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