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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 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 • 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 – – Donepezil (Aricept) Galantamine (Razadyne) Rivastigmine (Exelon) Tacrine (Cognex) Cholinergic Receptor Agonists • • Bethanechol (Urecholine) Natural Medicines – Acetylcholinesterase Inhibitors • – – 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