5.0 10.0Co Q10 1.0 2.0Phosphotidylserine 1.0 2.0Selenium (µg) 25 50


Oxidative Damage to the Neuron HEAD

E.,2008

Co Q10Vit E, Vit CSeleniumN-acety Cysteïne Lipoic acid

PhosphotidylserineAcetyl L – CarnitineL – carnitineCo Q10

Acetyl L-carnitineL – carnitineCo Q10

EPA/DHAPhosphotidylserine


Clinical Methodology

-7 0 10 21 28 42 49

baseline

2

3

1

“exit”

Introduction Mateiral Method Results Discussion Conclusion

BA

Recruitment Criteria: “DISH”

D isorientation Delay or lack of recognition

• people• animals • places

I nteractions social interactions

• people• animals • other pets

display of aggressive behavior


S leep Pattern

sleep during daytime

sleep at night

incidence of restlessness during sleep

H ouse Training

incidence of house soiling

inappropriate toileting in a variety of

locations

in sitting at inappropriate doors


Recruitment Criteria: “DISH”

Clinical Behaviour Scoring

Referring to baseline – based on differences Insignificant 0

Mild 1

Significant 2

Moderately severe 3

Very severe 4

Semi quantitative Number of incidents

Global owner evaluation

p < 0.05 statistically significant


Study Data

End of study 27

Out 17

Placebo 8

Supplement 9

Reasons

Moving

Disrespect of paperwork

Non-relied clinical reasons


DisorientationIm

prov

emen

t in

cogn

itive

sc

ore

Days from start of trial

p = 0.040


Social Interaction


Impr

ovem

nt in

cog

niti

ve

scor

e

p = 0.011


Sleep pattern


Dai

ly n

o aw

ake

tim

e

p = 0.012


Age related behaviour


Impr

ovem

nt in

age

rel

ated

be

havi

or

p = 0.020


Impr

ovem

nt in

cog

niti

ve

scor

eHouse Soiling


p = 0.007


Owner Assessment


Impr

ovem

nt in

re

lati

onsh

ip

p = 0.014


Glo

bal a

sses

men

t sc

oreVet Assessment

p = 0.004


Perspectives of the Trial

Number of cases

Gender stratification

Age related benefit?

Cross over

Impact in case of drug therapy ?


The combination of supplements in this

Nutraceutical appears to help

in the management of the behavioural clinical

signs of the “old dog syndrome”

+ve Changes in age-related behaviour signs

+ve Perception by owner and vet in dogs’ condition

The combination of supplements in this

Nutraceutical appears to help

in the management of the behavioural clinical

signs of the “old dog syndrome”

+ve Changes in age-related behaviour signs

+ve Perception by owner and vet in dogs’ condition


Drs. Sarah Heath and Paul Craze plus all the UK vets, nurses and dog owners

involved in the Aktivait Trial

Aktivait – BehaviouralAge-related Pet Supplement

Documents

Konverents-näitus Veterinaarmeditsiin 2008 31. oktoober – 1. november