Recent developments in Canine Cognitive Dysfunction Syndrome.

Main Article Content

Alejandro Seisdedos Benzal
Alba Galán Rodríguez

Abstract

Canine Cognitive Dysfunction Syndrome (CCD) is a neurodegenerative disease affecting aging dogs. CCD is an underdiagnosed disease that involves at least 14% of geriatric dogs, but apparently less than 2% of diseased dogs are diagnosed. There are several physiopathological similarities between Alzheimer disease (AD) and CCD, developing amyloid-β deposits in brain parenchyma and blood vessels, brain atrophy and neuronal loss. The clinical signs lead to behavioural changes. They are unspecific and could appear as soon as seven years of age, but are more relevant in senior dogs. The abnormal behaviour could be classified following the acronym DISHA: Disorientation in the immediate environment; altered Interactions with humans and other animals; Sleep-wake cycle disturbances; House-soiling; and changes in Activity levels. There is no specific diagnostic test or biomarker to demonstrate the presence of CCD; therefore, it is often assessed by ruling out other diseases that may cause similar behavioural changes. Veterinarians have to be able to make an accurate account of veterinary history asking for abnormal behaviour that could be misreported by the owners. CCD is a neurodegenerative disorder that cannot be cured. It is possible to delay the progression of the clinical signs and improve the quality of life of patients, but like in AD, the progression of the illness will depend on the individual. There are three treatment pathways, which could be used in combination: drug therapy to improve cognition and reduce anxiety, antioxidant diet and nutraceutical supplements to reduce the progression of the illness, and finally, environmental enrichment to maintain brain activity. The aim of this review article is to contribute to the knowledge of the illness, presenting recent advances in the pathophysiology, diagnosis and treatment of the disease.

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Section
Paper reviews
Author Biographies

Alejandro Seisdedos Benzal, University of Córdoba

Department of Animal Medicine and Surgery

Alba Galán Rodríguez, University of Córdoba

Department of Animal Medicine and Surgery

References

Azkona, G., García-Belenguer, S., Chacón, G., Rosado, B., León, M., and Palacio, J. 2009. Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs. Journal of Small Animal Practice 50: 87-91.

Bernardini, M. 2010. Esame neurologico. In Neurologia del Cane e del Gatto, 30-69, ed. M. Bernardini. Milano: Poletto Editore.

Bosch, M.N., Pugliese, M., Andrade, C., Gimeno-Bayón, J., Mahy, N., and Rodríguez, M.J. 2015. Amyloid-β immunotherapy reduces amyloid plaques and astroglial reaction in aged domestic dogs. Neurodegenerative Diseases 15(1): 24-37.

Canudas, J., Insua, D., Sarasa, L., González-Martínez, Á., Suárez, M.L., Santamarina, G., Pesini, P., and Sarasa, M. 2014. Neprelysin is poorly expressed in the prefrontal cortex of aged dogs with canine cognitive dysfunction syndrome. International Journal of Alzheimer´s Disease 2014.

Cummings, B.J., Head, E., Ruehl, W., Milgram, N.W., and Cotman, C.W. 1996. The canine as an animal model of human aging and dementia. Neurobiology of Aging 17: 259-268.

Davis, P.R. and Head, E. 2014. Prevention approaches in a preclinical canine model of Alzheimer´s disease. Frontiers in Pharmacology 5: 47.

De Risio, L. and Platt, S. 2014. Classification of seizures and epilepsies. In Canine and Filine Epilepsy, 39, ed. J. Killick. Croydon, London, United Kingdom: CAB International.

De Risio, L. and Platt, S. 2014. Phenobarbital. In Canine and Filine Epilepsy, 374, ed. J. Killick. Croydon, London, United Kingdom: CAB International.

Dewey, C.W. 2008. Encephalopathies: Disorders of the brain. In A Practical Guide to Canine and Feline Neurology, 115-220, ed. C.W. Dewey. Ames, Iowa: Iowa State University Press.

Dowling, A.L.S. and Head, E. 2012. Antioxidants in the canine model of human aging. Biochimica et Biophysica Acta-Molecular Basis of Disease 1822: 685-689.

Ettinger, S.J. and Feldman E.C. 2010. Endocrine disorders. In Textbook of Veterinary Internal Medicine, 1711-1873, ed S.J. Ettinger and E.C. Feldman. St. Louis, Missouri: Saunders Elsevier.

Ettinger, S.J. and Feldman E.C. 2010. Pathophysiology of Heart Failure. In Textbook of Veterinary Internal Medicine, 1143-1158, ed S.J. Ettinger and E.C. Feldman. St. Louis, Missouri: Saunders Elsevier.

Fast, R., Rodell, A., Gjedde, A., Mouridsen, K., Alstrup, A.K., Bjarkam, C.R., West, M.J., Berendt, M., and Moller, A. 2013. PIB fails to map amyloid deposits in cerebral cortex of aged dogs with canine cognitive dysfunction. Frontiers in Aging Neuroscience 5: article number 99.

Galán, A., Carletti, B.E., Morgaz, J., Granados, M.M., Mesa, I., Navarrete, R., Lombardo, R., Martínez, C.M., and Martín-Suárez, E.M. 2014. Comparative study of select biochemical markers in cerebrospinal fluid of healthy dogs before and after treatment with nutraceuticals. Veterinary Clinical Pathology 43(1): 72-77.

González-Martínez, Á., Rosado, B., Pesini, P., García-Belenguer, S., Palacio, J., Villegas, A., Suárez, M.L., Santamarina, G., and Sarasa, M. 2013. Effect on age and severity of cognitive dysfunction on two simple tasks in pet dogs. The Veterinary Journal 198: 176-181.

Grubb, T. 2010. Chronic neuropathic pain in veterinary patients. Topics in Companion Animal Medicine 25(1): 45-52.

Hartlage-Rübsamen, M., Morawski, M., Waniek, A., Jäger, C., Zeitschel, U., Koch, B., Cynis, H., Schilling, S., Schliebs, R., Demuth, H.U., and Robner, S. 2011. Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aβ deposits in hippocampus via distinct cellular mechanisms. Acta Neuropathologica 121: 709-719.

Head, E. 2002. Brain Aging in Dog: parallels with human brain aging and Alzheimer’s disease. Journal of Veterinary Pharmacology and Therapeutics 2(3): 247-260.

Head, E. 2008. Oxidative damage and cognitive dysfunction: antioxidant treatments to promote healthy brain aging. Neurochemical Research 34(4): 670-678.

Heath, S.E., Barabas, S., and Craze, P.G. 2007. Nutritional supplementation in cases of canine cognitive dysfunction-a clinical trial. Applied Animal Behaviour Science 105: 274–83.

Inagawa, K., Seki, S., Bannai, M., Takeuchi, Y., Mori, Y., and Takahashi, M. 2005. Alleviate effects of γ-aminobutyric acid on behavioural abnormalities in aged dogs. The Journal of Veterinary Medical Science 67(10): 1063-1066.

Iwata, N., Higuchi, M., and Saido, T.C. 2005. Metabolism of amyloid-β peptide and Alzheimer´s disease. Pharmacology and Therapeutics 108: 129-148.

Jaggy, A. 2010. Behavioural problems and abnormal behaviour. In Small Animal Neurology, 467-489, ed. A. Jaggy. Germany: Schlütersche.

Laflamme, D.P. 2012. Nutritional care for aging cats and dogs. Veterinary Clinics of North America-Small Animal Practice 42: 769-791.

Landsberg, G. 2005. Therapeutics agents for the treatment of cognitive dysfunction syndrome in senior dogs. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29: 471-479.

Landsberg, G., DePorter, T., and Araujo, J.A. 2011. Clinical signs and management of anxiety, sleeplessness and cognitive dysfunction in the senior pet. Veterinary Clinics of North America-Small Animal Practice 41: 565-590.

Landsberg, G., Hunthausen, W., and Ackerman, L. 2013. Appendix D Drug dosages. In Behaviour Problems of the Dog and Cat, 415-422, ed. R. Edwards. China: Saunders Elsevier.

Landsberg, G.M., Nichol, J., and Araujo, J.A. 2012. Cognitive dysfunction syndrome. A disease of canine and feline brain aging. Veterinary Clinics of North America-Small Animal Practice 42: 749-768.

Manteca, X. 2011. Nutrition and behavior in senior dogs. Topics in Companion Animal Medicine 26: 33-36.

Mariotti, V.M., Landucci, M., Lippi, I., Amat, M., Manteca, X. and Guidi, G. 2009. Epidemiological study of behavioural disorders in elderly dogs [abstract]. In Proceedings 7th International Meeting of Veterinary Behaviour Medicine, 241-243, ed. S. E. Heath. Belgium: European Society of Veterinary Clinical Ethology.

Martin, S.B., Cenini, G., Barone, E., Dowling, A.L.S., Mancuso, C., Butterfield, D.A., Murphy, M.P., and Head, E. 2011. Coenzyme Q10 and cognition in atorvastatin treated dogs. Neurosciences Letters 501: 92-95.

Milgram, N.W., Landsberg, G.M. and Visnesky, M. 2011. Effect of apoaequroin on cognitive function in aged canines. Paper presented at the 17th Congress of ESVCE “Social communications in companion animals” and 1st Annual Congress of ECAWBM, Avignon, France, November 25-26, 2011.

Nagasawa, M., Shimozawa, A., Mogi, K., and Kikusui, T. 2014. N-acetyl-D-mannosamine treatment alleviates age-related decline in place learning ability in dogs. Journal of Veterinary Medical Science 76: 757-761.

Nelson, R.W. and Couto C.G. 2009. Clinical manifestations of hepatobiliary disease. In Small Animal Internal Medicine, 485-495, ed. R.W. Nelson, C.G. Couto. St, Louis, Missouri: Mosby Elsevier.

Nelson, R.W. and Couto C.G. 2009. Clinical manifestations of urinary disorders. In Small Animal Internal Medicine, 607-622, ed. R.W. Nelson, C.G. Couto. St, Louis, Missouri: Mosby Elsevier.

Nelson, R.W. and Couto C.G. 2009. Disorders of the joints. In Small Animal Internal Medicine, 1127-1141, ed. R.W. Nelson, C.G. Couto. St, Louis, Missouri: Mosby Elsevier.

Nielson, J.C., Hart, B.L., Cliff, K.D., and Ruehl, W.W. 2001. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. Journal of the American Veterinary Medical Association 218: 1787-1791

Pan, Y., Larson, B., Araujo, J.A., Lau, W., De Rivera, C., Santana, R., Gore, A., and Milgram, N.W. 2010. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. British Journal of Nutrition 103: 1746–1754.

Pan, Y. 2011. Enhancing brain function in senior dogs: a new nutritional approach. Topics in Companion Animal Medicine 26: 10-16.

Pugliese, M., Gangitano, C., Ceccariglia, S., Carrasco, J.L., Del Fa, A., Rodríguez, M.J., Michetti, F., Mascort, J., and Mahy, N. 2007. Canine cognitive dysfunction and the cerebellum: acetylcholinesterase reduction, neuronal and glial changes. Brain Research 1139: 85–94.

Reilly, C.E. 2001. Neprilysin content is reduced in Alzheimer brain areas. Journal of Neurology 248: 159-160.

Romanucci, M. and Della Salda, L. 2015. Oxydative stress and protein quality control systems in the aged canine brain as a model for human neurodegenerative disorders. Oxidative Medicine and Cellular Longevity 2015.

Salvin, H.E., McGreevy, P.D., Sachev, P.S., and Valenzuela, M.J. 2006. Under diagnosis of canine cognitive dysfunction; a cross-sectional survey of older companion dogs. Veterinary Journal 184: 277-281.

Schmidt, F., Boltze, J., Jäger, C., Hofmann S., Willems, N., Seeger, J., Härtig, W., and Stolzing, A. 2015. Detection and quantification of β-amyloid, pyroglutamil Aβ, and tau in aged canines. Journal of Neuropathology and Experimental Neurology 74: 912-923.

Siwak-Tapp, C.T., Head, E., Muggenburg, B.A., Milgram, N.W., and Cotman, C.V. 2007. Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function. Neurobiology of Learning and Memory 88(2): 249–259.

Taha, A.Y., Henderson, S.T., and Burnham, W.M. 2009. Dietary enrichment with medium chaintriglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs; implications for treating age-related cognitive decline. Neurochemical Research 34(9): 1619–1625.

Vite, C.H. and Head, E. 2014. Aging in the canine and feline brain. Veterinary Clinics of North America-Small Animal Practice 44: 1113-1129.