Konverents-näitus Veterinaarmeditsiin 2008 31. oktoober – 1. november

1. Konverents-näitus Veterinaarmeditsiin 2008 31. oktoober – 1. november

2. Managing the “Older” PetCanine Cognitive Dysfunction Stephen Barabás BSc BVMS MRCVS1 1.VetPlus,Lytham St. Anne’s, UK

4. Introduction CDS Epidemiology Pathology Management Conclusion Agenda • The Geriatric Pet • Cognitive Dysfunction Syndrome (CD) • Epidemiological Surveys of Pet Owners • Patho-physiology of CD • Diagnosis • Management and treatment • Conclusion

5. Introduction CDS Epidemiology Pathology Management Conclusion Geriatric Animals • Audience Practising Vet Questions • How many good clients do you have attending your practice? • 500 • 1000 • >2000 • How many vets in this auditorium have >20% + of their clients pets >8 years old? • Are these clients loyal customers? • Are they willing to spend money to help their “old friend”? • Is time and lifestyle a factor in their decision? Do there pets get neglected in this busy world?

6. Introduction CDS Epidemiology Pathology Management Conclusion Geriatric Animals • Dogs and Cats are living longer • Dogs living for 12 + years • Not uncommon for 20+ year old cat • Diseases become more similar to human aging population • Thyroid disorders • Pituitary – adrenal gland disorders • General organ system failure • Cancer • Cognitive Dysfunction Syndrome (CD)

7. Introduction CDS Epidemiology Pathology Management Conclusion UK survey of dog owners in 2000 • 30% of the UK dogs were >8 years old • Owners expect pets to live >13 years • Increased expectation of healthcare and quality of life for older dogs and cats • Better Foods and supplements • Better understanding of general health care • Better drugs and vaccines

8. Introduction CDS Epidemiology Pathology Management Conclusion “Nurturing Older Dogs: attitudes and experiences of caregivers” • Questionnaire of the caregivers in US old people’s homes of elderly dogs kept within their institutions • The caregivers felt the older dogs were: • More mellow • Less excitable • More devotion and loving than younger dog • Rewards of Companionship >> Time and Expense of looking after an older dog JAVMA 2001 – Hart et al

9. Introduction CDS Epidemiology Pathology Management Conclusion Managing the Older Dog • Counselling of the owner is the most important factor • Help them understand the biological changes in health and behaviour of their aging pet • 40% of owners with dogs 11-12 yrs old have visual impairment • 50% of 11-12 yrs old and 90% of owners with dogs 15-16 yrs old had hearing impairment • Hand signals, Jumping on the spot, tactile directions • Dental problems will increase with age – cleaning and brushing will prevent problems

10. Introduction CDS Epidemiology Pathology Management Conclusion Managing the Older Dog • Adapt household to help arthritic animal • Elevated food/water bowls • Comfortable/Warm bedding • Avoid slippery floors i.e. Rugs and Mats • Anxieties can increase resulting in behavioural changes with age • Separation anxiety • House soiling • Sleep-wake cycle problems Canine and Feline Behavior Therapy 2nd Edition

11. IntroductionCDS Epidemiology Pathology Management Conclusion What is Cognitive Dysfunction? “Cognitive Dysfunction is a syndrome associated with brain aging. The brain changes lead to alterations in awareness, decreased responsiveness to stimuli, and deficits in learning and memory. Subtle changes are seen in early stages, referred to as cognitive decline.” Blackwell’s Five-Minute Veterinary Consult Canine & Feline Behavior

12. Introduction CDSEpidemiology Pathology Management Conclusion What is Cognitive Dysfunction? • Medical condition • Compromised cerebral blood flow • Depletion in neurotransmitters such as dopamine • Increased levels of free radicals • Leading to cell injury and brain pathology • Main signs are Behavioural • Disorientation • Loss of House Training • Changes in Sleep Patterns • Reduced Social Interaction • Ensure that a full clinical exam eliminates other causes of behavioural changes

13. Introduction CDSEpidemiology Pathology Management Conclusion Clinical Signs of Cognitive Dysfunction • Disorientation • Interaction Reduction • Sleep Patterns Alterations • House Training Loss • Activity Level Reduction A An English acronym = DISH

14. Introduction CDS Epidemiology Pathology Management Conclusion Canine Cognitive Dysfunction (CD) incidence from USA Studies • “Most commonly affects dogs greater than 10 yrs old” • 48% of dogs >7 yrs old • 62% of dogs 11-16 yrs old • 100% of dogs >15 yrs old } • Showed one or more signs of Cognitive Dysfunction (CD)

15. Introduction CDS Epidemiology Pathology Management Conclusion “Prevalence of behavioural changes associated with age related cognitive impairment in dogs” Percent Neilson et al JAVMA 2001

16. Introduction CDS Epidemiology Pathology Management Conclusion Crufts Survey of UK Pet Owners - pets over 7 years olds • Total Number of Surveys completed = 981 • Average age of pets in the survey • Dogs 11 years • Cats 13 years • Most people think one pet year is equivalent of 7 human years, therefore 9 year old animals are approaching “retirement age” Dogs 80% Cats 20%

17. Introduction CDS Epidemiology Pathology Management Conclusion Crufts Survey of UK Pet Owners - pets over 7 years olds • Questions asked about awareness of problems and treatments as well as clinical signs in their own pet • 93% think that pets should get the same or better medical treatment than themselves • 31% already giving supplements on a daily basis

18. Introduction CDS Epidemiology Pathology Management Conclusion Survey of UK Owners with Pets over 7 years old Compared to when the pets were younger: 60 67 Percent of pets 53 40 44 33 31 20 Sleep Patterns Interaction Disorientation Quality of Life Reduced House Soiling More restless & More confused Less Eager to play & Less Active

19. Introduction CDS Epidemiology Pathology Management Conclusion Survey of UK Owners with Pets over 7 years old However, despite owners being able to see the signs of Cognitive Dysfunction: • Only 7% of owners feel well informed about treatments available for older pet behavioural problems • 46% are unaware that there are any treatments at all As a result of this, they may not see the point in seeking advice. Owners fear that euthanasia would be the only recommendation by the vet if no treatments are available.

20. Introduction CDS Epidemiology Pathology Management Conclusion Survey of UK Owners with Pets over 7 years old • 80% of owners would like more access to information about older pets – 61% would like to attend clinics for older pets • 83% of owners would want advice and treatment of pets diagnosed with age related behavioural disorders

21. Introduction CDS Epidemiology Pathology Management Conclusion Conclusions from UK Survey • Cognitive Dysfunction in the UK seems to effect 30%+ of all pets over 7 years old • The pet owner is noticing the behavioural changes associated with the condition • Many owners are unaware of available treatments for older pet behaviour problems • The vast majority want more information, many willing to attend special vet clinics to help their pets

22. Introduction CDS Epidemiology Pathology Management Conclusion Cat Cognitive Dysfunction • 43% of 152 cats had one or more signs consistent with CDS • After excluding medical cases • 28% of cats aged 11-14 years • 49% of cats aged 15-21 years old Displayed signs consistent with cognitive dysfunction • For instance, • Does the cat continue to use the little box on a regular basis? • Does the cat continue to groom and show interest in household activities?

23. What causes Cognitive Dysfunction?

24. Introduction CDS Epidemiology Pathology Management Conclusion Mitochondrial Energy & Free Radical Production

25. Introduction CDS Epidemiology Pathology Management Conclusion Theory of Age-Related Mental Decline

26. Introduction CDS Epidemiology Pathology Management Conclusion Effect of Age-Related Brain Damage End Result = Loss of Grey and White Matter

27. Introduction CDS Epidemiology Pathology Management Conclusion Patho-physiology of Cognitive Dysfunction • Cummings et al 1998 • Accumulation of β-amyloid deposits in frontal and hippocampus in dogs with increased cognitive dysfunction • Almost identical to Alzheimer disease in humans • Cummings et al 1996 • Degree of β-amyloid deposits in the dog brain was proportional to the degree of impairment in learning complex tasks

28. Introduction CDS Epidemiology Pathology Management Conclusion Patho-physiology of Cognitive Dysfunction • The decline of neuronal grey and white matter in the frontal and cerebral brain • Increase in ventricular volume • Neurotoxic deposits (lipofuscin, ubiquitin and β-amyloid) • Results in • Loss of Memory • Loss of Innate Controls • Bladder • Rectum • Increase in anxiety

29. Introduction CDS Epidemiology Pathology Management Conclusion Effects of Gonadectomy on Cognitive Dysfunction • Human research and laboratory research has shown beneficial effects of oestrogen and testosterone for neuron survival and adaptive growth (Haskell et al 1997; Yaffe et al 1998) • Ovariectomy may predispose women to AD • High correlation with men diagnosed with AD and low levels of free testosterone • Study of aging dogs and cognitive dysfunction: • Intact males only showed mild signs of CD • Neutered males about 50% showed severe stage CD behavioural changes(Hart B.L. JAVMA 2001)

30. Introduction CDS Epidemiology Pathology Management Conclusion CD Diagnostics • Eliminate other possible causes of age-related behavioural changes • Musculoskeletal • Organ failure • Endocrinopathies, i.e. thyroid • Cardiovascular • Simple CBC and biochemistry • Urine tests • Ask appropriate behavioural screening questions (DISHA)

31. Introduction CDS Epidemiology Pathology Management Conclusion Prevention and Treatment of Age-Related Cognitive Dysfunction • Calorific restriction is the only known regimen of life-style change that increases the life-span of animals • Most important aspects to control are: • Maintenance of mitochondrial function • Control of oxidant production • Production of neurotransmitters

32. Introduction CDS Epidemiology Pathology Management Conclusion Prevention and Management of Age-Related Cognitive Dysfunction • Supplementation of diet with specific metabolites: • Metabolic enhancers • Neurotransmitter enhancers • Antioxidant damage preventers • Drugs i.e. L-deprenyl HCl an MAO B inhibitor

33. Introduction CDS Epidemiology Pathology Management Conclusion Management of Cognitive Dysfunction • L-deprenyl HCl (Selegiline) = ameliorates signs of CD in some dogs. • Reduces depletion of dopamine & some neuroprotective and antioxidant support • Numerous drugs contraindicated with its use • Side effects in several different trials • Nicergoline (alpha 1&2 adrenergic antagonist) • Increase cerebral blood flow, enhance neuronal transmission, and have a neuroprotective effect • Propentofylline • Inhibit platelet aggregation and blood flow

34. Introduction CDS Epidemiology Pathology Management Conclusion Supplementation Studies into Reducing Cognitive Dysfunction Symptoms • L-Carnitine and alpha-lipoic acid fed to old rats • Reversed age-related mitochondrial degeneration • Lowered oxidative damage in liver cells • Increased the binding affinity of brain and memory related enzymes (Hageb et al 1998; Liu et al 2002) • 1 year study in old dogs with L-Carnitine, alpha-lipoic acid, and vitamins E and C supplemented • Significantly reduced the impairment that aged dogs showed on difficult discrimination tasks (Milligram et al 2002 and 2005)

35. Introduction CDS Epidemiology Pathology Management Conclusion Supplementation Studies into Reducing Cognitive Dysfunction Symptoms in the Dog • Milligram’s study in Beagles tested three groups: • Behavioural enrichment • Supplementation • Combination of both • Both behavioural enrichment and supplementation reduced age-related decline • The combination had the greater protective effect on learning ability = Synergism

36. Introduction CDS Epidemiology Pathology Management Conclusion Conclusion • Cognitive Dysfunction is recognized as an increasing disorder in the aging pet population • Other age-related diseases need to be ruled out first by a thorough clinical examination • Owners are acutely aware of the change in behaviour of their “older” pets but unaware of viable management and therapeutic options • Owners reluctant to seek veterinary advice for fear of euthanasia being offered • Add behavioural questions to your old pet exams

37. Aktivait – Behavioural Age-related Pet Supplement Thanks Drs. Sarah Heath and Paul Craze plus all the UK vets, nurses and dog owners involved in the Aktivait Trial

38. Canine Cognitive Dysfunction A Nutritional Supplement Trial 1.VetPlus,Lytham St. Anne’s, UK 2 Takamby Consult., Panama St. Stephen Barabás BSc BVMS MRCVS1 Hermann FM Bourgeois DVM2

39. Introduction Material Method Results Discussion Conclusion Effect of Age-Related Brain Damage End Result = Loss of Grey and White Matter

40. Introduction Material Method Results Discussion Conclusion What Causes Canine Cognitive Dysfunction? • Physiological condition • Compromised cerebral blood flow • Depletion in neurotransmitters: dopamine… • Increased levels of free radicals • Behavioral signs “DISH” • D isorientation • I nteraction • S leep Pattern • H ouse Training

41. Introduction Material Method Results Discussion Conclusion Survey at Crufts Dog Show VETPLUS,2005 • n = 981        %

42. Introduction Material Method Results Discussion Conclusion Supplementation Canine CD Trial • Objective: • To assess the therapeutic effect of a nutritional supplement including anti-oxidants in the management of CDD in dogs • Type • Multi-centered • 20 veterinary practices • Geographically dispersed • Duration: 56 days • Placebo controlled • Double-blinded

43. n = 44 Inclusion > 8 years old Owner > 2 m > 1 month “DISH” Haematology OK Biochemistry OK Maintenance diet Exclusion Medical treatments Clinical disease “DISH” prior to 8 yrs Prescription diets Agressivity level < 1 clinical sign of CD Introduction Material Method Results Discussion Conclusion Inclusion: Exclusion Criteria

44. Introduction Material Method Results Discussion Conclusion Combination Supplement

45. Introduction Material Method Results Discussion Conclusion Oxidative Damage to the Neuron HEAD E.,2008 EPA/DHA Phosphotidylserine Phosphotidylserine Acetyl L – Carnitine L – carnitine Co Q10 Co Q10 Vit E, Vit C Selenium N-acety Cysteïne  Lipoic acid Acetyl L-carnitine L – carnitine Co Q10

46. A B 1 2 “exit” baseline 3 Introduction Mateiral Method Results Discussion Conclusion Clinical Methodology -7 0 10 21 28 42 49

47. Introduction Material Method Results Discussion Conclusion Recruitment Criteria: “DISH” • D isorientation • Delay or lack of recognition • people • animals • places • I nteractions •  social interactions • people • animals • other pets •  display of aggressive behavior

48. Introduction Material Method Results Discussion Conclusion Recruitment Criteria: “DISH” • S leep Pattern •  sleep during daytime •  sleep at night •  incidence of restlessness during sleep • H ouse Training •  incidence of house soiling •  inappropriate toileting in a variety of locations •  in sitting at inappropriate doors

49. Introduction Material Method Results Discussion Conclusion Clinical Behaviour Scoring • Referring to baseline – based on differences • Insignificant 0 • Mild 1 • Significant 2 • Moderately severe 3 • Very severe 4 • Semi quantitative • Number of incidents • Global owner evaluation • p < 0.05  statistically significant

50. Introduction Material Method Results Discussion Conclusion Study Data • End of study 27 • Out 17 • Placebo 8 • Supplement 9 • Reasons • Moving • Disrespect of paperwork • Non-relied clinical reasons