Cognitive Dysfunction Syndrome in Dogs. G. M. Landsberg DVM, DACVB, DECAWBM

Transcription

1 Cognitive Dysfunction Syndrome in Dogs G. M. Landsberg DVM, DACVB, DECAWBM

2 Growing Old with Grace

3 Conflict of Interest Disclosure I have financial interest, arrangement or affiliation with: North Toronto Veterinary Behaviour Specialty Clinic CanCog Technologies - Vice President, Veterinary Affairs Contracted Research Purina Pet Care Hills Pet Nutrition Neutricks LLC Innovet / CEVA Animal Health Virbac Animal Heatlh

4 Cogni2ve Dysfunc2on Syndrome Decline in awareness / altered response to stimuli Learning and Memory Deficits DISHA Disorientation (D) Social interactions (I): or Sleep/wake (S) Housesoiling (H) + learning / memory Activity (A): or aimless with CDS Anxiety

5 Clinical Signs Distribu2on Fast et al dogs >8 Cognitive dysfunction daytime sleep / restless night 57% Altered social interactions 51% Confusion 49% Anxiety 46% Borderline dysfunction Daytime sleep 70% Anxiety 11% No CCD - 4% anxiety

6 Confusion Awareness Meeka 14.5 yr F(S) Border Collie

7 Anxiety Teagan 9 yr F(S) German Shepherd

8 Learning and Memory Principle sign pet vs. laboratory studies Pets soiling, commands, tasks 11+ years Ability to learn complex tasks declines by 6-8 years

9 Behaviour Signs in Senior Pets Owner presented concerns Referrals / VIN prevalence Pet problem / owner problem Fear / anxiety 74% - phobias 18%, Night wake 32%, confusion 26% General practice Owners infrequently report unless clinically significant for owner / pet

10 General Prac2ce Owner may not report Pfizer >7: 48% at least one CDS sign 17% report Salvin: 14% signs 1.9% diagnosed 87% missed Madari: mild owners not notice / report unless asked Mongillo senior more attached - signs more passive Owner education screening questionnaire Signs to identify cognitive / medical Senior pets can be helped early intervention

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12 Clinical Signs / Prevalence Neilson et al (n=180) DISHA - retrospective 11-12: 28% mild / 10% severe 15-16: 68% mild - 35% severe Salvin et. al 2009 (n-497) internet Overall 14.2% : 5% / 12-14: 23% / over 14: 41% Katina et al, 2016 DISH n=300 prospective %; %; % - 100% Overall 74% 28% medical problems

13 CDS Onset and Progression Madari et al, 2015 Over 6 mo - 42% none to mild 24% mild to moderate Over 1 yr 71% none to mild 50% mild to moderate Salvin 8 and over progression over 6 months ½ items showed 10% deterioration 2/3 severity Medical / Physical, vs. Cognitive

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15 Proac2ve senior health care Behaviour as sign of disease / CDS Owner education owners must advise Senior pets can be helped diagnose / start early Twice yearly screening Exam / neuro - Blood / urine BP Behaviour screening questionnaire

16 Healthy Dog / Cat Screening Blood, Urine, Blood pressure Cat Screening (n=100) Azotemia 9% SG < % Elevated TT4 6% DiabeNc 1% UTI 1% Dog Screening (n=90) Low TT4 29% Increased SAP 17% Increased UCCR 16% UCCR + SAP 4% Pyuria / bacteriuria 12% Garcia, BruyeQe: ACVIM 1998, 8 years +

17 Cogni2ve Decline / Dysfunc2on Diagnosis of Exclusion Metabolic / endocrine Neurologic / sensory Musculoskeletal Signs questionnaire History video Physical exam Diagnostics by signs and if you re the owner of a very old dog, this lirle baby comes with a speaker that amplifies the sound of the can being opened.

18 Canine Brain Aging 1. cognitive decline as in humans 2. social relationships 3. parallels in age-associated brain pathology ventricles enlarge / vascular compromise neuron loss decrease frontal lobe volume amyloid-beta tau hyperphosphorylation increased toxic free radicals cholinergic decline Decline in brain metabolic rate 4. measurable deficits in learning, memory Analogous to early human Alzheimers (AD)

19 Brain metabolic rate for glucose Significant reducnon 6 years compared to 1 year Metabolic rate of glucose (umol/100 g/min) Year 3 Years 6 Years Years Years Ages Frontal cortex Hippocampus Basis of Midbrain Pons Neurobiology of Aging, 4: , 1983

20 Toronto General Test Apparatus (TGTA) Object Approach - Discrimination Reversal Attention Oddity Egocentric Landmark - DNMP Discriminanda Sliding tray Test box - (location of animal) Food well

21 Canine Discrimination and Reversal 140 Errors to Criterion (Mean) Senior Old Middle Aged Young 20 0 Size Discrimination TASK Reversal Complex Associative Learning (Head et al, 1998, Neurobiol Aging) and Executive Function Deficits (Milgram et al, 1994, Behav Neurosci) Young 2-4, Middle Age 5-7, Old 8-11, Senior 12+ Success: 8/10, 9/12 3 days

22 Canine Discrimina2on and Reversal

23 Variable Object Oddity Selec2ve ARen2on Complex discrimina2on

24 DNMP Delayed Non Matching to PosiNon Single object with food Food in non-matching posinon Add in increasing delay

25 Therapeu2c Approaches to Canine Demen2a

26 Treatment of CDS

27 All medical - concurrent Limits / Expectations Enrichment limitations Treatment Social - play / exercise / train Object work for food Environmental management Behavior modification Drugs / natural Start early CDS Adjunctive sleep / anxiety

28 Enrichment Needs vs. limitanons age / health physical / mental

29 Grace 12 years f(s) - NSDTR Excessive whining, restless Less responsive Housesoil What does your dog want? Restore the bond Medical Hearing / visual decline Arthritis / less mobile Low FT4

30 Grace: 20/12/85 24/12/01 Selegiline 4 y. - b/d TM 4 m. More responsive Normal sleep (13 hr) Whining within limits Enrichment Thyroid 5+ years Meloxicam 3 yr. Theophylline 1 year Obesity - always

31 Drug therapy CDS Selegiline - MAOB inhibition (N Am) CanCog + clinical Enhance catecholamine transmission - Anti-oxidant Nicergoline - alpha 1 and 2 adrenergic antagonist cerebral blood flow; enhance neuronal transmission Propentofylline - Xanthine derivative blood flow - decrease thrombus Cholinergic decline avoid anticholinergics ACH inhibitors? Memantine NMDA antagonist- block glutamate Stem cell implant immunotherapy

32 Dietary TherapeuNcs Prevalence by 2.8X with high quality commercial (vs. low quality commercial / kitchen waste) - Katina et. al, 2016 Hills b/d diet Mitochondrial co-factors l-carninne, alpha-lipoic acid AnNoxidants flavonoids, carotenoids, Vitamins E and C, Selenium, beta-carotene EssenNal faqy acids Clinical + CanCog - 8 wks 2 yrs. (Landmark, Oddity, Reversal) 2 years - Diet + Enrich > Enrich > Diet > Control

33 Dietary TherapeuNcs Purina Bright Minds 5.5% - Neurocare 6.5% + BPB Medium Chain Triglycerides to produce ketone bodies (βhydroxybutyrate) as alternanve energy for aging neurons CanCog: 5.5% MCT: d Landmark / Egocentric / Oddity Clinical Trial: CDS 6.5% MCT + BPB (also adjunct to Epilepsy) DISHAA: MCT 5/6 improved 30 d 6/6 at 90 days vs. placebo 3/6 at 30 days and 4/6 at 90 days not disorientanon / social Arginine - nitric oxide synthesis - bp, circulanon, cogninon EPA, DHA deficiency - ann-inflammatory B Vitamins cogninve support, acetylcholine, annoxidant AnNoxidants Selenium, Vitamins E and C

34 Natural TherapeuNcs Supplements Senilife: PhosphaNdylserine, resveratrol, gingko biloba, vitamins B6 & E Clinical + CanCog improve (canine) + feline AcNvait: phosphandylserine, faqy acids, vitamins E & C, l-carninne, α-lipoic acid, coenzyme Q, Selenium Canine (clinical trial) and feline S-adenosylmethionine (Novifit) - methyl donor Clinical (canine) + CanCog improve (canine and feline)

35 S-adenosylmethionine on age related mental decline Rème, CA et al. Vet Ther, 2008 n=17 Novifit / n=19 placebo 2 signs of DISHAA Parameter evaluated Placebo Novifit Decreased awareness * Decreased ac2vity * Decreased rela2onship with owner 36.8* 47.1* Learning deficits * Increased total dura2on of sleep * *Significant reduction from day 0

36 Natural TherapeuNcs Supplements Apoaequorin (Neutricks) - Calcium buffer CanCog improve (canine) + feline Senior Vitality Mitochondrial factors, AnNoxidants DHA, L-carniNne, Lutein, Vitamins C, E, A, Selenium and addinonal B vitamins and minerals Huperzine A, curcurmin, fish oils, phosphandylserine

37 Decreased ac2vity - less responsive Sam 9 yr. M (n) Shelty Decreased activity Less responsiveness Arthritis (carprofen) Deaf? BAER refer neurology Vision? refer ophthalmology CBC / Chem / T4 / Urine nsf Canine b/d TM

38 Sam Shelty 30 day follow-up Ophthalmology referral - corneal dystrophy Hearing resolved no referral / BAER Attentive - responsive Active / Interactive

39 Sessions on Aging and Cognition, Disorders and Therapeutics Welcome Reception - Gourmet Wine Pairing Dinner Patrick Pageat, Aladar Madari, Tomas Camps, Tomas Smolek, Joseph Araujo, Paolo Mongillo, Gary Landsberg, Bill Milgram, Gary Pan and more August 19, 20 Short course on Research Protocols and tour of CanCog Visit canineconference.com or contact Gary Landsberg at garyl@cancog.com

40 G DAY EH!