1. Encephalopathies: Canine Cognitive Disease

2. 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

3. Disorders Affecting Brain Degenerative –Lysosomal storage disease –Leukodystrophies –Neuronal vacuolation of Rottweilers & Boxers –Neuronal Abiotrophy of Cockers –Canine Cognitive Dysfunction

4. 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.

5. Normal vs. Abnormal Aging >40 year-old: Age Associated Memory Impairment Decline in Hepatic & Renal function Vision changes Hearing changes

6. 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

7. 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

8. 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

9. 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

10. Genetics The two major risk factors for dementia –age –family history Alzheimer’s: 50% penetrance in first degree relatives by age 80

11. 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

12. 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

13. Clinical Features Memory Impairment Early Dementia: –difficulty learning and retaining new information Late Dementia: –inability to access distant memories, impaired judgment and executive function

14. 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

15. Clinical Features Early behavior and mood changes are common: –personality alterations –irritability –anxiety –Depression Late findings: Delusions, hallucinations, aggression and wandering

16. 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

17. Mild Dementia Disorientation for dates Naming difficulties (anomia) Recent recall problems Difficulty copying figures Decreased insight Social withdrawal Irritability, mood changes Problems managing finances

18. 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

19. Severe Dementia Unintelligible speech Remote memory gone Inability to copy or write Loss of self care Incontinent

20. 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

21. CCD MRI FIndings

22. 5 year old Siberian Husky

23. De Novo Hydrocephalus

24. Pierre

26. 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

27. Treatment of CCD Cholinergic 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)DMAEDimethylaminoethanol Lecithin Phosphatidylcholine Phosphatidylserine NMDA Inhibitors Conventional Medicines –Memantine (Namenda) Natural Medicines –Huperzine AHuperzine A Antioxidants Conventional Medicines –Selegiline (Eldepryl) Natural Medicines –Beta-caroteneBeta-carotene –Ginkgo leaf (Ginkgo biloba)Ginkgo leaf –Vitamin CVitamin C –Vitamin EVitamin E

28. 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