Encephalopathies Canine Cognitive Disease Encephalopathies Forebrain Altered mentation

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 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 6 x 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 • 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 • • 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 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