Transcript CanineCognitiveDisease

Encephalopathies:
Canine Cognitive Disease
Encephalopathies
• Forebrain
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Altered mentation
Behavioral changes
Wide forced circling
Head-pressing
Visual deficits
Hemineglect
Seizures
CP deficits with fairly
good gait
• Brainstem
– Altered mentation
– CP deficits with gait
abnormalities
– CN deficits
– Vestibular dysfunction
Disorders Affecting Brain
• Degenerative
– Lysosomal storage
disease
– Leukodystrophies
– Neuronal vacuolation
of Rottweilers &
Boxers
– Neuronal Abiotrophy
of Cockers
– Canine Cognitive
Dysfunction
Canine Cognitive Deficit Syndrome
A. 15-year-old female mixed breed attempting to enter door from the
wrong side; B. stuck in corner, not knowing to back out.
Normal vs. Abnormal Aging
• >40 year-old: Age Associated Memory
Impairment
• Decline in Hepatic & Renal function
• Vision changes
• Hearing changes
Dementia
• Definition: The loss of cognitive and
intellectual function, without impairment of
perception or consciousness
• Characterized by disorientation, impaired
memory, judgment, intellect and labile affect
Did you Know…
• Five major types of Dementia
– Alzheimer’s: 60-70%
– Cerebrovascular: 15-25%
– Lewybody: 5-8%
– Frontotemporal: 3-5%
– Parkinson's with Dementia: 1-3%
• Estimated by 2040, 120 million
Arch Neuro, 2005
Did you Know…
• Prevalence: 6-8% 60 yrs and doubles
every 5 years
• 80 yrs: 47-50% population suffer from
some form of dementia
www.aoa.dhhs.gov
Did you Know…
• 2006 - total cost world wide exceeded
$220 billion
– acute care
– long-term care
– home health care
– lost productivity for caregivers
www.aoa.dhhs.gov
Genetics
• The two major risk factors for dementia
– age
– family history
• Alzheimer’s: 50% penetrance in first
degree relatives by age 80
Genetics
• Alzheimer’s (AD): before age 60
– genetic mutations on chromosomes 1, 14, 21
• Alzheimer’s (AD): after age 60
– apolipoprotein E gene (APOE) on chromosome
19
Genetics
• APOE* 4/4 allele 6x increase risk in (AD)
• APOE* 2 appears to be protective
• Other risk factors:
– head injury, education level, estrogen
replacement after menopause, long-term
NSAID’s
Clinical Features
• Memory Impairment
• Early Dementia:
– difficulty learning and retaining new
information
• Late Dementia:
– inability to access distant memories, impaired
judgment and executive function
Clinical Features
• Dementia has a profound effect on the
patient’s daily life:
– ADL’S (eating, bathing, grooming)
– planning meals
– managing finances
– medications
– communication
– driving
Clinical Features
• Early behavior and mood changes are
common:
– personality alterations
– irritability
– anxiety
– Depression
• Late findings: Delusions, hallucinations,
aggression and wandering
Clinical Features
• Dementia and depression often overlap
• Depressed patients usually exhibit intact
language and motor skills
• 55% over 65 yrs with mild cognitive
impairment + depression, progress to
moderate to severe dementia within 5 yrs
Arch Neuro, 2005
Mild Dementia
• Disorientation for
dates
• Naming difficulties
(anomia)
• Recent recall
problems
• Difficulty copying
figures
• Decreased insight
• Social withdrawal
• Irritability, mood
changes
• Problems managing
finances
Moderate Dementia
• Disoriented to date
and place
• Comprehension
difficulties
• Impaired new learning
• Getting lost in familiar
areas
• Impaired calculating
skills
• Delusions, agitation,
aggression
• Stop cooking,
shopping, banking
• Restless, anxious,
depressed
• Problems with
dressing, grooming
Severe Dementia
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Unintelligible speech
Remote memory gone
Inability to copy or write
Loss of self care
Incontinent
CCD vrs AD
• CCD
– Elderly animals
– Similar Path
• Cerebral vascular
changes, meningeal
thickening, gliosis &
ventricular dilation
– Beta-amyloid protein
– Tau protein
• AD
– Elderly people
– Similar Path
• Cerebral vascular
changes, meningeal
thickening, gliosis &
ventricular dilation
– Beta-amyloid protein
– Tau protein
CCD MRI FIndings
5 year old Siberian Husky
De Novo Hydrocephalus
Pierre
Pierre
Hydrocephalus Patterns
• Kidney & Spleen Qi
Deficiency
– Younger animals with
congenital hydrocephalus
• Kidney & Liver Yin/Blood
Deficiency
– Older animals with Canine
Cognitive Disease
• Liver Qi Stagnation
– Secondary to CNS
inflammatory disease or cancer
Treatment of CCD
Cholinergic Agents
NMDA Inhibitors
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Conventional Medicines
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Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon)
Tacrine (Cognex)
Cholinergic Receptor Agonists
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Bethanechol (Urecholine)
Natural Medicines
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Acetylcholinesterase Inhibitors
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Acetylcholinesterase Inhibitors
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Huperzine A
Acetylcholine Precursors
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Acetyl-L-carnitine
Alpha-GPC
Choline
DMAE (Dimethylaminoethanol)
Lecithin
Phosphatidylcholine
Phosphatidylserine
Conventional Medicines
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Memantine (Namenda)
Natural Medicines
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Huperzine A
Antioxidants
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Conventional Medicines
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Selegiline (Eldepryl)
Natural Medicines
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Beta-carotene
Ginkgo leaf (Ginkgo biloba)
Vitamin C
Vitamin E
Treatment of CCD
• Selegiline
– 0.5-1 mg/kg QD AM
– FDA approved
– 69% improved vrs 52%
placebo
• Vitamin E (& other
antioxidants)
– Up to 50 mg/kg
• Ginkgo biloba
– 1-2 mg/kg BID extract
• Acetylcysteine
– 5-25 mg/kg BID
• St John’s wort
– 2-4 mg/kg
• Huperzine A
– 1-2 µg/kg