Konverents-näitus
Veterinaarmeditsiin 2008
31. oktoober – 1. november
Managing the “Older” Pet
Canine Cognitive Dysfunction
Stephen Barabás BSc BVMS MRCVS1
1.VetPlus,Lytham St. Anne’s, UK
Introduction
CDS
Epidemiology
Pathology
Management
Agenda
The Geriatric Pet
Cognitive Dysfunction Syndrome (CD)
Epidemiological Surveys of Pet Owners
Patho-physiology of CD
Diagnosis
Management and treatment
Conclusion
Conclusion
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Geriatric Animals
Audience 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?
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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)
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
“Nurturing Older Dogs: attitudes and
experiences of caregivers”
Questionnaire of the caregivers in US old people’s
homes of elderly dogs kept within their
institutions
The 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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Managing the Older Dog
Counselling of the owner is the most
important factor
Help 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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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 Consult
Canine & Feline Behavior
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Clinical Signs of Cognitive Dysfunction
Disorientation
Interaction Reduction
Sleep Patterns Alterations
House Training Loss
Activity Level Reduction
An English acronym =
DISH A
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Canine Cognitive Dysfunction (CD)
incidence from USA Studies
“Most commonly affects dogs greater
than 10 yrs old”
48% of dogs >7 yrs old
62% of dogs 11-16 yrs old
100% of dogs >15 yrs old
}
Showed one or more
signs of Cognitive
Dysfunction (CD)
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Percent
“Prevalence of behavioural changes associated
with age related cognitive impairment in dogs”
Neilson et al JAVMA 2001
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Crufts Survey of UK Pet Owners
- pets over 7 years olds
Total Number of Surveys completed = 981
DOGS
Dogs
80%
80%
CATS
Cats
20%
20%
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”
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Survey of UK Owners with Pets
over 7 years old
Percent of pets
Compared to when the pets were younger:
67
60
53
44
40
31
33
20
More restless &
More confused
Less Eager to play &
Less Active
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Survey of UK Owners with Pets
over 7 years old
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
problems
46% are unaware that there are any treatments
at all
As 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.
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Survey of UK Owners with Pets
over 7 years old
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Conclusions from UK Survey
Cognitive Dysfunction in the UK seems to effect
30%+ of all pets over 7 years old
The pet owner is noticing the behavioural
changes associated with the condition
Many owners are unaware of available
treatments for older pet behaviour problems
The vast majority want more information, many
willing to attend special vet clinics to help their
pets
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Cat Cognitive Dysfunction
43% of 152 cats had one or more signs consistent
with CDS
After excluding medical cases
 28% of cats aged 11-14 years
 49% of cats aged 15-21 years old
Displayed signs consistent with cognitive dysfunction
For 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?
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Mitochondrial Energy & Free Radical Production
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Theory of Age-Related Mental Decline
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Effect of Age-Related Brain Damage
End Result = Loss of Grey and White Matter
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Patho-physiology of Cognitive Dysfunction
The decline of neuronal grey and white
matter in the frontal and cerebral brain
Increase in ventricular volume
Neurotoxic deposits (lipofuscin, ubiquitin and
β-amyloid)
Results in
 Loss of Memory
 Loss of Innate Controls
• Bladder
• Rectum
 Increase in anxiety
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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 AD
High 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)
Introduction
CDS
Epidemiology
Pathology
Management
CD Diagnostics
Eliminate other possible causes of agerelated behavioural changes




Musculoskeletal
Organ failure
Endocrinopathies, i.e. thyroid
Cardiovascular
Simple CBC and biochemistry
Urine tests
Ask appropriate behavioural screening
questions (DISHA)
Conclusion
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Prevention and Treatment of Age-Related
Cognitive Dysfunction
Calorific restriction is the only known regimen of lifestyle 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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
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
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Supplementation Studies into Reducing
Cognitive Dysfunction Symptoms
L-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, alphalipoic 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)
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Supplementation Studies into Reducing
Cognitive Dysfunction Symptoms in the Dog
Milligram’s study in Beagles tested three groups:
 Behavioural enrichment
 Supplementation
 Combination of both
Both behavioural enrichment and
supplementation reduced age-related decline
The combination had the greater protective effect
on learning ability = Synergism
Introduction
CDS
Epidemiology
Pathology
Management
Conclusion
Conclusion
Cognitive Dysfunction is recognized as an
increasing disorder in the aging pet population
Other age-related diseases need to be ruled out
first by a thorough clinical examination
Owners are acutely aware of the change in
behaviour of their “older” pets but unaware of
viable management and therapeutic options
Owners reluctant to seek veterinary advice for
fear of euthanasia being offered
Add behavioural questions to your old pet exams
Aktivait – Behavioural
Age-related Pet Supplement
Drs. Sarah Heath and Paul Craze plus all the
UK vets, nurses and dog owners
involved in the Aktivait Trial
Canine Cognitive Dysfunction
A Nutritional Supplement Trial
Stephen Barabás BSc BVMS MRCVS1
Hermann FM Bourgeois DVM2
1.VetPlus,Lytham St. Anne’s, UK
2 Takamby Consult., Panama St.
Introduction
Material
Method
Results
Discussion
Conclusion
Effect of Age-Related Brain Damage
End Result = Loss of Grey and White Matter
Introduction
Material
Method
Results
Discussion
Conclusion
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
Introduction
n = 981

Material
Method
Results
Discussion
Survey at Crufts Dog Show
Conclusion
VETPLUS, 2005
Life enjoyment
 Sleeping
 In house activity
 Eagerness to play
 Confusion
 Restless
 House Soiling
%
0
10
20
30
40
50
60
70
80
Introduction
Material
Method
Results
Discussion
Conclusion
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
Introduction
Material
Method
Results
Discussion
Conclusion
Inclusion: Exclusion Criteria
n = 44
Inclusion
Exclusion
 > 8 years old
 Medical treatments
 Owner > 2 m
 Clinical disease
 > 1 month “DISH”
 “DISH” prior to 8 yrs
 Haematology OK
 Prescription diets
 Biochemistry OK
 Agressivity level
 Maintenance diet
 < 1 clinical sign of CD
Introduction
Material
Method
Results
Discussion
Conclusion
Combination Supplement
Actives (mg)
Dogs <10 kg
Dogs >10 kg
DHA/EPA
35.0
70.0
Vitamin C
20.0
40.0
N Acetyl Cysteine
20.0
40.0
L-Carnitine
13.5
27.0
Alpha lipoic acid
10.0
20.0
Vitamin E
10.0
20.0
Acetyl L - carnitine
5.0
10.0
Co Q10
1.0
2.0
Phosphotidylserine
1.0
2.0
Selenium (µg)
25
50
Introduction
Material
Method
Results
Discussion
Oxidative Damage to the Neuron
Co Q10
Vit E, Vit C
Selenium
N-acety Cysteïne
 Lipoic acid
EPA/DHA
Phosphotidylserine
Acetyl L-carnitine
L – carnitine
Co Q10
Conclusion
HEAD E.,2008
Phosphotidylserine
Acetyl L – Carnitine
L – carnitine
Co Q10
Introduction
Mateiral
Method
Results
Discussion
Conclusion
Clinical Methodology
A
-7
1
0
10
B
21
28
42
49
2
baseline
“exit”
3
Introduction
Material
Method
Results
Discussion
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
Conclusion
Introduction
Material
Method
Results
Discussion
Conclusion
Recruitment Criteria: “DISH”
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
Introduction
Material
Method
Results
Discussion
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
Conclusion
Introduction
Material
Method
Results
Study Data
End of study
27
Out
17
 Placebo
8
 Supplement
9
Reasons
 Moving
 Disrespect of paperwork
 Non-relied clinical reasons
Discussion
Conclusion
Introduction
Material
Method
Results
Discussion
Conclusion
Improvement in cognitive score
Disorientation
Days from start of trial
p = 0.040
Introduction
Material
Method
Results
Discussion
Conclusion
Improvemnt in cognitive score
Social Interaction
Days from start of trial
p = 0.011
Introduction
Material
Method
Results
Discussion
Conclusion
Daily no awake time
Sleep pattern
Days from start of trial
p = 0.012
Introduction
Material
Method
Results
Discussion
Conclusion
Improvemnt in age related behavior
Age related behaviour
Days from start of trial
p = 0.020
Introduction
Material
Method
Results
Discussion
Conclusion
Improvemnt in cognitive score
House Soiling
Days from start of trial
p = 0.007
Introduction
Material
Method
Results
Discussion
Conclusion
Improvemnt in relationship
Owner Assessment
Days from start of trial
p = 0.014
Introduction
Material
Method
Results
Discussion
Conclusion
Global assesment score
Vet Assessment
p = 0.004
Introduction
Material
Method
Results
Discussion
Perspectives of the Trial
Number of cases
 Gender stratification
 Age related benefit?
Cross over
Impact in case of drug therapy ?
Conclusion
Introduction
Material
Method
Results
Discussion
Conclusion
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
Aktivait – Behavioural
Age-related Pet Supplement
Drs. Sarah Heath and Paul Craze plus all the
UK vets, nurses and dog owners
involved in the Aktivait Trial