Encephalopathies:Canine Cognitive Disease
Encephalopathies
• Forebrain– 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 thewrong 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
• 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
Treatment of CCDCholinergic Agents• Conventional Medicines
– Acetylcholinesterase Inhibitors• Donepezil (Aricept)• Galantamine (Razadyne)• Rivastigmine (Exelon)• Tacrine (Cognex)
– Cholinergic Receptor Agonists• Bethanechol (Urecholine)
• Natural Medicines– Acetylcholinesterase Inhibitors
• Huperzine A
– Acetylcholine Precursors• Acetyl-L-carnitine• Alpha-GPC• Choline• DMAE (Dimethylaminoethanol)• Lecithin• Phosphatidylcholine• Phosphatidylserine
NMDA Inhibitors• Conventional Medicines
– Memantine (Namenda)
• Natural Medicines– Huperzine A
Antioxidants• Conventional Medicines
– Selegiline (Eldepryl)
• Natural Medicines– 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